Patent US4943573A successfully refreshed from Google Patents.
US4943573A
Expired / Lapsed
US
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Imidazo[4,5-b]quinolinyloxyalkanoic acid amides with enhanced water solubility
Assignee: Bristol Myers Squibb Co
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Filing: 1989-11-01
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Granted: 1990-07-24
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Expires: 2009-11-01
Abstract
Abstract A novel series of 2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolinyloxyalkanoic acid amides having enhanced water solubility is disclosed of the formula ##STR1## wherein n is 3 to 5; R 1 is alkyl of 1 to 4 carbon atoms; R 2 is hydrogen; R 3 is 1-piperidinylethyl, 1-benzylpiperidin-4-yl, 4-(1-piperidinyl)piperidine, (1-alkyl-2-pyrrolidinyl)alkyl where alkyl is 1 to 4 carbon atoms, 3-quinuclidinyl; R 2 and R 3 together with the nitrogen atom to which they are attached form 4-R 4 -piperazin-1-yl wherein R 4 is alkyl of 1 to 7 carbon atoms, alkoxyethyl of 3 to 7 carbon atoms, pyridinyl, pyrimidinyl, tetrahydropyranylmethyl, thienylmethyl, cycloalkyl-(CH 2 ) m where m is zero or one and cycloalkyl is 5 to 7 carbon atoms except m is zero when cycloalkyl is 7 carbon atoms, benzyl, 4-fluorobenzyl, 3-trifluoromethylbenzyl, 4-alkoxybenzyl where alkoxy is 1 to 4 carbon atoms. The compounds are cyclic AMP phosphodiesterase inhibitors and are particularly useful as inhibitors of blood platelet aggregation and/or as cardiotonic agents.
Inventors
- 👤 Nicholas A. Meanwell
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 13:32
CPC Classifications
C; C07; C07D; C07D487/00; C07D487/02; C07D487/04; C07D471/00; C07D471/02; C07D471/04; A; A61; A61P; A61P43/00; A61P7/00; A61P7/02
Claims Analysis
Total Claims: 38
Claim 1
Independent Claim
129 words
A compound of the formula ##STR45## wherein n is 3 to 5; R 1 is alkyl of 1 to 4 carbon atoms; R 2 is hydrogen: R 3 is 1-piperidinylethyl, 1-benzylpiperidin-4-yl, 4-(1-piperidinyl)piperidine, (1-alkyl-2pyrrolidinyl)alkyl where alkyl is 1 to 4 carbon atoms, 3-quinuclidinyl: R 2 and R 3 together with the nitrogen atom to which they are attached form 4-R 4 -piperazin-1-yl wherein R 4 is alkyl of 1 to 7 carbon atoms, alkoxyethyl of 3 to 7 carbon atoms, pyridinyl, pyrimidinyl, tetrahydropyranylmethyl, thienylmethyl, cycloalkyl(CH 2 ) m where m is zero or one and cycloalkyl is 5 to 7 carbon atoms except m is zero when cycloalkyl is 7 carbon atoms, benzyl, 4-fluorobenzyl, 3-trifluoromethylbenzyl, 4-alkoxybenzyl where alkoxy is 1 to 4 carbon atoms: or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
129 words
A compound of the formula ##STR45## wherein n is 3 to 5; R 1 is alkyl of 1 to 4 carbon atoms; R 2 is hydrogen: R 3 is 1-piperidinylethyl, 1-benzylpiperidin-4-yl, 4-(1-piperidinyl)piperidine, (1-alkyl-2pyrrolidinyl)alkyl where alkyl is 1 to 4 carbon atoms, 3-quinuclidinyl: R 2 and R 3 together with the nitrogen atom to which they are attached form 4-R 4 -piperazin-1-yl wherein R 4 is alkyl of 1 to 7 carbon atoms, alkoxyethyl of 3 to 7 carbon atoms, pyridinyl, pyrimidinyl, tetrahydropyranylmethyl, thienylmethyl, cycloalkyl(CH 2 ) m where m is zero or one and cycloalkyl is 5 to 7 carbon atoms except m is zero when cycloalkyl is 7 carbon atoms, benzyl, 4-fluorobenzyl, 3-trifluoromethylbenzyl, 4-alkoxybenzyl where alkoxy is 1 to 4 carbon atoms: or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
10 words
The compound of claim 1 wherein R 1 is hydrogen.
Claim 4
Dependent Claim
29 words
The compound of claim 1 wherein R 1 is hydrogen and R 3 and R 3 together with the nitrogen to which they are attached form 4-R 4 -piperazin-1-yl.
Claim 5
Dependent Claim
35 words
The compound of claim 3 wherein R 4 is cycloalkyl-(CH 2 ) m wherein m is zero or one and cycloalkyl is 5-7 carbon atoms except m is zero when cycloalkyl is 7 carbon atoms.
Claim 6
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 4-[2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yl)-oxy]-N-[2-(1-piperidinyl)ethyl]butanamide.
Claim 7
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 4-[(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yl)oxy]-N-[(1-ethyl-2pyrrolidinyl)methyl]butanamide.
Claim 8
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 4-[2,3-dihydro-2-oxo-1H-imidazo[4,5-b]-quinolin-7-yl)oxo]-N-[2-(1-methyl-2-pyrrolidinyl)ethyl]butanamide.
Claim 9
Dependent Claim
15 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 4-(2,3-dihydro-1-oxo-1H-imidazo [4,5-b]-quinolin-7-yloxy)-N-[1-(phenylmethyl)-4-piperidinyl)butanamide.
Claim 10
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is N-(1-azabicyclo[2.2.2]oct3-yl)-4-[2,3-dihydro-2-oxo-1H-imidazo[4,5-b]-quinolin-7-yl)oxy]butanamide.
Claim 11
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl]-4-(1piperidinyl)piperidine.
Claim 12
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-[(2,3-dihydro-2-oxo-1H-imidazo-[4,5-b]quinolin-7-yl)oxy]-1-oxobutyl]-4methylpiperazine.
Claim 13
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1Himidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl]-4-(2-methylpropyl)piperazine.
Claim 14
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1Himidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl]-4-(2-methoxyethy1)piperazine.
Claim 15
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-[2,3-dihydro-2-oxo-1Himidazo[4,5-b]-quinolin-7-yl)oxy]-1-oxobutyl]-4-phenylmethylpiperazine.
Claim 16
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[5-[2,3-dihydro-2-oxo-1Himidazo[4,5-b]-quinolin-7-yl]oxy]-1-oxopentyl]-4-phenylmethylpiperazine.
Claim 17
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1H-imidazo-(4,5-b)quinolin-7-yloxy)-1-oxobutyl]-4-[(4-fluorophenyl)methyl]-piperazine.
Claim 18
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]-quinolin-7-yloxy)-1-oxobutyl]-4-[[3-(trifluoro-methyl)phenyl]methyl]piperazine.
Claim 19
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]-quinolin-7-yloxy)-1-oxobutyl]-4-(4methoxyphenyl)methyl]piperazine.
Claim 20
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]-quinolin-7-yloxy)-1-oxobutyl]-4-(2thienylmethyl)piperazine.
Claim 21
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1-H-imidazo[4,5-b]-quinolin-7-yloxy)-1-oxobutyl]-4-(3-thienylmethyl)piperazine.
Claim 22
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1-H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl]-4-[tetrahydro-1H-pyran-2-yl)-ethyl]piperazine.
Claim 23
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1-imidazo-[4,5-b]quinolin-7-yloxy)-1-oxobutyl]-4-(2pyridinyl)piperazine.
Claim 24
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-[(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]-quinolin-7-yl)oxy]-1-oxobutyl]-4-(2pyrimidinyl)piperazine.
Claim 25
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-(cyclopentylmethyl)-4[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl-piperazine.
Claim 26
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-(cyclohexylmethyl)-4[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxybutyl]piperazine.
Claim 27
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-(cyclohexylmethyl)-4-[5-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxopentyl]-piperazine.
Claim 28
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-cycloheptanyl-4-[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl]piperazine.
Claim 29
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl]-4-[(2-ethyl)butyl]piperazine.
Claim 30
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-(cyclohexylmethyl)-4-[6-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxohexyl]piperazine.
Claim 31
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-[4-[2,3-dihydro-1-methyl-2-oxo-1H-imidazo[4,5-b]-quinolin-1-yl)oxy]-1-oxobutyl]-4-phenylmethyl-piperazine.
Claim 32
Dependent Claim
14 words
The compound of claim 1 or a pharmaceutically acceptable salt thereof which is 1-(cyclohexylmethyl)-4-[4-(2,3-dihydro-1-methyl-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl]piperazine.
Claim 33
Dependent Claim
29 words
A method for inhibiting cyclic AMP phosphodiesterase in a mammal which comprises administering a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.
Claim 34
Dependent Claim
36 words
A method for increasing heart inotropic activity which comprises administering to a warm blooded animal, in need of such treatment a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.
Claim 35
Dependent Claim
31 words
The pharmaceutical composition for inhibiting cyclic AMP phosphodiesterase comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutical carrier.
Claim 36
Dependent Claim
29 words
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 37
Dependent Claim
31 words
The pharmaceutical composition for inhibiting blood platelet aggregation comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutical carrier.
Claim 38
Dependent Claim
31 words
The pharmaceutical composition for increasing heart inotropic activity comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutical carrier.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-07-23 | 1994-01-22 | 1994-07-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-07-23 | 1998-01-22 | 1998-07-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-07-23 | 2002-01-22 | 2002-07-24 | $7700.00 | Window Closed / Lapsed |