US 2008/0076783 A1Published application

Cycloalkyl Keto Piperidine Tachykinin Receptor Antagonists

AssigneeMerck & Co., Inc.

InventorsRobert DeVita, Sander Mills, Ronsar Eid, Jonathan Young

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Abstract

The present invention is directed to certain piperidine compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Claims20

Dependent claims

A compound of the formula I:

wherein:
Q is selected from the group consisting of
(1) hydrogen,
(2) C1-6 alkyl, and
(3) C1-6 alkyl-OH;
R1 is selected from the group consisting of:
(1) cyclopentyl,
(2) cyclohexyl, and
(3) cyclopentenone,
which is substituted with R1a, R1b and R1c, wherein R1a, R1b and R1c are independently selected from:
(a) hydrogen,
(b) C1-6 alkyl,
(c) (C1-6 alkyl)-phenyl,
(d) (C1-6 alkyl)-hydroxy,
(e) (C1-6 alkyl)-(C1-4 alkoxy),
(f) hydroxy,
(g) oxo,
(h) C1-6 alkoxy,
(i) phenyl-C1-13 alkoxy,
(j) phenyl,
(k) —CN,
(l) halo,
(m)—NR9R10, wherein R9 and R10 are independently selected from:
(I) hydrogen,
(II) C1-6 alkyl,
(III) phenyl,
(IV) (C1-6 alkyl)-phenyl,
(V) (C1-6 alkyl)-hydroxy, and
(VI) (C1-6 alkyl)-(C1-4 alkoxy),
(n) —NR9—COR10,
(o)—NR9—CO2R10,
(p) heterocycle, wherein heterocycle is selected from the group consisting of:
(A) imidazolyl,
(B) isooxazolyl,
(C) oxadiazolyl,
(D) oxazolyl,
(E) pyrazinyl,
(F) pyrazolyl,
(G) pyridazinyl,
(H) pyridyl,
(I) pyrimidyl,
(J) pyrrolyl,
(K) quinolyl,
(L) tetrazolyl, and
(M) triazolyl,
and where heterocycle is unsubstituted or substituted with C1-6 alkyl or halo;
(q)-cyclopentenone, which is unsubstituted or substituted with C1-6 alkyl,
(r) —NR9-cyclopentenone, where the cyclopentenone is unsubstituted or substituted with C1-6 alkyl,
(s) —CO—NR9R10,
(t) —SO—NR9R10,
(u) —SO2—NR9R10,
(v) —COR9, and
(w) —CO2R9;
R6, R7 and R8 are independently selected from the group consisting of:
(1) hydrogen,
(2) C1-6alkoxy,
(3) halo,
(4) C1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:
(a) hydroxy,
(b) oxo,
(c) C1-6 alkoxy,
(d) phenyl-C1-3 alkoxy,
(e) phenyl,
(f) —CN,
(g) halo,
(h) —NR9R10,
(i) —NR9—COR10,
(j) —NR9—CO2R10,
(k) —CO—NR9R10,
(l)—COR9,
(m)—CO2R9,
(5) hydroxy,
(6) —CN,
(7) —CF3,
(8) —NO2,
(9) —SR14, wherein R14 is hydrogen or C1-6alkyl,
(10) —SOR14,
(11) —SO2R14,
(12) —NR9—COR10,
(13) —CO—NR9—COR10,
(14) —NR9R10,
(15) —NR9—CO2R10,
(16) —COR9, and
(17) —CO2R9;
R11, R12 and R13 are independently selected from:
(1) hydrogen,
(2) C1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:
(a) hydroxy,
(b) oxo,
(c) C1-6 alkoxy,
(d) phenyl-C1-3 alkoxy,
(e) phenyl,
(f) —CN,
(g) halo,
(h) —NR9R10,
(i) —NR9—COR10,
(j)—NR9—CO2R10,
(k) —CO—NR9R10,
(l) —COR9,
(m)—CO2R9;
(3) halo,
(4) —CN,
(5) —CF3,
(6) —NO2,
(7) hydroxy,
(8) C1-6alkoxy,
(9) —COR9, and
(10) —CO2R9;
and pharmaceutically acceptable salts and individual diasteromers thereof.

106 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/667,284Filed 18 Nov 2005
Priority: 22 Nov 2004
Published: 27 Mar 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 401/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics

Family

Application60/630,138Us provisional application · filed 22 Nov 2004
US 2008/0076783 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of the formula I:

wherein:
Q is selected from the group consisting of
(1) hydrogen,
(2) C1-6 alkyl, and
(3) C1-6 alkyl-OH;
R1 is selected from the group consisting of:
(1) cyclopentyl,
(2) cyclohexyl, and
(3) cyclopentenone,
which is substituted with R1a, R1b and R1c, wherein R1a, R1b and R1c are independently selected from:
(a) hydrogen,
(b) C1-6 alkyl,
(c) (C1-6 alkyl)-phenyl,
(d) (C1-6 alkyl)-hydroxy,
(e) (C1-6 alkyl)-(C1-4 alkoxy),
(f) hydroxy,
(g) oxo,
(h) C1-6 alkoxy,
(i) phenyl-C1-13 alkoxy,
(j) phenyl,
(k) —CN,
(l) halo,
(m)—NR9R10, wherein R9 and R10 are independently selected from:
(I) hydrogen,
(II) C1-6 alkyl,
(III) phenyl,
(IV) (C1-6 alkyl)-phenyl,
(V) (C1-6 alkyl)-hydroxy, and
(VI) (C1-6 alkyl)-(C1-4 alkoxy),
(n) —NR9—COR10,
(o)—NR9—CO2R10,
(p) heterocycle, wherein heterocycle is selected from the group consisting of:
(A) imidazolyl,
(B) isooxazolyl,
(C) oxadiazolyl,
(D) oxazolyl,
(E) pyrazinyl,
(F) pyrazolyl,
(G) pyridazinyl,
(H) pyridyl,
(I) pyrimidyl,
(J) pyrrolyl,
(K) quinolyl,
(L) tetrazolyl, and
(M) triazolyl,
and where heterocycle is unsubstituted or substituted with C1-6 alkyl or halo;
(q)-cyclopentenone, which is unsubstituted or substituted with C1-6 alkyl,
(r) —NR9-cyclopentenone, where the cyclopentenone is unsubstituted or substituted with C1-6 alkyl,
(s) —CO—NR9R10,
(t) —SO—NR9R10,
(u) —SO2—NR9R10,
(v) —COR9, and
(w) —CO2R9;
R6, R7 and R8 are independently selected from the group consisting of:
(1) hydrogen,
(2) C1-6alkoxy,
(3) halo,
(4) C1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:
(a) hydroxy,
(b) oxo,
(c) C1-6 alkoxy,
(d) phenyl-C1-3 alkoxy,
(e) phenyl,
(f) —CN,
(g) halo,
(h) —NR9R10,
(i) —NR9—COR10,
(j) —NR9—CO2R10,
(k) —CO—NR9R10,
(l)—COR9,
(m)—CO2R9,
(5) hydroxy,
(6) —CN,
(7) —CF3,
(8) —NO2,
(9) —SR14, wherein R14 is hydrogen or C1-6alkyl,
(10) —SOR14,
(11) —SO2R14,
(12) —NR9—COR10,
(13) —CO—NR9—COR10,
(14) —NR9R10,
(15) —NR9—CO2R10,
(16) —COR9, and
(17) —CO2R9;
R11, R12 and R13 are independently selected from:
(1) hydrogen,
(2) C1-6 alkyl, unsubstituted or substituted with one or more of the substituents selected from:
(a) hydroxy,
(b) oxo,
(c) C1-6 alkoxy,
(d) phenyl-C1-3 alkoxy,
(e) phenyl,
(f) —CN,
(g) halo,
(h) —NR9R10,
(i) —NR9—COR10,
(j)—NR9—CO2R10,
(k) —CO—NR9R10,
(l) —COR9,
(m)—CO2R9;
(3) halo,
(4) —CN,
(5) —CF3,
(6) —NO2,
(7) hydroxy,
(8) C1-6alkoxy,
(9) —COR9, and
(10) —CO2R9;
and pharmaceutically acceptable salts and individual diasteromers thereof.

106 more elements

Facts

Application

11/667,284Filed 18 Nov 2005

Priority

22 Nov 2004

Published

27 Mar 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification30 codes

C07D 401/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics