Patent US5272163A successfully refreshed from Google Patents.
US5272163A
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US
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Therapeutic amides
Assignee: AstraZeneca UK Ltd
•
Filing: 1992-07-23
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Granted: 1993-12-21
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Expires: 2012-07-23
Abstract
Abstract Amides having formula I: ##STR1## wherein E, X, R 2 and R 3 have the meanings given in the specification, and pharmaceutically acceptable salts and pharmaceutically acceptable in vivo hydrolysable esters thereof, which are useful in the treatment of urinary incontinence. Further provided are processes for preparing the amides and pharmaceutical compositions containing them.
Inventors
- 👤 Keith Russell
- 👤 Cyrus J. Ohnmacht
- 👤 Keith H. Gibson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 18:27
CPC Classifications
C; C07; C07C; C07C317/00; C07C317/26; C07D; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/62; C07D213/70; A; A61; A61K; A61K31/00; A61K31/33; A61K31/38; A61P; A61P13/00; A61P13/02; A61P15/00; C07C235/00; C07C235/02; C07C235/04; C07C235/16; C07C317/32; C07C317/34; C07C317/38; C07C317/40; C07C317/44; C07C317/48; C07C317/50; C07D213/24; C07D213/44; C07D213/46; C07D213/50; C07D213/72; C07D213/75; C07D239/00; C07D239/02; C07D239/24; C07D239/28; C07D239/32; C07D239/38; C07D241/00; C07D241/02; C07D241/10; C07D241/14; C07D241/18; C07D277/00; C07D277/02; C07D277/20; C07D277/32; C07D277/36; C07D333/00; C07D333/02; C07D333/04; C07D333/26; C07D333/30; C07D333/34; C07C2601/00; C07C2601/06; C07C2601/08
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
161 words
An amide of the following formula XVII, wherein: Y is a linking group selected from sulfinyl and sulfonyl; Ar is selected from the group consisting of: six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms; and carbon-linked five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; provided that Ar is not 5-pyrimidinyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; and R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 ti 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.
Claim 2
Dependent Claim
161 words
An amide of the following formula XVII, wherein: Y is a linking group selected from sulfinyl and sulfonyl; Ar is selected from the group consisting of: six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms; and carbon-linked five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; provided that Ar is not 5-pyrimidinyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; and R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 ti 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.
Claim 3
Dependent Claim
43 words
An amide as claimed in claim 1 wherein: Ar is selected from the group consisting of 2-, 3-, and 4-pyridyl, 2- and 4-pyrimidinyl, 3- and 4-isothiazolyl, 2- and 4-oxazolyl, 2- and 4-thiazolyl, 2- and 3-furyl, and 2- and 3-thienyl; and Z is hydrogen.
Claim 4
Dependent Claim
57 words
An amide as claimed in claim 2, wherein: R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl.
Claim 5
Dependent Claim
20 words
An amide as claimed in claim 3, wherein: Ar is selected from the group consisting of 2-, 3-, and 4-pyridyl.
Claim 6
Dependent Claim
47 words
An amide as claimed in claim 4, wherein: R 2 and R 3 are independently selected from the group consisting of (i) R 2 is trifluoromethyl and R 3 is selected from methyl, ethyl, and trifluoromethyl; and (ii) R 2 is trifluoromethyl and R 3 is difluoromethyl.
Claim 7
Dependent Claim
16 words
An amide as claimed in claim 1, which is selected from: N-[4-(4-pyridylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; S(-)-N-[4-(4-pyridylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; N-4-(4-pyridylsulfonyl)phenyl]-3,3-difluoro-2-difluoromethylpropanamide; and N-[4-(4-pyridylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanamide.
Claim 8
Dependent Claim
21 words
A pharmaceutically acceptable salt or an in vivo hydrolyzable ester of an amide as claimed in any one of claims 1-6.
Claim 9
Dependent Claim
173 words
A pharmaceutical composition comprising an amide of the following formula XVII, ##STR3## wherein: Y is a linking group selected from sulfinyl and sulfonyl; Ar is selected from the group consisting of: six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms; and carbon-linked five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; provided that Ar is not 5-pyrimidinyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; and R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring; and a pharmaceutically acceptable diluent or carrier.
Claim 10
Dependent Claim
173 words
A pharmaceutical composition comprising an amide of the following formula XVII, ##STR3## wherein: Y is a linking group selected from sulfinyl and sulfonyl; Ar is selected from the group consisting of: six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms; and carbon-linked five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; provided that Ar is not 5-pyrimidinyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; and R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring; and a pharmaceutically acceptable diluent or carrier.
Claim 11
Dependent Claim
43 words
A composition as claimed in claim 8 wherein: Ar is selected from the group consisting of 2-, 3-, and 4-pyridyl, 2- and 4-pyrimidinyl, 3- and 4-isothiazolyl, 2- and 4-oxazolyl, 2- and 4-thiazolyl, 2- and 3-furyl, and 2- and 3-thienyl; and Z is hydrogen.
Claim 12
Dependent Claim
57 words
A composition as claimed in claim 9, wherein: R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl.
Claim 13
Dependent Claim
20 words
A composition as claimed in claim 10, wherein: Ar is selected from the group consisting of 2-, 3-, and 4-pyridyl.
Claim 14
Dependent Claim
47 words
A composition as claimed in claim 28, wherein: R 2 and R 3 are independently selected from the group consisting of (i) R 2 is trifluoromethyl and R 3 is selected from methyl, ethyl, and trifluoromethyl; and (ii) R 2 is difluoromethyl and R 3 is difluoromethyl.
Claim 15
Dependent Claim
19 words
A composition as claimed in claim 8, wherein said amide is selected from: N-[4-(4-pyridylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; S-(-)-N-[4-(4-pyridylsulfonyl)phenyl]- 3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; N-[4-(4-pyridylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethylpropanamide; and N-[4-(4-pyridylsulfonyl)phenyl]3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanamide.
Claim 16
Dependent Claim
29 words
A pharmaceutical composition as claimed in any one of claims 8-13 wherein said amide is in the form of a pharmaceutically acceptable salt or an in vivo hydrolyzable ester.
Claim 17
Independent Claim
183 words
A method of treating urinary incontinence, comprising administering to a mammal in need of such treatment an effective amount of an amide of the following formula XVII, ##STR4## wherein: Y is a linking group selected from sulfinyl and sulfonyl; and Ar is selected from the group consisting of: six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms; and carbon-linked five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; provided that Ar is not 5-pyrimidinyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; and R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.
Claim 18
Independent Claim
183 words
A method of treating urinary incontinence, comprising administering to a mammal in need of such treatment an effective amount of an amide of the following formula XVII, ##STR4## wherein: Y is a linking group selected from sulfinyl and sulfonyl; and Ar is selected from the group consisting of: six-membered heteroaryl rings containing 1-2 nitrogen atoms as the only heteroatoms; and carbon-linked five-membered heteroaryl rings containing from 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; provided that Ar is not 5-pyrimidinyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; and R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.
Claim 19
Dependent Claim
43 words
A method as claimed in claim 15 wherein: Ar is selected from the group consisting of 2-, 3-, and 4-pyridyl, 2- and 4-pyrimidinyl, 3- and 4-isothiazolyl, 2- and 4-oxazolyl, 2- and 4-thiazolyl, 2- and 3-furyl, and 2- and 3-thienyl; and Z is hydrogen.
Claim 20
Dependent Claim
57 words
A method as claimed in claim 16, wherein: R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl.
Claim 21
Dependent Claim
20 words
A method as claimed in claim 17, wherein: Ar is selected from the group consisting of 2-, 3-, and 4-pyridyl.
Claim 22
Dependent Claim
47 words
A method as claimed in claim 18, wherein: R 2 and R 3 are independently selected from the group consisting of (i) R 2 is trifluoromethyl and R 3 is selected from methyl, ethyl, and trifluoromethyl; and (ii) R 2 is difluoromethyl and R 3 is difluoromethyl.
Claim 23
Dependent Claim
18 words
A method as claimed in claim 15, wherein said amide is selected from: N-[4-(4-pyridylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; S-(-)-N-[4-(4-pyridylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; N-[4-(4-pyridylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethylpropanamide; and N-[4-(4-pyridylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanamide.
Claim 24
Independent Claim
28 words
A method as claimed in any one of claims 15-20 wherein said amide is in the form of a pharmaceutically acceptable salt or an in vivo hydrolyzable ester.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1996-12-20 | 1997-06-21 | 1997-12-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-12-20 | 2001-06-21 | 2001-12-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-12-20 | 2005-06-21 | 2005-12-21 | $7700.00 | Window Closed / Lapsed |