Patent US5346893A successfully refreshed from Google Patents.
US5346893A
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Rapamycin 42-sulfonates and 42-(N-carbalkoxy) sulfamates useful as immunosuppressive agents
Assignee: Wyeth LLC
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Filing: 1993-05-19
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Granted: 1994-09-13
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Expires: 2013-05-19
Abstract
Abstract The invention concerns compounds of formula (I) ##STR1## where R 1 is alkyl, haloalkyl, alkenyl, or alkynyl containing 1 to 6 carbon atoms; or an aromatic moiety selected from phenyl, naphthyl and 4-(phenylaza) phenyl wherein said aromatic group is optionally substituted by one or more substituents selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, amino, mono- or di-(C 1 -C 6 )alkylamino, carboxy, (C 1 -C 6 alkoxy)carbonyl, C 2 -C 7 alkanoyl, (C 1 -C 6 ) thioalkyl, halo, cyano, nitro, trifuluoromethyl, trifluoromethoxy or R 1 is a heteroaromatic group of 5 to 10 ring atoms containing oxygen, nitrogen and/or sulfur as heteroatom(s) wherein said heteroaromatic group is optionally substituted by one or more substituents selected form C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, amino, mono- or di-(C 1 -C 6 )alkylamino, carboxy, (C 1 -C 6 alkoxy)carbonyl, C 2 -C 7 alkanoyl, (C 1 -C 6 ) thioalkyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy or R 1 is NHCO 2 R 2 wherein R 2 is lower alkyl containing 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof, which compounds are useful in the treatment of transplantation rejection, host versus graft disease, autoimmune diseases and diseases of inflammation.
Inventors
- 👤 Amedeo Failli
- 👤 Wenling Kao
- 👤 Robert J. Steffan
- 👤 Robert L. Vogel
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 12:30
CPC Classifications
C; C07; C07D; C07D498/00; C07D498/12; C07D498/18
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
198 words
A compound of formula (I) ##STR6## where R 1 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl; or an aromatic moiety selected from phenyl, naphthyl and 4-(phenylaza) phenyl wherein said aromatic group is optionally substituted by one or more substituents selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, amino, mono- or di-(C 1 -C 6 )alkylamino, carboxy, (C 1 -C 6 alkoxy)carbonyl, C 2 -C 7 alkanoyl, (C 1 -C 6 ) thioalkyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy or R 1 is a heteroaromatic group of 5 to 10 ring atoms containing oxygen, nitrogen or sulfur as heteroatom wherein said heteroaromatic group is optionally substituted by one or more substituents selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, amino, mono- or di-(C 1 -C 6 )alkylamino, carboxy, (C 1 -C 6 alkoxy)carbonyl, C 2 -C 7 alkanoyl, (C 1 -C 6 ) thioalkyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy or R 1 is NHCO 2 R 2 wherein R 2 is lower alkyl containing 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
198 words
A compound of formula (I) ##STR6## where R 1 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl; or an aromatic moiety selected from phenyl, naphthyl and 4-(phenylaza) phenyl wherein said aromatic group is optionally substituted by one or more substituents selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, amino, mono- or di-(C 1 -C 6 )alkylamino, carboxy, (C 1 -C 6 alkoxy)carbonyl, C 2 -C 7 alkanoyl, (C 1 -C 6 ) thioalkyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy or R 1 is a heteroaromatic group of 5 to 10 ring atoms containing oxygen, nitrogen or sulfur as heteroatom wherein said heteroaromatic group is optionally substituted by one or more substituents selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, amino, mono- or di-(C 1 -C 6 )alkylamino, carboxy, (C 1 -C 6 alkoxy)carbonyl, C 2 -C 7 alkanoyl, (C 1 -C 6 ) thioalkyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy or R 1 is NHCO 2 R 2 wherein R 2 is lower alkyl containing 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
190 words
A compound of claim 1 wherein R 1 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl; or an aromatic moiety selected from phenyl, naphthyl and 4-(phenylaza)phenyl wherein said aromatic group is optionally substituted by one or more substituents selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, amino, mono- or di(C 1 -C 6 ) alkylamino, carboxy, (C 1 -C 6 alkoxy)carbonyl, C 2 -C 7 alkanoyl, thioalkyl (C 1 -C 6 ), halo, cyano, nitro, trifluoromethyl, trifluoromethoxy or R 1 is a heteroaromatic moiety selected from thienyl, quinolinyl and isoquinolinyl wherein said heteroaromatic group is optionally substituted by one or more substituents selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, amino, mono- or di(C 1 -C 6 ) alkylamino, carboxy, (C 1 -C 6 alkoxy)carbonyl, C 2 -C 7 alkanoyl, thioalkyl (C 1 -C 6 ), halo, cyano, nitro, trifluoromethyl, trifluoromethoxy or R.sup. 1 is NHCO 2 R 2 wherein R 2 is lower alkyl containing 1 to 6 carbon atoms or a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is 5-(dimethylamino)-1-naphthyl or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is 4-methylphenyl or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is 2-thiophenyl or a pharmaceutically acceptable salt thereof.
Claim 7
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is 4-[[4-(dimethylamino)phenyl]aza]phenyl or a pharmaceutically acceptable salt thereof.
Claim 8
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is 1-naphthyl or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is 8-quinolinyl or a pharmaceutically acceptable salt thereof.
Claim 10
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is methyl or a pharmaceutically acceptable salt thereof.
Claim 11
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is 2,2,2-trifluoroethyl or a pharmaceutically acceptable salt thereof.
Claim 12
Dependent Claim
16 words
A compound of claim 1 wherein R 1 is [methoxycarbonyl]amino or a pharmaceutically acceptable salt thereof.
Claim 13
Dependent Claim
119 words
A process for preparing a compound of formula I as shown and defined in claim 1, which comprises: a) reacting rapamycin with a compound of formula R.sup.1 SO.sub.2 hal (II) or (R.sup.1 SO.sub.2).sub.2 O (III) wherein R 1 is as defined in claim 1 and hal is a halogen; b) reacting rapamycin with a compound of formula R.sup.2 OCON.sup.- SO.sub.2 N.sup.+ (alkyl).sub.3 (IV) wherein R 2 is as defined in claim 1 to give a corresponding compound of formula I where R 1 is NHCO 2 R 2 where R 2 is as defined above and if desired after each of the abovementioned processes isolating the compound of formula I in the form of a pharmaceutically acceptable salt thereof.
Claim 14
Dependent Claim
25 words
A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof as claimed in claim 1 and a pharmaceutically acceptable carrier.
Claim 15
Dependent Claim
37 words
A method of treating transplantation rejection, host versus graft disease, autoimmune diseases, and diseases of inflammation in a mammal by administering an effective amount of a compound of formula I as shown and defined in claim 1.
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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) | 1997-09-12 | 1998-03-14 | 1998-09-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-09-12 | 2002-03-14 | 2002-09-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-09-12 | 2006-03-14 | 2006-09-13 | $7700.00 | Window Closed / Lapsed |