US2010234591A1PendingUtilityA1
Biaryl heterocyclic compounds and methods of making and using the same
Est. expiryJun 3, 2023(expired)· nominal 20-yr term from priority
Inventors:Jiacheng ZhouAshoke BhattacharjeeShili ChenYi ChenJay J. FarmerJoel A. GoldbergRoger HanselmannRongliang LouAlia OrbinAdegboyega K. OyelereJoseph M. SalvinoDane M. SpringerJennifer TranDeping WangYusheng Wu
A61P 9/00A61P 41/00A61P 31/12A61P 33/00A61P 31/00A61P 29/00A61P 31/04A61P 35/00A61P 31/10A61P 31/02A61P 11/00A61P 13/02A61P 1/00A61P 19/02A61P 17/00A61P 1/04A61P 19/08C07D 263/20C07D 417/10C07D 473/34C07D 487/04C07D 471/04C07D 473/00C07D 417/14C07D 417/12C07D 263/24C07D 453/02C07D 263/32C07D 413/14C07D 263/26C07D 413/10C07D 413/12
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Claims
Abstract
The present invention relates generally to the field of anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents. More particularly, the invention relates to a family of compounds having both a biaryl moiety and at least one heterocylic moiety that are useful as such agents.
Claims
exact text as granted — not AI-modified1 . A compound having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein:
A is selected from the group consisting of:
phenyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl;
B is selected from the group consisting of:
phenyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl;
Het-CH 2 —R 3 is selected from the group consisting of:
M is selected from the group consisting of:
a) saturated, unsaturated, or aromatic C 3-14 carbocycle, and b) saturated, unsaturated, or aromatic 3-14 membered heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein a) or b) optionally is substituted with one or more R 5 groups;
M-L is selected from the group consisting of:
a) M-X, b) M-L 1 , c) M-L 1 -X, d) M-X-L 2 , e) M-L 1 -X-L 2 , f) M-X-L 1 -X-L 2 , g) M-L 1 -X-L 2 -X, h) M-X—X—, i) M-L 1 -X—X—, j) M-X—X-L 2 , and k) M-L 1 -X—X-L 2 , wherein
X, at each occurrence, independently is selected from the group consisting of:
a) —O—, b) —NR 4 —, c) —N(O)—, d) —N(OR 4 )—, e) —S(O) p —, f) —SO 2 NR 4 —, g) —NR 4 SO 2 —, h) —NR 4 —N═, i) ═N—NR 4 —, j) k) ═N—O—, l) —N═, m) αN—, n) —NR 4 —NR 4 —, o) —NR 4 C(O)O—, p) —OC(O)NR 4 —, q) —NR 4 C(O)NR 4 — r) —NR 4 C(NR 4 )NR 4 —, and s)
L 1 is selected from the group consisting of:
a) C 1-6 alkyl, b) C 2-6 alkenyl, and c) C 2-6 alkynyl,
wherein any of a)-c) optionally is substituted with one or more R 5 groups; and
L 2 is selected from the group consisting of:
a) C 1-6 alkyl, b) C 2 - 6 alkenyl, and c) C 2-6 alkynyl,
wherein any of a)-c) optionally is substituted with one or more R 5 groups;
R 1 , at each occurrence, independently is selected from the group consisting of:
a) F, b) Cl, c) Br, d) I, e) —CF 3 , f) —OR 4 ,g) —CN, h) —NO 2 , i) —NR 4 R 4 , j) —C(O)R 4 , k) —C(O)OR 4 , l) —OC(O)R 4 , m) —C(O)NR 4 R 4 , n) —NR 4 C(O)R 4 , a) —OC(O)NR 4 R 4 , p) —NR 4 C(O)OR 4 , q) —NR 4 C(O)NR 4 R 4 , r) —C(S)R 4 , s) —C(S)OR 4 , t) —OC(S)R 4 , u) —C(S)NR 4 R 4 , v) —NR 4 C(S)R 4 , w) —OC(S)NR 4 R 4 , x) —NR 4 C(S)OR 4 , y) —NR 4 C(S)NR 4 R 4 , z) —NR 4 C(NR 4 )NR 4 R 4 , aa) —S(O) p R 4 , bb) —SO 2 NR 4 R 4 , and cc) R 4 ;
R 2 , at each occurrence, independently is selected from the group consisting of
a) F, b) Cl, c) Br, d) I, e) —CF 3 , f) —OR 4 , g) —CN, h) —NO 2 , i) —NR 4 R 4 , j) —C(O)R 4 , k) —C(O)OR 4 , l) —OC(O)R 4 , m) —C(O)NR 4 R 4 , n) —NR 4 C(O)R 4 , o) —C(O)NR 4 R 4 , p) —NR 4 C(O)OR 4 , q) —NR 4 C(O)NR 4 R 4 , r) —C(S)R 4 , s) —C(S)OR 4 , t) —OC(S)R 4 , u) —C(S)NR 4 R 4 , v) —NR 4 C(S)R 4 , w) —OC(S)NR 4 R 4 , x) —NR 4 C(S)OR 4 , y) —NR 4 C(S)NR 4 R 4 , z) —NR 4 C(NR 4 )NR 4 R 4 , aa) —S(O) p R 4 , bb) —SO 2 NR 4 R 4 , and cc) R 4 ;
R 3 is selected from the group consisting of:
—OR 4 , b) —NR 4 R 4 , c) —C(O)R 4 , d) —C(O)OR 4 , e) —OC(O)R 4 , f) —C(O)NR 4 R 4 , g) —NR 4 C(O)R 4 , h) —OC(O)NR 4 R 4 , i) —NR 4 C(O)OR 4 , j) —NR 4 C(O)NR 4 R 4 , k) —C(S)R 4 , l) —C(S)OR 4 , m) —OC(S)R 4 , n) —C(S)NR 4 R 4 , o) —NR 4 C(S)R 4 , p) —OC(S)NR 4 R 4 , q) —NR 4 C(S)OR 4 , r) —NR 4 C(S)OR 4 , r) —NR 4 C(S)NR 4 R 4 , s) —NR 4 C(NR 4 )NR 4 R 4 , t) —S(O) p R 4 , u) —SO 2 NR 4 R 4 , and v) R 4 ;
R 4 , at each occurrence, independently is selected from the group consisting of:
a) H, b) C 1-6 alkyl, c) C 2-6 alkenyl, d) C 2-6 alkynyl, e) C 3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, g) —C(O)—C 1-6 alkyl, h) —C(O)—C 2-6 alkenyl, i) —C(O)—C 2-6 alkynyl, j) —C(O)—C 3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, l) —C(O)O—C 1-6 alkyl, m) —C(O)O—C 2-6 alkenyl, n) —C(O)O—C 2-6 alkynyl, o) —C(O)—O—C 3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein any of b)-p) optionally is substituted with one or more R 5 groups;
R 5 , at each occurrence, is independently selected from the group consisting of:
a) F, b) Cl, a) Br, d) I, e) ═O, f) ═S, g) ═NR 6 , h) ═NOR 6 , i) ═N—NR 6 R 6 , j) —CF 3 , k) —OR 6 , l) —CN, m) —NO 2 , n) —NR 6 R 6 , o) —C(O)R 6 , p) —C(O)OR 6 , q) —OC(O)R 6 , r) —C(O)NR 6 R 6 , s) —NR 6 C(O)R 6 , t) —OC(O)NR 6 R 6 , u) —NR 6 C(O)OR 6 , v) —NR 6 C(O)NR 6 R 6 , w) —C(S)R 6 , x) —C(S)OR 6 , y) —OC(S)R 6 , z) —C(S)NR 6 R 6 , aa) —NR 6 C(S)R 6 , bb) —OC(S)NR 6 R 6 , cc) —NR 6 C(S)OR 6 , dd) —NR 6 C(S)NR 6 R 6 , ee) —NR 6 C(NR 6 )NR 6 R 6 , ff) —S(O) p R 6 , gg) —SO 2 NR 6 R 6 , and hh) R 6 ;
R 6 , at each occurrence, independently is selected from the group consisting of:
a) H, b) C 1-6 alkyl, c) C 2-6 alkenyl, d) C 2-6 alkynyl, e) C 3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, g) —C(O)—C 1-6 alkyl, h) —C(O)—C 2-6 alkenyl, i) —C(O)—C 2-6 alkynyl, j) —C(O)—C 3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, l) —C(O)O—C 1-6 alkyl, m) —C(O)O—C 2-6 alkenyl, n) —C(O)O—C 2-6 alkynyl, o) —C(O)O—C 3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein any of b) p) optionally is substituted with one or more R 7 groups;
R 7 , at each occurrence, independently is selected from the group consisting of:
a) F, b) Cl, c) Br, d) I, e) ═O, f) ═S, g) ═NR 9 , h) ═NOR 8 , i) ═N—NR 8 R 8 , j) —CF 3 , k) —OR 8 , l) —CN, m) —NO 2 , n) a) —C(O)R 8 , p) —C(O)OR 8 , q) —OC(O)R 8 , r) —C(O)NR 8 R 8 , s) —NR 8 C(O)R 8 , t) —OC(O)NR 8 R 8 , u) —NR 8 C(O)OR 8 , v) —NR 8 C(O)NR 8 R 8 , w) —C(S)R 8 , x) —C(S)OR 8 , y) —OC(S)R 8 , z) —C(S)NR 8 R 8 , aa) —NR 8 C(S)R 8 , bb) —OC(S)NR 8 R 8 , cc) —NR 8 C(S)OR 8 , dd) —NR 8 C(S)NR 8 R 8 , ee) —NR 8 C(NR 8 )NR 8 R 9 , ff) —S(O) p R 8 , gg) —SO 2 NR 8 R 8 , hh) C 1-6 alkyl, ii) C 2-6 alkenyl, jj) C 2-6 alkynyl, kk) C 3-14 saturated, unsaturated, or aromatic carbocycle, and ll) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein any of hh)-ll) optionally is substituted with one or more moieties selected from the group consisting of R 8 , F, Cl, Br, I, 'CF 3 , —OR 8 , —SR 8 , —CN, —NO 2 , —NR 8 R 8 , —C(O)R 8 , —C(O)OR 8 , —OC(O)R 8 , —C(O)NR 8 R 8 , —NR 8 C(O)R 8 , —OC(O)NR 8 R 8 , —NR 8 C(O)OR 8 , —NR 8 C(O)NR 8 R 8 , —C(S)R 8 , —C(S)OR 8 , —OC(S)R 8 , —C(S)NR 8 R 8 , —NR 8 C(S)R 8 , —OC(S)NR 8 R 8 , —NR 8 C(S)OR 8 , —NR 8 C(S)NR 8 R 8 , —NR 8 C(NR 8 )NR 8 R 8 , —SO 2 NR 8 R 8 , and —S(O) p R 8 ;
R 8 , at each occurrence, independently is selected from the group consisting of:
a) H, b) C 1-6 alkyl, c) C 2-6 alkenyl, d) C 2-6 alkynyl, e) C 3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, g) —C(O)—C 1-6 alkyl, h) —C(O)—C 2-6 alkenyl, i) —C(O)—C 2-6 alkynyl, j) —C(O)—C 3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, l) —C(O)O—C 1-6 alkyl, m) —C(O)O—C 2-5 alkenyl, n) —C(O)O—C 2-6 alkynyl, o) —C(O)O—C 3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein any of b)-p) optionally is substituted with one or more moieties selected from the group consisting of F, Cl, Br, I, —CF 3 , —OH, —OCH 3 , —SH, —SCH 3 , —CN, —NO 2 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —C(O)CH 3 , —C(O)OCH 3 , —C(O)NH 2 , —NHC(O)CH 3 , —SO 2 NH 2 , —SO 2 NHCH 3 , —SO 2 N(CH 3 ) 2 , and —S(O) p CH 3 ;
m is 0, 1, 2, 3, or 4;
n is 0, 1, 2, 3, or 4; and
p, at each occurrence, independently is 0, 1, or 2,
and wherein the compound does not have the formula corresponding to any of the structures listed in Table 1.
2 . The compound according to claim 1 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein A, B, L, M, R 1 , R 2 , R 3 , m, and n are defined as described in claim 1 .
3 . The compound according to claim 2 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein A, B, L, M, R 1 , R 2 , R 3 , m, and n are defined as described in claim 1 .
4 . The compound according to claim 1 , wherein
A is selected from the group consisting of phenyl and pyridyl; B is selected from the group consisting of phenyl and pyridyl; m is 0, 1, or 2; and n is 0, 1, or 2.
5 . The compound according to claim 1 , wherein A-B is:
wherein A, R 2 , and n are defined as described in claim 1 .
6 . The compound according to claim 5 , wherein A-B is:
wherein A is defined as described in claim 1 ,
7 . The compound according to claim 5 , wherein A-B is:
wherein A is defined as described in claim 1 .
8 . The compound according to claim 1 , wherein A-B is:
wherein B is defined as described in claim 1 .
9 . The compound according to claim 1 , wherein A-B is:
wherein B is defined as described in claim 1 .
10 . The compound according to claim 1 , wherein R 3 is —NHC(O)R 4 .
11 . The compound according to claim 10 , wherein R 4 is —CH 3 .
12 . The compound according to claim 1 , wherein R 3 is:
13 . The compound according to claim 1 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein A, B, L, M, R 1 , R 2 , m, and n are defined as described in claim 1 .
14 . The compound according to claim 1 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein A, L, M, R 1 , R 3 , and m are defined as described in claim 1 .
15 . The compound according to claim 1 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein A, L, M, R 1 , and m are defined as described in claim 1 .
16 . The compound according to claim 1 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein L, M, and R 3 are defined as described in claim 1 .
17 . The compound according to claim 1 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein L, M, and R 3 are defined as described in claim 1 .
18 . The compound according to claim 17 , wherein R 3 is —NHC(O)CH 3 .
19 . The compound according to claim 1 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein A, L, M, R 1 , R 3 , and m are defined as described in claim 1 .
20 . The compound according to claim 1 , having the formula:
or a pharmaceutically acceptable salt, ester or prodrug thereof,
wherein A, L, M, R 1 , and m are defined as described in claim 1 .Cited by (0)
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