# US 2008/0188481 A1 · Indole, azaindole and related heterocyclic 4-alkenyl piperidine amides

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- Number: US 2008/0188481 A1
- Document ID: US20080188481A1
- Status: Published application
- Kind: A1
- Application number: 12/015,767
- Filed: 2008-01-17
- Published: 2008-08-07
- Earliest claimed: 2002-05-28
- Assignees: Bristol-Myers Squibb Company
- Inventors: Tao Wang; John F. Kadow; Nicholas A. Meanwell; Kap-Sun Yeung; Zhongxing Zhang; Zhiwei Yin; Zhilei Qiu; Daniel H. Deon; Clint A. James; Edward H. Ruediger; Carol Bachand
- Web page: https://patentgrep.com/patent/US20080188481A1

## CPC

- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61P 31/18: for HIV
- C07D 413/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with new piperidine 4-alkenyl derivatives that possess unique antiviral activity. More particularly, the present invention relates to compounds useful for the treatment of HIV and AIDS. The compounds of the invention for the general Formula I: wherein: Z is Q is selected from the group consisting of: —W— is

## Claims

### Claim 1

A method for treating mammals infected with HIV, comprising administering to said mammal an antiviral effective amount of a compound of Formula I, including pharmaceutically acceptable salts thereof,
wherein:
Z is
Q is selected from the group consisting of:
—W— is
R1, R2, R3, R4 and R5, are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, COOR8, XR9, and B;
R6 is O or does not exist;
R7 is (CH2)nR10;
n is 0-6;
R10 is selected from the group consisting of H, (C1-6)alkyl, —C(O)—(C1-6)alkyl, C(O)-phenyl and CONR11R12;
R11 and R12 are each independently H, (C1-6)alkyl or phenyl;
-- represents a carbon-carbon bond or does not exist;
D is selected from the group consisting of hydrogen, (C1-6)alkyl, (C1-6)alkynyl, (C3-6) cycloalkyl, halogen, cyano, —CONR32R33, —SO2R32, COR32, COOR8, tetrahydrofuryl, pyrrolidinyl, phenyl and heteroaryl; wherein said (C1-6)alkyl, (C1-6)alkynyl, phenyl and heteroaryl are each independently optionally substituted with one to three same or different members selected from the group G; heteroaryl is selected from the group consisting of furanyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrazolyl, tetrazolyl, triazolyl, pyridinyl, pyrazinyl, pyridazinyl, and pyrimidinyl;
A is selected from the group consisting of phenyl and heteroaryl; wherein said phenyl and heteroaryl are each independently optionally substituted with one to three same or different members selected from the group K; and heteroaryl is selected from the group consisting of pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, thienyl, benzothienyl, thiazolyl, isothiazolyl, oxazolyl, benzooxazolyl, isoxazolyl, imidazolyl, benzoimidazolyl, 1H-imidazo[4,5-b]pyridin-2-yl, 1H-imidazo[4,5-c]pyridin-2-yl, oxadiazolyl, thiadiazolyl, pyrazolyl, tetrazolyl, tetrazinyl, triazinyl and triazolyl; with the proviso that when m is 1 and A is benzoimidazolyl, 1H-imidazo[4,5-b]pyridin-2-yl or 1H-imidazo[4,5-c]pyridin-2-yl, D is not —H; R15, R16, R17, R18, R19, R20, R21, R22 are each independently selected from the group consisting of H and (C1-6)alkyl; wherein (C1-6)alkyl is optionally substituted with one to three same or different halogen, amino, OH, CN or NO2;
B is selected from the group consisting of (C1-6)alkyl, (C3-6)cycloalkyl, C(O)NR23R24, phenyl and heteroaryl; wherein said (C1-6)alkyl, phenyl and heteroaryl are independently optionally substituted with one to three same or different halogens or from one to three same or different substituents selected from F; heteroaryl is selected from the group consisting of pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, thienyl, benzothienyl, thiazolyl, isothiazolyl, oxazolyl, benzooxazolyl, isoxazolyl, imidazolyl, benzoimidazolyl, 1H-imidazo[4,5-b]pyridin-2-yl, 1H-imidazo[4,5-c]pyridin-2-yl, oxadiazolyl, thiadiazolyl, pyrazolyl, tetrazolyl, tetrazinyl, triazinyl and triazolyl;
F is selected from the group consisting of (C1-6)alkyl, (C3-6)cycloalkyl cyano, phenyl, heteroaryl, heteroalicyclic, hydroxy, (C1-6)alkoxy, halogen, benzyl, —NR25C(O)—(C1-6)alkyl, —NR26R27, morpholino, nitro, —S(C1-6)alkyl, —SPh, NR25S(O)2—R26, piperazinyl, N-Me piperazinyl, C(O)H, (CH2)nCOOR28 and —CONR29R30; wherein said (C1-6)alkyl, heteroaryl, or phenyl is optionally substituted with one to three same or different halogens or one to three methyl groups; heteroaryl is selected from the group consisting of furanyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrazolyl, tetrazolyl, triazolyl, pyridinyl, pyrazinyl, pyridazinyl, and pyrimidinyl; heteroalicyclic is selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, N-methyl piperazine, piperidine, tetrahydrofuran, tetrahydropyran, azepine and morpholine;
G is selected from the group consisting of (C1-6)alkyl, (C3-6)cycloalkyl cyano, trimethylsilyl, phenyl, heteroaryl, heteroalicyclic, hydroxy, (C1-6)alkoxy, halogen, benzyl, —NR25C(O)—(C1-6)alkyl, —NR26R27, —C(O)NR26R27, morpholino, nitro, —S(C1-6)alkyl, —SPh, NR25S(O)2—R26, piperazinyl, N-Me piperazinyl, (CH2)nCOOR28 and —CONR29R30; wherein said (C1-6)alkyl, heteroaryl, or phenyl is optionally substituted with one to three same or different halogens or one to three methyl groups; heteroaryl is selected from the group consisting of furanyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrazolyl, tetrazolyl, triazolyl, pyridinyl, pyrazinyl, pyridazinyl, and pyrimidinyl; heteroalicyclic is selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, N-methyl piperazine, piperidine, tetrahydrofuran, tetrahydropyran, azepine and morpholine;
K is selected from the group consisting of (C1-3)alkyl, hydroxy, (C1-3)alkoxy, halogen and —NR26R27; wherein said (C1-6)alkyl is optionally substituted with one to three same or different halogens;
R8, R9 and R28 are selected from the group consisting of hydrogen and (C1-6)alkyl;
X is selected from the group consisting of NR31, O and S;
R23, R24, R25, R26, R27, R29, R30, R31 are independently selected from the group consisting of hydrogen, (C1-6)alkyl, (C1-6)alkoxy, phenyl and heteroaryl; wherein said (C1-6)alkyl, phenyl, and heteroaryl are independently optionally substituted with one to three same or different group J; heteroaryl is selected from the group consisting of furanyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrazolyl, tetrazolyl, triazolyl, pyridinyl, pyrazinyl, pyridazinyl, and pyrimidinyl;
J is selected from the group consisting of (C1-6)alkyl, phenyl, heteroaryl, hydroxy, (C1-6)alkoxy, halogen, benzyl, —NR32C(O)—(C1-6)alkyl, —NR32R33, morpholino, nitro, —S(C1-6)alkyl, —SPh, NR32S(O)2—R33, piperazinyl, N-Me piperazinyl, (CH2)nCOOR28 and —CONR32R33; wherein said (C1-6)alkyl, heteroaryl, or phenyl is optionally substituted with one to three same or different halogens, amino, or methyl groups; heteroaryl is selected from the group consisting of furanyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrazolyl, tetrazolyl, triazolyl, pyridinyl, pyrazinyl, pyridazinyl, and pyrimidinyl; and
R32 and R33 are independently selected from the group consisting of hydrogen and (C1-6)alkyl; wherein said (C1-6)alkyl is optionally substituted with one to three same or different halogen, methyl, or CF3 groups.

### Claim 2 (depends on 1)

The method of claim 1, wherein in said compound
R1 is hydrogen;
-- represents a carbon-carbon bond; and
R6 does not exist.

### Claim 3 (depends on 2)

The method of claim 2, wherein in said compound
R7 is hydrogen; and
R15, R16, R17, R18, R19, R20, R21, R22 are each independently H or methyl with the proviso that a maximum of one of R15-R22 is methyl.

### Claim 4 (depends on 3)

The method of claim 3, wherein in said compound
Q is a member selected from groups (A) and (B) consisting of:
provided R2 and R3 are each independently hydrogen, methoxy or halogen; and
provided R2 is hydrogen, methoxy or halogen.

### Claim 5 (depends on 4)

The method of claim 4, wherein in said compound
Q is a member selected from groups (A), (B) and (C) consisting of:
provided R2 is hydrogen, methoxy or halogen;
R3 is hydrogen;
provided R2 and R3 are hydrogen; and
provided R2 is hydrogen, methoxy or halogen; and
R3 and R4 are hydrogen.

### Claim 6 (depends on 4)

The method of claim 4, wherein in said compound:
Q is
provided R2 is hydrogen, methoxy or halogen;
R3 is hydrogen; and
A is selected from the group consisting of phenyl and heteroaryl; wherein said phenyl and heteroaryl are each independently optionally substituted with one fluorine, hydroxy, methyl, or amino; and heteroaryl is selected from the group consisting of pyridinyl, furanyl and thienyl.

### Claim 7 (depends on 4)

The method of claim 4, wherein in said compound:
Q is
R2 and R3 are hydrogen; and
A is selected from the group consisting of phenyl and heteroaryl; wherein said phenyl and heteroaryl are each independently optionally substituted with one fluorine, hydroxy, methyl, or amino; and heteroaryl is selected from the group consisting of pyridinyl, furanyl and thienyl.

### Claim 8 (depends on 4)

The method of claim 4, wherein in said compound:
Q is
R2 is hydrogen, methoxy or halogen;
R3 and R4 are hydrogen; and
A is selected from the group consisting of phenyl and heteroaryl; wherein said phenyl and heteroaryl are each independently optionally substituted with one fluorine, hydroxy, methyl, or amino; and heteroaryl is selected from the group consisting of pyridinyl, furanyl and thienyl.

### Claim 9 (depends on 4)

The method of claim 4, wherein in said compound:
Q is:
R2 is hydrogen, methoxy or halogen;
R3 and R4 are hydrogen; and
A is selected from the group consisting of phenyl and heteroaryl; wherein said phenyl and heteroaryl are each independently optionally substituted with one flourine, hydroxy, methyl, or amino; and heteroaryl is selected from the group consisting of pyridinyl, furanyl and thienyl.

### Claim 10 (depends on 3)

The method of claim 3, wherein in said compound:
B is selected from the group consisting of —C(O)NR23R24, phenyl and heteroaryl;
wherein said phenyl or heteroaryl is optionally substituted with one to three same or different halogens or from one to two same or different substituents selected from the group F.

### Claim 11 (depends on 5)

The method of claim 5, wherein in said compound:
B is selected from the group consisting of —C(O)NR23R24, phenyl and heteroaryl; wherein said phenyl or heteroaryl is optionally substituted with one to three same or different halogens or from one to two same or different substituents selected from the group F.

### Claim 12 (depends on 6)

The method of claim 6, wherein in said compound:
B is selected from the group consisting of —C(O)NR23R24 phenyl and heteroaryl; wherein said phenyl or heteroaryl is optionally substituted with one to three same or different halogens or from one to two same or different substituents selected from the group F.

### Claim 13 (depends on 7)

The method of claim 7, wherein in said compound:
B is selected from the group consisting of —C(O)NR23R24, phenyl and heteroaryl; wherein said phenyl or heteroaryl is optionally substituted with one to three same or different halogens or from one to two same or different substituents selected from the group F.

### Claim 14 (depends on 9)

The method of claim 9, wherein in said compound:
B is selected from the group consisting of —C(O)NR23R24, phenyl and heteroaryl; wherein said phenyl or heteroaryl is optionally substituted with one to three same or different halogens or from one to two same or different substituents selected from the group F.

### Claim 15 (depends on 10)

The method of claim 10, wherein in said compound:
B is —C(O)NR23R24.

### Claim 16 (depends on 11)

The method of claim 11, wherein in said compound:
B is —C(O)NR23R24.

### Claim 17 (depends on 12)

The method of claim 12, wherein in said compound:
B is —C(O)NR23R24.

### Claim 18 (depends on 13)

The method of claim 13, wherein in said compound:
B is —C(O)NR23R24.

### Claim 19 (depends on 14)

The method of claim 14, wherein in said compound:
B is —C(O)NR23R24.