# US 5,348,960 A · Imidazo[4,5-b]quinolinyl oxy alkyl tetrazolyl piperidine derivatives

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- Number: US 5,348,960 A
- Document ID: US5348960A
- Status: Granted
- Kind: A
- Application number: 08/114,262
- Filed: 1993-08-30
- Granted: 1994-09-20
- Earliest claimed: 1992-04-03
- Assignees: Bristol-Myers Squibb Company
- Inventors: Piyasena Hewawasam; Nicholas A. Meanwell
- Web page: https://patentgrep.com/patent/US5348960A

## CPC

- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

A series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones having enhanced water solubility bioavailability and metabolic stability is disclosed in the Formula I ##STR1## wherein R.sup.1 is H, or C.sub.1 -C.sub.4 lower alkyl; R.sup.2 is H, or (CH.sub.2).sub.m R.sup.3 ; R.sup.3 is tetrahydro-2H-pyranyl, C.sub.1 -C.sub.8 alkyl, C.sub.4 -C.sub.8 cycloalkyl, or substituted or unsubstituted phenyl, wherein the substituents are halogen, alkoxy, or trifluoromethyl; m is an integer of 1-3; and n is an integer of 1-5; or pharmaceutically acceptable salt thereof. The compounds are useful as inhibitors of ADP-induced blood platelet aggregation in human platelet-rich plasma.

## Claims

### Claim 1

A compound of the formula ##STR37## wherein R.sup.1 is H, or C.sub.1 -C.sub.4 lower alkyl;
R.sup.2 is H, or (CH.sub.2).sub.m R.sup.3 ;
R.sup.3 is tetrahydro-2H-pyranyl, C.sub.1 -C.sub.8 alkyl, C.sub.4 -C.sub.8 cycloalkyl, or substituted or unsubstituted phenyl, wherein the substituents are halogen, alkoxy, or trifluoromethyl;
m is an integer of 1-3; and
n is an integer of 1-5;
or pharmaceutically acceptable salt thereof.

### Claim 2

The intermediate compound which is ethyl 4-[5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)propyl]-1H-te trazol-1-yl]-1-piperidinecarboxylate.

### Claim 3 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)propyl]-1H-tetr azol-1-yl]piperidine or pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) propyl]-1H-tetrazol-1-yl]-1-(phenylmethyl)piperidine or pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) propyl]-1H-tetrazol-l-yl]-l-[(4-fluorophenyl)methyl]piperidine or pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The compound of claim 1 which is (cyclohexylmethyl)-4-[5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7- yloxy)propyl]-1H-tetrazol-1yl]piperidine or pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) propyl]-1H-tetrazol-l-yl]-l-(2-ethylbut-1-yl) piperidine or pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) propyl]-1H-tetrazol-l-yl]-l-(2-methylprop-1-yl) piperidine or pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) propyl]-1H-tetrazol-l-yl]-l-(2-phenylethyl) piperidine or pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The compound of claim 1 which is 1-cyclopentylmethyl-4-[5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7 -yloxy)propyl]-1H-tetrazol-1-yl]piperidine or pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

The compound of claim 1 which is 1-cycloheptylmethyl-4-[5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7 -yl-oxy)propyl]-1H-tetrazol-1-yl]piperidine or pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) propyl]-1H-tetrazol-1-yl]-1-(2-propylpent-1-yl) piperidine or pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The compound of claim 1, which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo [4,5-b]quinoline-7-yloxy)propyl[-1H-tetrazol-1-yl]-1[(tetrahydro-2H-pyran- 2-yl)methyl] piperidine or pharmaceutically acceptable salt thereof.

### Claim 14

The intermediate compound which is ethyl 4-[5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b] quinolin-7-yloxy)butyl]-1H-tetrazol-1-yl]-1-piperidine carboxylate.

### Claim 15 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-]quinolin-7-yloxy) butyl]-1H-tetrazol-1-yl]piperidine or pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) butyl]-1H-tetrazol-1-yl]-1-(phenylmethyl) piperidine or pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The compound of claim 1, which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo [4,5-b] quinolin-7-yloxy)butyl]-1H-tetrazole-1-yl]-1-[(4-fluorophenyl)methyl]piper idine or pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 1)

The compound of claim 1 which is 1-cyclohexylmethyl-4-[5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7- yloxy)butyl]-1H-tetrazol-1yl]piperidine or pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) butyl]-1H-tetrazol-l-yl]-l-(2-ethylbutyl) piperidine or pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 1)

The compound of claim 1 which is [5-[3-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy) butyl]-1H-tetrazol-l-yl]-l-(2-methylpropyl) piperidine or pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 1)

A method for inhibiting blood platelet aggregation in a mammal which comprises administering a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 1)

The pharmaceutical composition for inhibiting blood platelet aggregation comprising a, therapeutically effective amount of a compound of claim 1 of a pharmaceutically acceptable acid addition salt thereof and a pharmaceutical carrier.