US2015099730A1PendingUtilityA1
Imidazolin-5-one derivative useful as fasn inhibitors for the treatment of cancer
Est. expirySep 7, 2032(~6.2 yrs left)· nominal 20-yr term from priority
Inventors:Peter J. Connolly
A61P 3/06A61P 35/00A61P 3/10A61P 5/00A61P 43/00C07D 487/10C07D 471/04A61P 3/04C07D 413/14C07D 403/14C07D 417/14C07D 471/10C07D 498/04C07D 409/14C07D 405/14C07D 401/14C07D 403/06C07D 401/06C07D 491/107
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Claims
Abstract
Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including those mediated by inhibition of fatty acid synthase (FASN) enzyme, such as, cancer, obesity or related discorders, and liver related disorders. Such compounds are represented by formula (I) as follows: wherein L 1 , a, b, m, n, R 1 , R 2 , R 3 , R 4 , and R 5 are defined herein.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I)
wherein
R 1 and R 2 are taken together with the carbon atom to which they are bound to form an optionally substituted ring structure selected from the group consisting of
(a) C 3-8 cycloalkyl; wherein the C 3-8 cycloalkyl is optionally substituted with one to two R 11 groups;
(b) benzo-fused C 5-6 cycloalkyl; wherein the benzo-fused C 5-6 cycloalkyl is bound through a carbon atom of the C 5-6 cycloalkyl portion of the ring structure; wherein the benzo-fused C 5-6 cycloalkyl is optionally substituted with one to two R 11 groups; and
(c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to 8-membered, saturated heterocyclyl contains one heteroatom selected from the group consisting of O, S and N; wherein the S is optionally substituted with one to two oxo; wherein the N is substituted with R 10 ; provided that the heteroatom is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 8-membered, saturated heterocyclyl is optionally substituted with one R 11 group, and further optionally substituted with one R 12 group;
wherein R 10 is selected from the group consisting of hydrogen, C 1-4 alkyl, fluorinated C 1-4 alkyl, —CH 2 -(hydroxy substituted C 1-4 alkyl), —(C 2-4 alkyl)-O-(C 1-4 alkyl), —(C 2-4 alkenyl), —(C 1-4 alkyl)-phenyl, —C(O)—NR A R B , —C(O)—(C 1-3 alkyl)-NR A R B , —C(O)—(C 1-4 alkyl), —C(O)-(fluorinated C 1-2 alkyl), —C(O)—(C 3-6 cycloalkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered heteroaryl),
—C(O)O—(C 1-4 alkyl), —SO 2 —(C 1-4 alkyl), —SO 2 —NR A R B , phenyl, and 5 to 6-membered heteroaryl;
wherein Z 1 is selected from the group consisting of —CH 2 —, —O—, —N(R C )—, —S—, —S(O)— and —SO 2 —; wherein R A , R B and R C are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or as part of a substituent group, is further optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, NR A R B , C 1-4 alkyl, fluorinated C 1-4 alkyl, C 1-4 alkoxy, and fluorinated C 1-4 alkoxy;
wherein each R 11 is independently selected from the group consisting of hydroxy, oxo, halogen, C 1-4 alkyl, fluorinated C 1-4 alkyl, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, hydroxy substituted C 1-4 alkyl, -(C 1-4 alkyl)-O-(C 1-4 alkyl), -(C 1-4 alkyl)-phenyl, -cyano, —NR D R E , —C(O)—NR D R E , —C(O)—(C 1-4 alkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered heteroaryl),
—C(O)OH, —C(O)O—(C 1-4 alkyl), —SO 2 —(C 1-4 alkyl), —SO 2 —NR D R E , phenyl and, 5 to 6-membered heteroaryl;
wherein Z 2 is selected from the group consisting of —CH 2 —, —O—, —N(R C )—, —S—, —S(O)— and —SO 2 —; wherein R D , R E and R F are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or as part of a substituent group, is further optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, NR D R E , C 1-4 alkyl, fluorinated C 1-4 alkyl, C 1-4 alkoxy, and fluorinated C 1-4 alkoxy;
and wherein R 12 is selected from the group consisting of hydroxy, oxo, halogen, C 1-4 alkyl, fluorinated C 1-4 alkyl, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, and hydroxy substituted C 1-4 alkyl;
m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2, then m is 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl, piperidin-2S-yl, and piperidin-4-yl;
a is an integer from 0 to 1;
L 1 is selected from the group consisting of —C(O)—, —C(O)O—, —C(O)—NR E —, —C(S)—, —SO 2 —, and —SO 2 —NR L —; wherein R E is selected from the group consisting of hydrogen and C 1-4 alkyl;
R 3 is selected from the group consisting of C 1-4 alkyl, fluorinated C 1-4 alkyl, hydroxy substituted C 1-4 alkyl, C 2-4 alkenyl, C 3-6 cycloalkyl, —(C 1-4 alkyl)-(C 3-6 cycloalkyl), 4 to 6-membered, saturated heterocyclyl, —(C 1-4 alkyl)-(4 to 6-membered, saturated heterocyclyl), —(C 2-4 alkenyl)-(5 to 6-membered, saturated heterocyclyl), 5 to 6-membered heteroaryl, —(C 1-4 alkyl)-(5 to 6-membered heteroaryl), —(C 2-4 alkenyl)-(5 to 6-membered heteroaryl), and NR V R W ; wherein R V and R W are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
wherein the C 3-6 cycloalkyl, 4 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C 1-4 alkyl, fluorinated C 1-4 alkyl, —(C 1-4 alkyl)-OH, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, and NR G R H ; wherein R G and R H are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
is selected from the group consisting of
b is an integer from 0 to 2;
each R 4 is independently selected from the group consisting of hydroxy, halogen, C 1-4 alkyl, fluorinated C 1-4 alkyl, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, cyano, and NR J R K ; wherein R J and R K are each independently selected from the group consisting of hydrogen and C 1-4 alkyl; provided that each R 4 group is bound to a carbon atom;
provided that when
is selected from the group consisting of
and substituted with —(R 4 ) b , then b is an integer from 0 to 1;
R 5 is selected from the group consisting of
selected from the group consisting of aryl, heteroaryl, and partially unsaturated heterocyclyl;
c is an integer from 0 to 2;
each R 6 is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, nitro, C 1-4 alkyl, fluorinated C 1-4 alkyl, hydroxy substituted C 1-4 alkyl, —(C 1-4 alkyl)-CN, —(C 1-4 alkyl)-O—(C 1-4 alkyl), C 1-4 alkoxy, fluorinated C 1-4 alkoxy, —SO 2 —(C 1-4 alkyl), —NR M R N , —(C 1-4 alkyl)-NR P R Q , —C(O)—(C 1-4 alkyl), —C(O)-(fluorinated C 1-2 alkyl), —C(O)—NR M R N , —C(O)OH, —C(O)O—(C 1-4 alkyl), —NR M —C(O)H, —NR M —C(O)—(C 1-4 alkyl), —NR M —SO 2 —(C 1-4 alkyl), C 3-6 cycloalkyl, -cyano-(C 3-6 cycloalkyl), —(C 1-4 alkyl)-(C 3-6 cycloalkyl), —S—(C 3-6 cycloalkyl), —SO—(C 3-6 cycloalkyl), —SO 2 —(C 3-6 cycloalkyl), —NH—(C 3 -6 cycloalkyl), —NH—SO 2 —(C 3-6 cyclalkyl), oxetanyl, —(C 1-2 alkyl)-oxetanyl, tetrahydofuranyl, —(C 1-2 alkyl)-tetrahydro-furanyl, tetrahydro-pyranyl, and —(C 1-2 alkyl)-tetrahydro-pyranyl;
wherein R M and R N are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
wherein R P and R Q are each independently selected from the group consisting of hydrogen and C 1-4 alkyl; alternatively R P and R Q are taken together with the nitrogen atom to which they are bound to form a 5 to 6-membered saturated heterocyclyl; such 5 to 6-membered saturated heterocyclyl is optionally substituted with a substituent selected from the group consisting of halogen, C 1-4 alkyl, and fluorinated C 1-4 alkyl;
wherein selected from the group consisting of phenyl and 5 to 6-membered heteroaryl;
d is an integer from 0 to 1;
R 7 is selected from the group consisting of hydroxy, halogen, cyano, nitro, C 1-4 alkyl, fluorinated C 1-4 alkyl, hydroxy substituted C 1-4 alkyl, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, —NR R R S , —C(O)—NR R R S , —C(O)OH and —C(O)O—(C 1-4 alkyl); wherein R R and R S are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
wherein
is selected from the group consisting of phenyl, 5 to 6-membered saturated heterocyclyl and 5 to 6-membered heteroaryl;
e is an integer from 0 to 2;
each R 8 is independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C 1-4 alkyl, fluorinated C 1-4 alkyl, hydroxy substituted C 1-4 alkyl, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, —NR T R U , —C(O)—NR T R U , —C(O)OH, —C(O)O—(C 1 -4 alkyl), —(C 1 -4 alkyl)-NR T R U , C 3-5 cycloalkyl, —(C 1-2 alkyl)-(C 3-5 cycloalkyl), oxetanyl, —(C 1-2 alkyl)-oxetanyl, tetrahydofuranyl, —(C 1-2 alkyl)-tetrahydro-furanyl, tetrahydro-pyranyl, and —(C 1-2 alkyl)-tetrahydro-pyranyl; wherein R T and R U are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
provided that when
is a 5-membered heteroaryl, then
is bound at the 3-position, relative to the point of attachment of the
to the
provided further than when
is phenyl or a 6-membered heteroaryl, then
is bound at the 3- or 4-position, relative to the point of attachment of the
to the
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)—CF 3 , —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH 3 or —SO 2 —CH 3 ,
and b=0; then R 5 is other than quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl) and 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl and 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —SO 2 -pyrrolidin-1-yl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than benzofuran-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-pyridin-3-yl;
(R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,
is piperidin-3R-yl or piperidin-3S-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than of indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,
is piperidin-4-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl or 4-(1-methyl-pyrazol-4-yl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF 3 , —C(O)OCH 3 , and —SO 2 —CH 3 ;
and b=0; then R 5 is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
2 . A compound as in claim 1 , wherein
R 1 and R 2 are taken together to form an optionally substituted ring structure selected from the group consisting of (a) C 3-6 cycloalkyl; wherein the C 3-8 cycloalkyl is optionally substituted with one R 11 group; (b) benzo-fused C 5-6 cycloalkyl; wherein the benzo-fused C 5-6 cycloalkyl is bound through a carbon atom of the C 5-6 cycloalkyl portion of the ring structure; and wherein the benzo-fused C 5-6 cycloalkyl is optionally substituted with one R 11 group; and (c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered, saturated heterocyclyl contains O or NR 10 ; provided that the O or NR 10 is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 6-membered, saturated heterocyclyl containing the O or NR 10 is optionally substituted with one R 11 group and further optionally substituted with one R 12 ; wherein R 10 is selected from the group consisting of hydrogen, C 1-4 alkyl, fluorinated C 1-4 alkyl, —CH 2 -(hydroxy substituted C 1-4 alkyl), —(C 2-4 alkenyl), —(C 1-4 alkyl)-phenyl, —(C 2 alkyl)-O-(C 1-4 alkyl), —C(O)O—(C 1-4 alkyl), —C(O)—(C 1-4 alkyl), —C(O)-(fluorinated C 1-2 alkyl), —C(O)—(C 3-6 cycloalkyl),
—C(O)—NR A R B , and —SO 2 —(C 1-2 alkyl); wherein Z 1 is selected from the group consisting of —CH 2 —, —O—, and —N(R C )—; and wherein R A , R B and R C are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
wherein R 11 is independently selected from the group consisting of hydroxy, oxo, halogen, C 1-4 alkyl, fluorinated C 1-4 alkyl, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, hydroxy substituted C 1-4 alkyl, —(C 1-4 alkyl)-phenyl, -cyano, —NR D R E , —C(O)—NR D R E , —C(O)—(C 1-4 alkyl), —C(O)OH, and —C(O)O—(C 1-4 alkyl);
wherein R 12 is selected from the group consisting of hydroxy, oxo, halogen, C 1-2 alkyl, CF 3 , C 1-2 alkoxy, —OCF 3 , and hydroxy substituted C 1-2 alkyl;
m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2, then m is 0;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3S-yl, piperidin-3R-yl, and and piperidin-4-yl;
a is 1;
L 1 is selected from the group consisting of —C(O)—, —C(O)O—, —C(O)—NR L , and —SO 2 —; wherein R L is selected from the group consisting of hydrogen and methyl;
R 3 is selected from the group consisting of C 1-4 alkyl, fluorinated C 1-2 alkyl, hydroxy substituted C 1-4 alkyl, C 2-4 alkenyl, C 3-6 cycloalkyl, 4 to 6-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl and NR V R W ; wherein R V and R W are each independently selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein the C 3-6 cycloalkyl, 4 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C 1-4 alkyl, fluorinated C 1-4 alkyl, —(C 1-2 alkyl)-OH, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, and NR G R H ; wherein R G and R H are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
is selected from the group consisting of
b is an integer from 0 to 1;
R 4 is selected from the group consisting of, halogen, C 1-4 alkyl, fluorinated C 1-4 alkyl, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, and NR J R K ; wherein R J and R K are each independently selected from the group consisting of hydrogen and C 1-2 alkyl; provided that the R 4 group is bound to a carbon atom;
R 5 is selected from the group consisting of
selected from the group consisting of aryl, heteroaryl and partially unsaturated heterocyclyl;
c is an integer from 0 to 2;
each R 6 is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, nitro, C 1-4 alkyl, fluorinated C 1-4 alkyl, hydroxy substituted C 1-4 alkyl, cyano substituted (C 1-4 alkyl), —(C 1-2 alkyl)-O—(C 1-4 alkyl), C 1-4 alkoxy, fluorinated C 1-4 alkoxy, —SO 2 —(C 1-4 alkyl), —C(O)—(C 1-4 alkyl), —C(O)-(fluorinated C 1-2 alkyl), —C(O)OH, —C(O)O—(C 1-4 alkyl), —C(O)—NR M R N , —NR M R N , —NR M —C(O)H, —NR M —SO 2 —(C 1-4 alkyl), C 3-5 cyclo alkyl, 1-cyano-(C 3-5 cyclo alkyl), -(C 1-2 alkyl)-(C 3-5 cycloalkyl), —S—(C 3-5 cycloalkyl), —SO 2 —(C 3-5 cycloalkyl), —NH—(C 3-5 cycloalkyl), —NH—SO 2 —(C 3-5 cycloalkyl), oxetanyl, and tetrahydro-furanyl;
wherein R M and R N are each independently selected from the group consisting of hydrogen and C 1-4 alkyl; wherein
is selected from the group consisting of phenyl and 5 to 6-membered heteroaryl;
d is an integer from 0 to 1;
R 7 is selected from the group consisting of hydroxy, halogen, cyano, C 1-4 alkyl, fluorinated C 1-4 alkyl, hydroxy substituted C 1-4 alkyl, C 1-4 alkoxy, and fluorinated C 1-4 alkoxy;
wherein
is selected from the group consisting of phenyl, 5 to 6-membered saturated heterocyclyl and 5 to 6-membered heteroaryl;
e is an integer from 0 to 2;
each R 8 is independently selected from the group consisting of hydroxy, halogen, cyano, C 1-4 alkyl, fluorinated C 1-4 alkyl, hydroxy substituted C 1-4 alkyl, C 1-4 alkoxy, fluorinated C 1-4 alkoxy, —NR T R U , —C(O)—NR T R U , —C(O)OH, —C(O)O—(C 1-4 alkyl), —(C 1-4 alkyl)-NR T R U , C 3-5 cycloalkyl, —(C 1-2 alkyl)-(C 3-5 cycloalkyl), oxetanyl, and tetrahydro-furanyl; wherein R T and R U are each independently selected from the group consisting of hydrogen and C 1-4 alkyl;
provided that when
is a 5-membered heteroaryl, then
is bound at the 3-position, relative to the point of attachment of the
to the
provided further than when
is phenyl or a 6-membered heteroaryl, then
is bound at the 3- or 4-position, relative to the point of attachment of the
to the
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)—CF 3 , —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH 3 and —SO 2 —CH 3 ,
and b=0; then R 5 is other quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl), or 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl, and 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —SO 2 -pyrrolidin-1-yl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than benzofuran-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-pyridin-3-yl;
(R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,
is piperidin-3R-yl or piperidin-3S-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,
is piperidin-4-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF 3 , —C(O)OCH 3 , and —SO 2 —CH 3 ;
and b=0; then R 5 is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
3 . A compound as in claim 2 , wherein
R 1 and R 2 are taken together to form an optionally substituted ring structure selected from the group consisting of C 3-6 cycloalkyl and 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered saturated heterocyclyl contains Ne; provided that the NR 1 ° is not present at the 2-position relative to the carbon atom of the imidazolidin-5-one; wherein R 10 is selected from the group consisting of hydrogen, C 1-4 alkyl, C 2-4 alkenyl, —CH 2 -(hydroxy substituted C 1-2 alkyl), —CH 2 -(phenyl), —(C 2 alkyl)-O—(C 1-2 alkyl), —C(O)—(C 1-4 alkyl), —C(O)-(fluorinated C 1-2 alkyl), —C(O)-(cyclopropyl), —C(O)O—(C 1-4 alkyl), —C(O)—NR A R B , and —SO 2 —(C 1-2 alkyl), wherein R A and R B are each independently selected from the group consisting of hydrogen and methyl; m is an integer from 0 to 1; and n is an integer from 0 to 2 provide that when n is 2, then m is 0
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl, piperidin-3S-yl, and piperidin-4-yl;
a is 1;
L 1 is selected from the group consisting of —C(O)—, —C(O)O—, and —SO 2 —;
R 3 is selected from the group consisting of C 1-4 alkyl, hydroxy substituted C 1-4 alkyl, fluorinated C 1-2 alkyl, C 2-4 alkenyl, C 3-5 cycloalkyl, 4 to 5-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl, and NR V R W ; wherein the C 3-5 cycloalkyl, 4 to 5-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl are each optionally substituted with a substituent selected from the group consisting of halogen, hydroxy, C 1-2 alkyl, (C 1-2 alkyl)-OH, fluorinated C 1-2 alkyl, cyano, and NH 2 ; and wherein R V and R W are each independently selected from the group consisting of hydrogen and methyl;
is selected from the group consisting of
b is an integer from 0 to 1;
R 4 is selected from the group consisting of halogen, C 1-2 alkyl, and C 1-2 alkoxy;
R 5 is selected from the group consisting of
selected from the group consisting of phenyl, naphthyl, 5 to 6-membered heteroaryl, 9 to 10-membered heteroaryl, and partially unsaturated 9 to 10-membered heterocyclyl;
c is an integer from 0 to 2;
each R 6 is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, C 1-4 alkyl, fluorinated C 1-2 alkyl, hydroxy substituted C 1-4 alkyl, cyano-substituted C 1-2 alkyl, —(C 1-2 alkyl)-O—(C 1-2 alkyl), C 1-4 alkoxy, fluorinated C 1-2 alkoxy, —SO 2 —(C 1-4 alkyl), —CO 2 H, —C(O)O—(C 1-2 alkyl), —C(O)—(C 1-2 alkyl), —C(O)-(fluorinated C 1-2 alkyl), —C(O)—NR M R N , —NR M R N , —NR M —C(O)H, —NR M —SO 2 —(C 1-2 alkyl), C 3-5 cycloalkyl, 1-cyano-cyclopropyl, —(C 1-2 alkyl)-(C 3-5 cycloalkyl), —S—(C 3-5 cycloalkyl), —SO 2 —(C 3-5 cycloalkyl), —NH—C(O)—(C 3-5 cycloalkyl) —NH—SO 2 —(C 3-5 cycloalkyl), and oxetan-3-yl; and wherein R M and R N are each independently selected from the group consisting of hydrogen and C 1-2 alkyl;
wherein
is selected from the group consisting of phenyl and 6-membered, nitrogen containing heteroaryl;
wherein
is selected from the group consisting of phenyl, 5 to 6-membered, saturated, nitrogen containing heterocylyl and 5 to 6-membered, nitrogen containing heteroaryl;
e is an integer from 0 to 1;
R 8 is selected from the group consisting of halogen, C 1-4 alkyl, C 3-5 cycloalkyl, —(C 1-2 alkyl)-(C 3-5 cycloalkyl), and oxetanyl;
provided that the
is bound at the 3- or 4-position of the
relative to the point of attachment of the
to the
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)—CF 3 , —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH 3 , and —SO 2 —CH 3 ,
and b=0; then R 5 is other than quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl), or 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl, or 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —SO 2 -pyrrolidin-1-yl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than benzofuran-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-pyridin-3-yl;
(R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,
is piperidin-3R-yl or piperidin-3S-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,
is piperidin-4-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF 3 , —C(O)OCH 3 and —SO 2 —CH 3 ;
and b=0; then R 5 is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
4 . A compound as in claim 3 , wherein
R 1 and R 2 are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(ethenyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(methyl-sulfonyl)-piperidin-4,4-diyl, 1-(2-methoxy-ethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, tetrahydro-pyran-4,4-diyl, tetrahydro-furan-3,3-diyl, and 1-(methoxycarbonyl)-azetidin-3,3-diyl; m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2 then m is 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3R-yl, piperidin-3S-yl, and piperidin-4-yl;
a is 1;
L 1 is selected from the group consisting of —C(O)—, —C(O)O— and —SO 2 —;
R 3 is selected from the group consisting of methyl, ethyl, isopropyl, 1-hydroxyethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 2-hydroxy-propan-2-yl. 3-hydroxy-2-methyl-propan-2-yl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, amino, dimethylamino, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, thiazol-2-yl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, oxetan-2-yl, oxetan-3-yl, 3-methyl-oxetan-3-yl, and pyridin-3-yl;
is selected from the group consisting of
b is an integer from 0 to 1;
R 4 is selected from the group consisting of 2-fluoro, 3-fluoro, 2-chloro, 3-chloro, 2-methyl, 3-methyl, and 2-methoxy;
R 5 is selected from the group consisting of
is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl, 2-fluoro-4-(1-cyano-cuclopropyl)-phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl, 4-(methylcarbonyl)-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-amino-4-hydroxy-phenyl, 3-formamido-4-hydroxy-phenyl 3-(cyclopropylthio)-phenyl, 3-(cyclopropylsulfonyl)-phenyl, 3-(cyclopropylcarbonyl-amino)-phenyl, 3-(cyclopropylsulfonyl-amino)-phenyl, 3-(methylsulfonyl)-phenyl, 3-(isopropylsulfonyl)-phenyl, 3-(aminocarbonyl)-phenyl, 3-carboxy-phenyl, 3-(methoxycarbonyl)-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropyloxy-naphth-2-yl, 2-cyano-naphth-7-yl, 6-cyano-naphth-2-yl, 7-cyano-naphth-2-yl, 5-methoxy-naphth-2-yl, 7-methoxy-naphth-2-yl, 1,5-naphthyridin-3-yl, 1,8-naphthyridin-2-yl, 1,8-naphthyridin-3-yl, chroman-6-yl, isochroman-6-yl, isochroman-7-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 6-isopropyl-pyridin-3-yl, 6-n-propyl-pyridin-3-yl, 5-bromo-pyridin-2-yl, 5-chloro-pyridin-3-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 6-cycloprpoyl-pyridin-3-yl, 6-(1-cyano-cyclopropyl)-pyridin-3-yl, 2-amino-pyrid-4-yl, 5-amino-pyridin-3-yl, 6-amino-pyridin-2-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, 1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, 1-(trifluoromethyl-carbonyl)-indol-5-yl, 2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl, 3-chloro-quinolin-7-yl, 4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 7-bromo-quinolin-2-yl, 2-hydroxy-quinolin-3-yl, 2-cyano-quinolin-6-yl, 2-cyano-quinolin-7-yl, 6-cyano-quinolin-2-yl, 2-methyl-quinolin-5-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-7-yl, 4-methyl-quinolin-7-yl, 2,4-dimethyl-quinolin-7-yl, 2-chloro-3-methyl-quinolin-7-yl, 2-chloro-4-methyl-quinolin-7-yl, 2-methyl-8-fluoro-quinolin-2-yl, 2-methyl-quinolin-7-yl, 2-methyl-7-bromo-quinolin-7-yl, 3-methyl-7-bromo-quinolin-7-yl, 2-methyl-4-chloro-quinolin-7-yl, 4-methyl-7-bromo-quinolin-2-yl, 2-trifluoromethyl-quinolin-7-yl, 2-oxo-quinolin-7-yl, 2-carboxy-quinolin-7-yl, 2-aminocarbonyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl, 3-fluoro-isoquinolin-6-yl, 6-bromo-isoquinolin-3-yl, 1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazlin-7-yl, quinoxalin-6-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 4-chloro-indazol-5-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl, 2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl, 1,4-dimethyl-indazol-5-yl, 1,7-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 2-ethyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 2-isopropyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl, 1-(2-hydroxyethyl)-6-fluoro-indazol-5-yl, 2-(2-hydroxyethyl)-6-fluoro-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-5-yl, 1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-7-methoxymethyl-indazol-4-yl, 1-methyl-3-hydroxymethyl-indazol-5-yl, 1-methyl-3-hydroxymethyl-indazol-6-yl, 1-methyl-7-hydroxymethyl-indazol-4-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, 2-methyl-3-cyano-indazol-5-yl, 2-methyl-3-hydroxymethyl-indazol-5-yl, 2-methyl-3-methoxymethyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl), 1-(2-cyanoethyl)-indazol-5-yl, 2-(2-cyanoethyl)-indazol-5-yl, 1-oxetan-3-yl-indazol-5-yl, 1-cyclopropyl-indazol-5-yl, 1-cyclopropylmethyl-indazol-5-yl, 2-cyclopropylmethyl-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzimidazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-2-yl, 1,2-dimethyl-benzimidazol-6-yl, 1-methyl-6-fluoro-benzimidazol-2-yl, 2-oxo-benzimidazol-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzisoxazol-5-yl, benzthiazol-2-yl, benzthiazol-5-yl, 5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl, 5-chloro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl, 6-methyl-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 5-cyano-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl, 2,3-dihydro-benzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, 1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydrobenzofuran-5-yl, 1,2-dimethyl-1,2-dihydro-3-oxo-indazol-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl, pyrrolo[2,3-b]pyridin-5-yl, 1-methyl-pyrazolo[4,3-b]pyridin-5-yl, [1,2,4]triazo[4,3-a]pyridin-6-yl, 3-methyl-[1,2,4]triazo[4,3-a]pyridin-6-yl, and 4-methyl-3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl;
is selected from the group consisting of phenyl, pyridin-3-yl, and pyridin-4-yl;
and
is selected from the group consisting of 4-bromo-phenyl, 3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, 1-isopropyl-pyrazol-4-yl, 1-isobutyl-pyrazol-5-yl, 1-(2-methylpropyl)-pyrazol-3-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-cyclopropylmethyl-pyrazol-3-yl, 1-cyclopropylmethyl-pyrazol-5-yl, 1,2,3,4-tetrazol-5-yl, pyrazol-3-yl, pyrrolidin-1-yl, morpholin-4-yl, 4-methyl-piperazin-1-yl, imidazol-1-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, and 1-(oxetan-3-yl)-pyrazol-4-yl;
provided that when
is phenyl or pyridin-3-yl, then
is bound to
at the 4-position, relative to the point of attachment of the
to the
provided further that when
is pyridin-4-yl, then
is bound to
at the 3-position, relative to the point of attachment of the
to the
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)—CF 3 , —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH 3 , and —SO 2 —CH 3 ,
and b=0; then R 5 is other than quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2, 3,4,4a, 8a-hexahydro -2-methyl-carbonyl-isoquinolin-6-yl, or 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl, or 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —SO 2 -pyrrolidin-1-yl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than benzofuran-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-pyridin-3-yl;
(R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,
is piperidin-3R-yl or piperidin-3S-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,
is piperidin-4-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl or 4-(1-methyl-pyrazol-4-yl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF 3 , —C(O)OCH 3 , and —SO 2 —CH 3 ;
and b=0; then R 5 is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
5 . A compound as in claim 4 , wherein
R 1 and R 2 are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(ethenylcarbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(methylsulfonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl, tetrahyrdofuran-3,3-diyl, and tetrahydro-pyran-4,4-diyl; m is an integer from 0 to 1; and n is an integer from 0 to 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, and piperidin-4-yl;
a is 1;
L 1 is —C(O)—;
R 3 is selected from the group consisting of ethyl, 1-hydroxy-ethyl, isopropyl, 2-hydroxy-propan-2-yl, 3-hydroxy-2-methyl-propan-2-yl, 2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, oxetan-2-yl, oxetan-3yl, 3-methyl-oxetan-3-yl, tetrahydro-furan-2yl, tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl, and dimethylamino;
b is an integer from 0 to 1;
R 4 is selected from the group consisting of 2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro, and 3-methyl;
R 5 is
is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-aminocarbonyl-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl, 3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl, 3-(cyclopropyl-sulfonyl)-phenyl, naphtha-2-yl, 6-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 5-methoxy-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropoxy-naphth-2-yl, 6-cyano-naphth-2-yl, 7-methoxy-naphth-2-yl, 7-cyano-naphth-2-yl, 6-amino-pyridin-2-yl, isochroman-6-yl, isochroman-7-yl, 2-oxo-indolin-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl-indol-5-yl), 3-cyanomethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl, 4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 3-chloro-quinolin-7-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-6-yl, 4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, 2-chloro-3-methyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 3-fluoro-isoquinolin-6-yl, 1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl, 1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl, 2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl, 1,4-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-3-hydroxymethyl-indazol-5-yl, 1-methyl-3-hydroxymethyl-indazol-6-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, 1-(cyclopropylmethyl)-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzimidazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, 2-oxo-benzimidazol-5-yl, benzothiazol-2-yl, benzthiazol-5-yl, 5-chloro-benzothiazol-2-yl, 5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl, 5-cyano-benzothiazol-2-yl, 6-cyano-benzthiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl, 2,3-dihydrobenzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl, 1,8-naphthyridin-2-yl, and pyrrolo[2,3-b]pyridin-5-yl;
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than quinolin-7-yl, benzofuran-5-yl or 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl, and indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-pyridin-3-yl;
(R 4 ) b is 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,
is piperidin-4-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than benzoxazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 2-oxo-3,4-dihydro-quinolin-7-yl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
6 . A compound as in claim 4 , wherein
R 1 and R 2 are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl, 1-(methyl-sulfonyl)-piperidin-4,4-diyl, 1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(methoxycarbonyl)azetidin-3,3-diyl, tetrahydro-furan-3,3-diyl, and tetrahydro-pyran-4,4-diyl; m is an integer from 0 to 1; and n is an integer from 0 to 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and piperidin-4-yl;
a is 1;
L 1 is —C(O)—;
R 3 is selected from the group consisting of ethyl, cyclopropyl, 1-hydroxy-cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxymethyl-cyclopropyl, cyclobutyl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl, and oxetan-2-yl;
b is an integer from 0 to 1;
R 4 is selected from the group consisting of 2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro, and 3-methyl;
R 5 is
is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 4-dimethylamino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl, 3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 2-(hydroxymethyl)-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-(cyanomethyl)-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, 2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 8-fluoro-quinolin-7-yl, 4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 6-fluoro-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indaozl-5-yl, 1,4-dimethyl-indazol-5-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzothiazol-2-yl, benzothiazol-5-yl, 6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl, and pyrrolo[2,3-b]pyridin-5-yl;
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than a compound selected from the group consisting of quinolin-7-yl, benzofuran-5-yl and 1-methyl-indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl or indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
7 . A compound as in claim 4 , wherein
R 1 and R 2 are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl; m is an integer from 0 to 1; and n is 0;
is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;
a is 1;
L 1 is —C(O)—;
R 3 is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, tetrahydrfuran-2S-yl, and oxetan-2-yl;
b is an integer from 0 to 1;
R 4 is selected from the group consisting of 2-fluoro, 2-chloro, and 2-methyl;
R 5 is
is selected from the group consisting of 3-hydroxy-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 3-cyanomethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, quinolin-3-yl, quinolin-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 2-cyano-quinolin-6-yl, isoquinolin-6-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothiazol-2-yl, benzthiazol-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, and 2,3-dimethyl-benzothien-5-yl;
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl or indazol-5-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
8 . A compound as in claim 4 , wherein
R 1 and R 2 are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl; m is an integer from 0 to 1; and n is 0;
is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;
a is 1;
L 1 is —C(O)—;
R 3 is selected from the group consisting of cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, and oxetan-2-yl;
b is an integer from 0 to 1;
R 4 is selected from the group consisting of 2-fluoro and 2-methyl;
R 5 is selected from the group consisting of
is selected from the group consisting of naphtha-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, isoquinolin-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl, benzoxazol-2-yl, benzothiazol-2-yl, and 1-methyl-benzimidazol-5-yl;
wherein
is selected from the group consisting of pyridin-4-yl and 1-methyl-pyrazol-4-yl;
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
9 . A compound as in claim 4 , wherein
R 1 and R 2 are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, and tetrahydropyran-4,4-diyl; m is an integer from 0 to 1; and n is 0;
is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;
a is 1;
L 1 is —C(O)—;
R 3 is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl, and oxetan-2-yl;
b is an integer from 0 to 1;
R 4 is selected from the group consisting of 2-fluoro and 2-methyl;
R 5 is selected from the group consisting of
is selected from the group consisting of naphth-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-6-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-6-yl, isoquinolin-6-yl, quinazolin-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-methyl-benzothien-5-yl, benzothiazol-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzimidazol-5-yl, and 1-methyl-benzimidazol-5-yl;
wherein
is selected from the group consisting of 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, and pyridin-4-yl;
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 1-methyl-indazol-5-yl, indazol-5-yl, or 4-(1-isobutyl-pyrazol-5-yl)-phenyl;
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,
is azetidin-3-yl; -(L 1 ) a -R 3 is —C(O)-(1-hydroxy-cyclopropyl);
and (R 4 ) b is 2-methyl; then R 5 is other 1-methyl-indazol-5-yl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
10 . A compound as in claim 4 , wherein
R 1 and R 2 are taken together to form cyclopropyl; m is an integer from 0 to 1; and n is 0;
is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;
a is 1;
L 1 is —C(O)—;
R 3 is cyclopropyl;
is selected from the group consisting of
b is 0;
R 5 is
is selected from the group consisting of indol-5-yl, indol-6-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, benzthiazol-5-yl, benzofuran-5-yl, benzothien-5-yl, and 6-cyano-naphth-2-yl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
11 . A compound as in claim 4 , wherein
R 1 and R 2 are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, tetrahydro-furan-3,3-diyl, tetrahydro-pyran-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl, piperidin-4,4-diyl, 1-(isopropylcarbonyl)-piperidin-4,4-diyl, 1-(2-hydroxyethyl)-piperidin-4,4-diyl, 1-(dimethylamino-methylcarbonyl)-piperidin-4,4-diyl, 1-(methylsulfonyl)piperidin-4,4-diyl, and 1-(cyclopropylcarbonyl)-piperidin-4,4-diyl; m is an integer from 0 to 2; and n is an integer from 0 to 1; provided that when m is 2, then n is 0;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3R-yl, piperidin-3R-yl, and piperidin-4-yl;
a is 1;
L 1 is selected from the group consisting of —C(O)—, —C(O)O— and —SO 2 —;
R 3 is selected from the group consisting of methyl, 1-hydroxyethyl, trifluoromethyl, cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl, tetrahydro-furan-2R-yl, pyrrolidin-1-yl, and thiazol-2-yl;
b is an integer from 0 to 1;
R 4 is selected from the group consisting of 2-fluoro and 2-methyl;
R 5 is
is selected from the group consisting of phenyl, pyridin-3-yl, pyridin-4-yl, and pyrazol-4-yl;
and wherein
is selected from the group consisting of 4-bromo-phenyl, 3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-3-yl, 1-(cyclopropylmethyl)-pyrazol-3-yl, 1-(2-methylpropyl)-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, 1-isobutyl-pyrazol-5-yl, 1-(cyclopropylmethyl)-pyrazol-5-yl, tetrazol-5-yl, 5-methyl-oxazdiazol-2-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, pyrrolidin-1-yl, morpholin-14-yl, imidazol-1-yl, and oxetan-3-yl;
provided that when
is phenyl or pyridin-3-yl, then
is bound to
at the 4-position, relative to the binding position of the
to the
provided further that when
is pyridin-4-yl or pyrazol-4-yl, then
is bound to
at the 3-position, relative to the binding position of the
to the
provided that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)—CF 3 , —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH 3 , and —SO 2 —CH 3 ;
and b=0; then R 5 is other than 4-(1-methyl-pyrazol-4-yl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
b=0 or (R 4 ) b is 2-methyl; then R 5 is other than 2-(piperazin-1-yl)-pyridin-4-yl, or 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0, and
is azetidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);
b=0 or (R 4 ) b is selected from the group consisting of 2-fluoro and 2-methyl; then R 5 is other than 4-(1-isobutyl-pyrazol-5-yl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,
is piperidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 4-(4-methylphenyl)phenyl or 4-(3-chlorophenyl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1, and
is piperidin-4-yl; -(L 1 ) a —R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 4-(1-methyl-pyrazol-4-yl)-phenyl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;
is pyrrolidin-3R-yl; -(L 1 ) a -R 3 is —C(O)-cyclopropyl;
and b=0; then R 5 is other than 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl;
provided further that when R 1 and R 2 are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;
is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, and pyrrolidin-3-yl; -(L 1 ) a -R 3 is selected from the group consisting of —C(O)—CF 3 , —C(O)OCH 3 and —SO 2 —CH 3 ;
and b=0; then R 5 is other than 4-(1-methyl-pyrazol-4-yl)-phenyl; and
a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
12 . A compound as in claim 10 , wherein
R 1 and R 2 are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl; m is an integer from 0 to 1; and n is 0;
is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;
a is 1;
L 1 is —C(O)—;
R 3 is selected from the group consisting of cyclopropyl, 1-hydroxy-cyclopropyl, and 1-methyl-cyclopropyl;
b is an integer from 0 to 1;
R 4 is selected from the group consisting of 2-fluoro and 2-methyl;
R 5 is
and wherein
is selected from the group consisting of pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, and 5-methyl-oxadiazol-2-yl;
wherein
is bound to the
phenyl at the 4-position, relative to the point of attachment of the
phenyl to the
and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
13 . A compound as in claim 1 , selected from the group consisting of
5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-(4-(6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)-2-naphthonitrile; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 5-(4-(benzo[d]thiazol-2-yl)-2-fluorophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; and stereoisomers, tautomers and pharmaceutically acceptable salts thereof.
14 . A compound as in claim 1 , selected from the group consisting of
6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; and stereoisomers, tautomers and pharmaceutically acceptable salts thereof.
15 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 .
16 . A pharmaceutical composition made by mixing a compound of claim 1 and a pharmaceutically acceptable carrier.
17 .- 25 . (canceled)
26 . A compound as in claim 1 for use as a medicament.
27 . A compound as in claim 1 for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme.
28 . A compound as in claim 1 , for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, the disorder selected from the group consisting of cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood and bone.
29 . A compound as in claim 1 , for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, the disorder selected from the group consisting of (a) obesity and related disorders and (b) liver related disorders.
30 . A composition comprising a compound as in claim 1 , for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme.
31 . A composition comprising a compound as in claim 1 , for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme the disorder selected from the group consisting of
(a) cancer selected from the group consisting of breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood, and bone; (b) obesity or a related disorder selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, and appetite or satiety modulation; and (c) a liver related disorders selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD).
32 .- 35 . (canceled)Cited by (0)
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