US5120726A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Rapamycin hydrazones
Assignee: Wyeth LLC
•
Filing: 1991-03-08
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Granted: 1992-06-09
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Expires: 2011-03-08
Abstract
Abstract A compound of the structure ##STR1## wherein R 1 is hydrogen, alkyl or aralkyl; R 2 is hydrogen, alkyl, cycloalkyl, aralkyl, --COR 3 , --CO 2 R 3 , --SO 2 R 3 , --CONR 4 R 5 , --CSNR 4 R 5 , --COCONR 4 R 5 , or Ar; R 3 is alkyl, aralkyl, or Ar; R 4 and R 5 are each, independently, hydrogen, alkyl, cycloalkyl, allyl, aralkyl, or Ar; Ar is ##STR2## R 6 , R 7 , R 8 are each, independently, hydrogen, alkyl, alkoxy, hydroxy, cyano, halo, nitro, carbalkoxy, trifluoromethyl, trifluoromethoxy, amino, or a carboxylic acid; X is CH or N; Y is NH, O, or S; or a pharmaceutically acceptable salt thereof, which by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases and diseases of inflammation; by virtue of its antitumor activity is useful in treating solid tumors; and by virtue of its antifungal activity is useful in treating fungal infections.
Inventors
- 👤 Amedeo A. Failli
- 👤 Robert J. Steffan
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 14:52
CPC Classifications
C; C07; C07D; C07D498/00; C07D498/12; C07D498/18
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
170 words
A compound of the formula ##STR7## wherein R 1 is hydrogen, alkyl of 1-6 carbon atoms, or phenylalkyl of 7-10 carbon atoms; R 2 is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-10 carbon atoms, phenylalkyl 7-10 carbon atoms, --COR 3 , --CO 2 R 3 , --SO 2 R 3 , --CONR 4 R 5 , --CSNR 4 R 5 , --COCONR 4 R 5 , or Ar; R 3 is alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, or Ar; R 4 and R 5 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-10 carbon atoms, allyl, phenylalkyl of 7-10 carbon atoms, or Ar; Ar is ##STR8## R 6 , R 7 , R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, cyano, halo, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, trifluoromethoxy, amino, or --CO 2 H; X is CH or N; Y is NH, O, or S; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
170 words
A compound of the formula ##STR7## wherein R 1 is hydrogen, alkyl of 1-6 carbon atoms, or phenylalkyl of 7-10 carbon atoms; R 2 is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-10 carbon atoms, phenylalkyl 7-10 carbon atoms, --COR 3 , --CO 2 R 3 , --SO 2 R 3 , --CONR 4 R 5 , --CSNR 4 R 5 , --COCONR 4 R 5 , or Ar; R 3 is alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, or Ar; R 4 and R 5 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-10 carbon atoms, allyl, phenylalkyl of 7-10 carbon atoms, or Ar; Ar is ##STR8## R 6 , R 7 , R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, cyano, halo, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, trifluoromethoxy, amino, or --CO 2 H; X is CH or N; Y is NH, O, or S; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
16 words
A compound of claim 1 where R 1 is hydrogen or a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim
19 words
A compound of claim 1 where R 2 is --CONR 4 R 5 or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
24 words
A compound of claim 1 where R 1 is hydrogen and R 2 is --CONR 4 R 5 or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
29 words
A compound of claim 1 where R 1 is hydrogen, R 2 is --CONR 4 R 5 , and R 5 is Ar or a pharmaceutically acceptable salt thereof.
Claim 7
Dependent Claim
17 words
A compound of claim 1 where R 2 is --COR 3 or a pharmaceutically acceptable salt thereof.
Claim 8
Dependent Claim
22 words
A compound of claim 1 where R 1 is hydrogen and R 2 is --COR 3 or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
16 words
A compound of claim 1 where R 2 is Ar or a pharmaceutically acceptable salt thereof.
Claim 10
Dependent Claim
21 words
A compound of claim 1 where R 1 is hydrogen and R 2 is Ar or a pharmaceutically acceptable salt thereof.
Claim 11
Dependent Claim
24 words
A compound of claim 1 where R 1 is hydrogen, R 2 is Ar, and Ar is ##STR9## or a pharmaceutically acceptable salt thereof.
Claim 12
Dependent Claim
15 words
A compound of claim 1 which is rapamycin 27-(methylcarbonylhydrazone) or a pharmaceutically acceptable salt thereof.
Claim 13
Dependent Claim
15 words
A compound of claim 1 which is rapamycin 27-(4-phenylsemicarbazone) or a pharmaceutically acceptable salt thereof.
Claim 14
Dependent Claim
15 words
A compound of claim 1 which is rapamycin 27-(2-pyridinylhydrazone), or a pharmaceutically acceptable salt thereof.
Claim 15
Dependent Claim
15 words
A compound of claim 1 which is rapamycin 27-semicarbazone or a pharmaceutically acceptable salt thereof.
Claim 16
Dependent Claim
15 words
A compound of claim 1 which is rapamycin 27-hydrazone or a pharmaceutically acceptable salt thereof.
Claim 17
Independent Claim
196 words
A method of treating transplantation rejection, host vs. graft disease, autoimmune diseases, and diseases of inflammation in a mammal by administering an effective amount of a compound having the formula ##STR10## wherein R 1 is hydrogen, alkyl of 1-6 carbon atoms, or phenylalkyl of 7-10 carbon atoms; R 2 is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-10 carbon atoms, phenylalkyl of 7-10 carbon atoms, --COR 3 , --CO 2 R 3 , --SO 2 R 3 , --CONR 4 R 5 , --CSNR 4 R 5 , --COCONR 4 R 5 , or Ar; R 3 is alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, or Ar; R 4 and R 5 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-10 carbon atoms, allyl, phenylalkyl of 7-10 carbon atoms, or Ar; Ar is ##STR11## R 6 , R 7 , R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, cyano, halo, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, trifluoromethoxy, amino, or --CO 2 H; X is CH or N; Y is NH, O, or S; or a pharmaceutically acceptable salt thereof.
Claim 18
Independent Claim
196 words
A method of treating transplantation rejection, host vs. graft disease, autoimmune diseases, and diseases of inflammation in a mammal by administering an effective amount of a compound having the formula ##STR10## wherein R 1 is hydrogen, alkyl of 1-6 carbon atoms, or phenylalkyl of 7-10 carbon atoms; R 2 is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-10 carbon atoms, phenylalkyl of 7-10 carbon atoms, --COR 3 , --CO 2 R 3 , --SO 2 R 3 , --CONR 4 R 5 , --CSNR 4 R 5 , --COCONR 4 R 5 , or Ar; R 3 is alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, or Ar; R 4 and R 5 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-10 carbon atoms, allyl, phenylalkyl of 7-10 carbon atoms, or Ar; Ar is ##STR11## R 6 , R 7 , R 8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, cyano, halo, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, trifluoromethoxy, amino, or --CO 2 H; X is CH or N; Y is NH, O, or S; or a pharmaceutically acceptable salt thereof.
Claim 19
Dependent Claim
19 words
A pharmaceutical composition for use as an immunosuppressive agent comprising an immunosuppressive amount of a compound of claim 1.
Claim 20
Dependent Claim
11 words
A composition as claimed in claim 17 in unit dosage form.
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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) | 1995-06-09 | 1995-12-09 | 1996-06-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-06-09 | 1999-12-09 | 2000-06-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-06-09 | 2003-12-09 | 2004-06-09 | $7700.00 | Window Closed / Lapsed |