US2004082612A1PendingUtilityA1
Benzyl substituted (piperidin-4-yl)aminobenzamido derivatives
Individually held — no corporate assignee on recordPriority: Oct 15, 2002Filed: Oct 14, 2003Published: Apr 29, 2004
Est. expiryOct 15, 2022(expired)· nominal 20-yr term from priority
C07D 211/58C07D 211/56A61P 29/00C07D 401/12
42
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention is directed to N-benzyl substituted (piperidin-4-yl)aminobenzamido derivatives which are delta-opioid receptor modulators.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula (I):
wherein:
Ar is selected from the group consisting of aryl and heteroaryl;
m is an integer from 0 to 2, n is an integer from 0 to 2, with the proviso that m and n are not both simultaneously 0;
R 1 is selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, aryl, aryl(C 1-8 )alkyl, heteroaryl(C 1-8 )alkyl, amino(C 1-8 )alkyl, C 1-8 alkyl-NH—(C 1-8 )alkyl, (C 1-8 alkyl) 2 —N—(C 1-8 )alkyl, hydroxy(C 1-8 )alkyl and C 1-8 alkoxy(C 1-8 )alkyl;
R 2 and R 3 are optionally present and independently selected from C 1-8 alkyl;
R 4 is one to three substituents independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, aryl(C 1-8 )alkyl, C 1-8 alkoxy, aryloxy, aryl(C 1-8 )alkyloxy, C 1-8 alkylthio, trifluoro(C 1-8 )alkyl, trifluoro(C 1-8 )alkoxy, amino, —NH(C 1-8 )alkyl, —N[(C 1-8 )alkyl] 2 , —NH(aryl), —N(aryl) 2 , —NH(C 1-8 )alkylaryl, —N[(C 1-8 )alkylaryl] 2 , —CO 2 H, —CO 2 (C 1-8 )alkyl, —CO 2 (aryl), —C(O)NH 2 , —C(O)NH(C 1-8 )alkyl, —C(O)N[(C 1-8 )alkyl] 2 , —NHC(O)(C 1-8 )alkyl, —SO 2 H, —SO 2 (C 1-8 )alkyl, —S(O 2 )NH 2 , —S(O 2 )NH(C 1-8 )alkyl, —S(O 2 )N[(C 1-8 )alkyl] 2 , —C(O)(C 1-8 )alkyl, —C(O)aryl, —C(O)(C 1-8 )alkylaryl, aryl, heteroaryl, heterocyclyl, halogen, hydroxy, cyano, and nitro;
is selected from the group consisting of O and S;
Z is N(R 5 )(R 6 ) or is a 5- or 6-membered saturated, monocyclic, heterocyclic ring, wherein said heterocyclic ring contains one nitrogen member which is the point of attachment, optionally contains one additional heteroatom member of oxygen, sulfur or nitrogen and optionally contains a double bond between two ring members;
R 5 and R 6 are independently selected from the group consisting of hydrogen, C 1-8 alkyl, hydroxy(C 1-8 )alkyl, C 2-8 alkenyl, C 3-8 cycloalkyl, aryl and aryl(C 1-8 )alkyl, wherein said cycloalkyl, aryl and the aryl portion of aryl(C 1-8 )alkyl are optionally substituted with one to three substituents independently selected from the group consisting of C 1-8 alkyl, C 2-8 alkenyl, C 1-8 alkoxy, trifluoro(C 1-8 )alkyl, trifluoro(C 1-8 )alkoxy, C 3-8 cycloalkyl and halogen; and,
the moiety —C(X)Z is attached on the phenyl at the 3 or 4 position;
and pharmaceutically acceptable enantiomers, diastereomers and salts thereof.
2 . The compound of claim 1 wherein Ar is phenyl, naphthyl, furyl, thienyl, oxazolyl, thiazolyl, imidazolyl, isozazolyl, isothiazolyl, indolyl, indazolyl, benzo[b]thienyl, quinolinyl, isoquinolinyl, quinazolinyl, pyrrolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl.
3 . The compound of claim 1 wherein Ar is phenyl or pyridinyl.
4 . The compound of claim 1 wherein m is an integer from 0 to 1, n is an integer from 0 to 1, with the proviso that m and n are not both simultaneously 0.
5 . The compound of claim 1 R 1 is selected from the group consisting of hydrogen, C 1-4 alkyl, C 2-4 alkenyl, aryl, aryl(C 1-4 )alkyl, heteroaryl(C 1-4 )alkyl, NH 2 (C 1-4 )alkyl, C 1-4 alkyl-NH—(C 1-4 )alkyl, (C 1-4 alkyl) 2 —N—(C 1-4 )alkyl, hydroxy(C 1-4 )alkyl and C 1-4 alkoxy(C 1-4 )alkyl.
6 . The compound of claim 1 wherein R 1 is selected from the group consisting of hydrogen, C 1-4 alkyl and C 2-4 alkenyl.
7 . The compound of claim 1 wherein R 1 is selected from the group consisting of hydrogen, n-propyl and allyl.
8 . The compound of claim 1 wherein R 2 and R 3 are optionally present and independently selected from C 1-4 alkyl.
9 . The compound of claim 1 wherein R 2 and R 3 are not present.
10 . The compound of claim 1 wherein R 4 is one to three substituents.
11 . The compound of claim 1 wherein R 4 is independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 1-8 alkoxy, trifluoro(C 1-8 )alkyl, trifluoro(C 1-8 )alkoxy, cyano, halogen, hydroxy and nitro.
12 . The compound of claim 1 wherein R 4 is independently selected from the group consisting of hydrogen, C 1-8 alkoxy, trifluoro(C 1-8 )alkyl, hydroxy and halogen.
13 . The compound of claim 1 wherein R 4 is independently selected from the group consisting of hydrogen, methoxy, trifluoromethyl, hydroxy, fluoro and chloro.
14 . The compound of claim 1 wherein X is 0.
15 . The compound of claim 1 wherein Z is N(R 5 )(R 6 ).
16 . The compound of claim 1 wherein R 5 and R 6 are independently selected from the group consisting of hydrogen, C 1-4 alkyl, hydroxy(C 1-4 )alkyl, C 2-4 alkenyl, C 3-8 cycloalkyl, aryl and aryl(C 1-4 )alkyl, wherein said cycloalkyl, aryl and the aryl portion of aryl(C 1-8 )alkyl are optionally substituted with one to three substituents independently selected from the group consisting of C 1-4 alkyl, C 2-4 alkenyl, C 1-4 alkoxy, C 3-8 cycloalkyl, halogen, trifluoro(C 1-4 )alkyl and trifluoro(C 1-4 )alkoxy.
17 . The compound of claim 1 wherein R 5 and R 6 are independently selected from the group consisting of hydrogen and C 1-4 alkyl.
18 . The compound of claim 1 wherein R 5 and R 6 independently selected from the group consisting of hydrogen, methyl and ethyl.
19 . The compound of claim 1 wherein the compound of Formula (I) is selected from Formula (Ia):
wherein
Ar is selected from the group consisting of aryl and heteroaryl;
R 1 is selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, aryl, aryl(C 1-8 )alkyl, heteroaryl(C 1-8 )alkyl, amino(C 1-8 )alkyl, C 1-8 alkyl-NH—(C 1-8 )alkyl, (C 1-8 alkyl) 2 —N—(C 1-8 )alkyl, hydroxy(C 1-8 )alkyl and C 1-8 alkoxy(C 1-8 )alkyl;
R 4 is one to three substituents independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, aryl(C 1-8 )alkyl, C 1-8 alkoxy, aryloxy, aryl(C 1-8 )alkyloxy, C 1-8 alkylthio, trifluoro(C 1-8 )alkyl, trifluoro(C 1-8 )alkoxy, amino, —NH(C 1-8 )alkyl, —N[(C 1-8 )alkyl] 2 , —NH(aryl), —N(aryl) 2 , —NH(C 1-8 )alkylaryl, —N[(C 1-8 )alkylaryl] 2 , —CO 2 H, —CO 2 (C 1-8 )alkyl, —CO 2 (aryl), —C(O)NH 2 , —C(O)NH(C 1-8 )alkyl, —C(O)N[(C 1-8 )alkyl] 2 , —NHC(O)(C 1-8 )alkyl, —SO 2 H, —SO 2 (C 1-8 )alkyl, —S(O 2 )NH 2 , —S(O 2 )NH(C 1-8 )alkyl, —S(O 2 )N[(C 1-8 )alkyl] 2 , —C(O)(C 1-8 )alkyl, —C(O)aryl, —C(O)(C 1-8 )alkylaryl, aryl, heteroaryl, heterocyclyl, halogen, hydroxy, cyano, and nitro;
and pharmaceutically acceptable enantiomers, diastereomers and salts thereof.
20 . The compound of claim 1 wherein the compound of Formula (I) is selected from Formula (Ia):
Wherein Ar, R 1 and R 4 are dependently selected from:
R 1
Ar
R 4
n-Pr
phenyl
3-methoxy
n-Pr
phenyl
3-hydroxy
n-Pr
phenyl
3-chloro
n-Pr
phenyl
2-methoxy
n-Pr
phenyl
2-hydroxy
n-Pr
phenyl
3-fluoro
n-Pr
phenyl
H
H
phenyl
H
allyl
phenyl
H
i-Pr
phenyl
H
N, N-dimethyl
phenyl
H
aminopropyl
n-Pr
phenyl
4-methoxy
n-Pr
3-pyridinyl
H
Me
phenyl
H
n-Pr
phenyl
3-trifluoromethyl
n-Pr
phenyl
4-fluoro
and pharmaceutically acceptable salts thereof.
21 . The compound of claim 1 wherein the compound of Formula (I) is selected from Formula (Ib):
wherein
Ar is selected from the group consisting of aryl and heteroaryl;
R 4 is one to three substituents independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, aryl(C 1-8 )alkyl, C 1-8 alkoxy, aryloxy, aryl(C 1-8 )alkyloxy, C 1-8 alkylthio, trifluoro(C 1-8 )alkyl, trifluoro(C 1-8 )alkoxy, amino, —NH(C 1-8 )alkyl, —N[(C 1-8 )alkyl] 2 , —NH(aryl), —N(aryl) 2 , —NH(C 1-8 )alkylaryl, —N[(C 1-8 )alkylaryl] 2 , —CO 2 H, —CO 2 (C 1-8 )alkyl, —CO 2 (aryl), —C(O)NH 2 , —C(O)NH(C 1-8 )alkyl, —C(O)N[(C 1-8 )alkyl] 2 , —NHC(O)(C 1-8 )alkyl, —SO 2 H, —SO 2 (C 1-8 )alkyl, —S(O 2 )NH 2 , —S(O 2 )NH(C 1-8 )alkyl, —S(O 2 )N[(C 1-8 )alkyl] 2 , —C(O)(C 1-8 )alkyl, —C(O)aryl, —C(O)(C 1-8 )alkylaryl, aryl, heteroaryl, heterocyclyl, halogen, hydroxy, cyano, and nitro;
the moiety —C(X)Z is attached on the phenyl at the 3 or 4 position;
and pharmaceutically acceptable enantiomers, diastereomers and salts thereof.
22 . The compound of claim 1 wherein the compound of Formula (I) is selected from Formula (Ib):
Wherein Ar, R 4 and the position for —C(O)(NEt 2 ) is selected from:
Amide
Ar
R 4
Substitution
phenyl
3-methoxy
4
phenyl
3-methoxy
3
phenyl
3-hydroxy
3
phenyl
H
3
phenyl
3-fluoro
3
23 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
24 . A method for preparing a pharmaceutical composition comprising mixing a compound of claim 1 and a pharmaceutically acceptable carrier.
25 . A method for treating a disorder modulated by the δ-opioid receptor in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of claim 1 .
26 . The method of claim 25 wherein the therapeutically effective amount of the compound of claim 1 is from about 0.001 mg/day to about 12,000 mg/day.
27 . The method of claim 25 wherein the disorder is pain modulated by a therapeutically effective amount of a compound of claim 1 .
28 . The method of claim 25 wherein the disorder is selected from the group consisting of immune disorders, inflammation, neurological conditions, psychiatric conditions, drug abuse, alcohol abuse, gastritis, diarrhea, cardiovascular disorders and respiratory disorders modulated by a therapeutically effective amount of a compound of claim 1 .
29 . The method of claim 25 further comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 23 .
30 . The method of claim 25 wherein the therapeutically effective amount of the pharmaceutical composition of claim 23 is from about 0.001 mg/day to about 12,000 mg/day.Join the waitlist — get patent alerts
Track US2004082612A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.