US5346893A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Rapamycin 42-sulfonates and 42-(N-carbalkoxy) sulfamates useful as immunosuppressive agents
Assignee: Wyeth LLC
•
Filing: 1993-05-19
•
Granted: 1994-09-13
•
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 11:28
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.
References Cited (Backward Citations)
US3993749A
Cited
US4885171A
Cited
US4316885A
Cited
US4401653A
Cited
US5130307A
Cited
US5078999A
Cited
US5080899A
Cited
US5120842A
Cited
US5120842B1
Cited
EP0507555A1
Cited
US5100883A
Cited
US5118678A
Cited
US5102876A
Cited
US5118677A
Cited
EP0525960A1
Cited
US5138051A
Cited
US5169851A
Cited
US5151413A
Cited
US5194447A
Cited
US5177203A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 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 |