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Last Updated: March 29, 2024

Claims for Patent: 7,250,420


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Summary for Patent: 7,250,420
Title:Method of treatment of transplant rejection
Abstract: A method of treating or preventing chronic organ transplant rejection comprising administering a compound of the formula ##STR00001## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above.
Inventor(s): Changelian; Paul S. (East Greenwich, RI)
Assignee: Pfizer Inc. (New York, NY)
Application Number:10/720,600
Patent Claims:1. A method of treating chronic organ transplant rejection in a mammal, including a human, comprising administering to said mammal an amount of a compound of the formula ##STR00016## or the pharmaceutically acceptable salt thereof; wherein R.sup.1 is a group of the formula ##STR00017## wherein y is 0, 1 or 2; R.sup.4 is selected from the group consisting of hydrogen, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, nitro, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl or (C.sub.1-C.sub.6)acylamino; or R.sup.4 is (C.sub.3-C.sub.10)cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, nitro, nitro(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)acylamino; R.sup.5 is (C.sub.2-C.sub.9)heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five carboxy, cyano, amino, deuterium, hydroxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, halo, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkylamino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6) alkynyl, (C.sub.1-C.sub.6)alkylamino, amino(C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acyloxy(C.sub.1-C.sub.6)alkyl, nitro, cyano(C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, nitro(C.sub.1-C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)acylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)acylamino, amino(C.sub.1-C.sub.6)acyl, amino(C.sub.1-C.sub.6)acyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)acyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-S(O).sub.m, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m (C.sub.1-C.sub.6)alkyl, R.sup.15S(O).sub.m R.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1-C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1-C.sub.6)alkyl; or a group of the formula ##STR00018## wherein a is 0, 1, 2, 3 or 4; b, c, e, f and g are each independently 0 or 1; d is 0, 1, 2, or 3; X is S(O).sub.n wherein n is 0, 1 or 2; oxygen, carbonyl or --C(.dbd.N-cyano)-; Y is S(O).sub.n wherein n is 0, 1 or 2; or carbonyl; and Z is carbonyl, C(O)O--, C(O)NR-- or S(O).sub.n wherein n is 0, 1 or 2; R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are each independently selected from the group consisting of hydrogen or (C.sub.1-C.sub.6)alkyl optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, nitro, nitro(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)acylamino; R.sup.12 is carboxy, cyano, amino, oxo, deuterium, hydroxy, trifluoromethyl, (C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, halo, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2 amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, (C.sub.1-C.sub.6)alkylamino, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acyloxy(C.sub.1-C.sub.6)alkyl, nitro, cyano(C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, nitro(C.sub.1-C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)acylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)acylamino, amino(C.sub.1-C.sub.6)acyl, amino(C.sub.1-C.sub.6)acyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)acyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1-C.sub.6)alkyl R.sup.15C(O)NH, R.sup.15OC(O)NH, R.sup.15NHC(O)NH, (C.sub.1-C.sub.6)alkyl-S(O).sub.m, (C.sub.1-C.sub.6)alkyl-S(O).sub.m--(C.sub.1-C.sub.6)alkyl, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m (C.sub.1-C.sub.6)alkyl, R.sup.15S(O).sub.m R.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1-C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1-C.sub.6)alkyl; R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen, deuterium, amino, halo, hydoxy, nitro, carboxy, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, trifluoromethyl, trifluoromethoxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, (C.sub.3-C.sub.10)cycloalkyl wherein the alkyl, alkoxy or cycloalkyl groups are optionally substittued by one to three groups selected from halo, hydroxy, carboxy, amino (C.sub.1-C.sub.6)alkylthio, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl, (C.sub.3-C.sub.9)cycloalkyl or (C.sub.6-C.sub.10)aryl; or R.sup.2 and R.sup.3 are each independently (C.sub.3-C.sub.10)cycloalkyl, (C.sub.3-C.sub.10)cycloalkoxy, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.6-C.sub.10)arylamino, (C.sub.1-C.sub.6)alkylthio, (C.sub.6-C.sub.10)arylthio, (C.sub.1-C.sub.6)alkylsulfinyl, (C.sub.6-C.sub.10)arylsulfinyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.6-C.sub.10)arylsulfonyl, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl or (C.sub.6-C.sub.10)aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-CO--NH--, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, carboxy(C.sub.1-C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.6-C.sub.10)aryl, amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.6-C.sub.10)aryl(C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)alkyl, hydroxy, (C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonyl, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5-C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.6-C.sub.10)arylamino-CO--NH--, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.6-C.sub.10)arylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.6-C.sub.10)arylsulfonyl, (C.sub.6-C.sub.10)arylsulfonylamino, (C.sub.6-C.sub.10)arylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroaryl or (C.sub.2-C.sub.9)heterocycloalkyl; effective in treating such a condition.

2. A method according to claim 1, wherein a is 0; b is 1; X is carbonyl; c is 0; d is 0; e is 0; f is 0; and g is 0.

3. A method according to claim 1, wherein a is 0; b is 1; X is carbonyl; c is 0; d is 1; e is 0; f is 0, and g is 0.

4. A method according to claim 1, wherein a is 0; b is 1; X is carbonyl; c is 1; d is 0; e is 0; f is 0; and g is 0.

5. A method according to claim 1, wherein a is 0; b is 1; X is --C(.dbd.N=cyano)-; c is 1; d is 0; e is 0; f is 0; and g is 0.

6. A method according to claim 1, wherein a is 0; b is 0; c is 0; d is 0; e is 0; f is 0; g is 1; and Z is --C(O)--O--.

7. A method according to claim 1, wherein a is 0; b is 1; X is S(O).sub.n; n is 2; c is 0; d is 0; e is 0; f is 0; and g is 0.

8. A method according to claim 1, wherein a is 0; b is 1; X is S(O).sub.n; n is 2; c is 0; d is 2; e is 0; f is 1; g is 1; and Z is carbonyl.

9. A method according to claim 1, wherein a is 0; b is 1; X is S(O).sub.n; n is 2; c is 0; d is 2; e is 0; f is 1; and g is 0.

10. A method according to claim 1, wherein a is 0; b is 1; X is carbonyl; c is 1; d is 0; e is 1; Y is S(O).sub.n; n is 2; f is 0; and g is 0.

11. A method according to claim 1, wherein a is 0; b is 1; X is S(O).sub.n; n is 2; c is 1; d is 0; e is 0; f is 0; and g is 0.

12. A method according to claim 1, wherein R.sup.12 is cyano, trifluoromethyl, (C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.2-C.sub.6)alkynyl, cyano(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-S(O).sub.m wherein m is 0, 1 or 2.

13. A method according to claim 1, wherein said compound is selected from the group consisting of: Methyl-[4-methyl-1-(propane-1-sulfonyl)-piperidin-3-yl]-(7H-pyrrolo[2,3-d- ]pyrimidin-4-yl)-amine; 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-- carboxylic acid methyl ester; 3,3,3-Trifluoro-1-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-a- mino]-piperidin-1-yl}-propan-1-one; 4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-1-- carboxylic acid dimethylamide; ({4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidine-- 1-carbonyl}-amino)-acetic acid ethyl ester; 3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-- 1-yl}-3-oxo-propionitrile; 3,3,3-Trifluoro-1-{4-methyl-3-[methyl-(5-methyl-7H-pyrrolo[2,3-d]pyrimidi- n-4-yl)-amino]-piperidin-1-yl}-propan-1-one; 1-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-- 1-yl}-but-3-yn-1-one; 1-{3-[(5-Chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-methyl-p- iperidin-1-yl}-propan-1-one; 1-{3-[(5-Fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-methyl-p- iperidin-1-yl}-propan-1-one; N-cyano-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-N'-pr- opyl-piperidine-1-carboxamidine; N-cyano-4,N',N'-Trimethyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-ami- no]-piperidine-1-carboxamidine; Methyl-[(3R,4R)-4-methyl-1-(propane-1-sulfonyl)-piperidin-3-yl]-(7H-pyrro- lo[2,3-d]pyrimidin-4-yl)-amine; (3R,4R)-)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-pip- eridine-1-carboxylic acid methyl ester; 3,3,3-Trifluoro-1-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin- -4-yl)-amino]-piperidin-1-yl}-propan-1-one; (3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piper- idine-1-carboxylic acid dimethylamide; {(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-pipe- ridine-1-carbonyl}-amino)-acetic acid ethyl ester; 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-pi- peridin-1-yl}-3-oxo-propionitrile; 3,3,3-Trifluoro-1-{(3R,4R)-4-methyl-3-[methyl-(5-methyl-7H-pyrrolo[2,3-d]- pyrimidin-4-yl)-amino]-piperidin-1-yl}-propan-1-one; 1-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-pi- peridin-1-yl}-but-3-yn-1-one; 1-{(3R,4R)-3-[(5-Chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-- methyl-piperidin-1-yl}-propan-1-one; 1-{(3R,4R)-3-[(5-Fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-methyl-amino]-4-- methyl-piperidin-1-yl}-propan-1-one; (3R,4R)--N-cyano-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-ami- no]-N'-propyl-piperidine-1-carboxamidine; and (3R,4R)--N-cyano-4,N',N'-Trimethyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-- 4-yl)-amino]-piperidine-1-carboxamidine or pharmaceutically acceptable salt thereof.

14. A method of treating acute organ transplant rejection in a mammal, including a human, comprising administering to said mammal an amount of a compound of the formula ##STR00019## or the pharmaceutically acceptable salt thereof; wherein R.sup.1 is a group of the formula ##STR00020## wherein y is 0, 1 or 2; R.sup.4 is selected from the group consisting of hydrogen, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, nitro, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl or (C.sub.1-C.sub.6)acylamino; or R.sup.4 is (C.sub.3-C.sub.10)cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, nitro, nitro(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)acylamino; R.sup.5 is (C.sub.2-C.sub.9)heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five carboxy, cyano, amino, deuterium, hydroxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, halo, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkylamino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, (C.sub.1-C.sub.6)alkylamino, amino(C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acyloxy(C.sub.1-C.sub.6)alkyl, nitro, cyano(C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, nitro(C.sub.1-C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)acylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)acylamino, amino(C.sub.1-C.sub.6)acyl, amino(C.sub.1-C.sub.6)acyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)acyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-S(O).sub.m, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m (C.sub.1-C.sub.6)alkyl, R.sup.15S(O).sub.m R.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1-C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1-C.sub.6)alkyl; or a group of the formula ##STR00021## wherein a is 0, 1, 2, 3 or 4; b, c, e, f and g are each independently 0 or 1; d is 0, 1, 2, or 3; X is S(O).sub.n wherein n is 0, 1 or 2; oxygen, carbonyl or --C(.dbd.N-cyano)-; Y is S(O).sub.n wherein n is 0, 1 or 2; or carbonyl; and Z is carbonyl, C(O)O--, C(O)NR-- or S(O).sub.n wherein n is 0, 1 or 2; R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are each independently selected from the group consisting of hydrogen or (C.sub.1-C.sub.6)alkyl optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, nitro, nitro(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)acylamino; R.sup.12 is carboxy, cyano, amino, oxo, deuterium, hydroxy, trifluoromethyl, (C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, halo, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2 amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, (C.sub.1-C.sub.6)alkylamino, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acyloxy(C.sub.1-C.sub.6)alkyl, nitro, cyano(C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, nitro(C.sub.1-C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)acylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)acylamino, amino(C.sub.1-C.sub.6)acyl, amino(C.sub.1-C.sub.6)acyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)acyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1-C.sub.6)alkyl, R.sup.15C(O)NH, R.sup.15OC(O)NH, R.sup.15NHC(O)NH, (C.sub.1-C.sub.6)alkyl-S(O).sub.m, (C.sub.1-C.sub.6)alkyl-S(O).sub.m--(C.sub.1-C.sub.6)alkyl, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m (C.sub.1-C.sub.6)alkyl, R.sup.15S(O).sub.m R.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1-C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1-C.sub.6)alkyl; R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen, deuterium, amino, halo, hydroxy, nitro, carboxy, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, trifluoromethyl, trifluoromethoxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, (C.sub.3-C.sub.10)cycloalkyl wherein the alkyl, alkoxy or cycloalkyl groups are optionally substituted by one to three groups selected from halo, hydroxy, carboxy, amino (C.sub.1-C.sub.6)alkylthio, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl, (C.sub.3-C.sub.9)cycloalkyl or (C.sub.6-C.sub.10)aryl; or R.sup.2 and R.sup.3 are each independently (C.sub.3-C.sub.10)cycloalkyl, (C.sub.3-C.sub.10)cycloalkoxy, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.6-C.sub.10)arylamino, (C.sub.1-C.sub.6)alkylthio, (C.sub.6-C.sub.10)arylthio, (C.sub.1-C.sub.6)alkylsulfinyl, (C.sub.6-C.sub.10)arylsulfinyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.6-C.sub.10)arylsulfonyl, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl or (C.sub.6-C.sub.10)aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-CO--NH--, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, carboxy(C.sub.1-C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.6-C.sub.10)aryl, amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.6-C.sub.10)aryl(C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)alkyl, hydroxy, (C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonyl, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5-C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.6-C.sub.10)arylamino-CO--NH--, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.6-C.sub.10)arylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.6-C.sub.10)arylsulfonyl, (C.sub.6-C.sub.10)arylsulfonylamino, (C.sub.6-C.sub.10)arylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroaryl or (C.sub.2-C.sub.9)heterocycloalkyl; effective in treating such a condition.

15. A pharmaceutical composition for treating chronic organ transplant rejection in a mammal, including a human, comprising an amount of a compound of the formula ##STR00022## or the pharmaceutically acceptable salt thereof; wherein R.sup.1 is a group of the formula ##STR00023## wherein y is 0, 1 or 2; R.sup.4 is selected from the group consisting of hydrogen, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.4)alkoxy, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, nitro, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl or (C.sub.1-C.sub.6)acylamino; or R.sup.4 is (C.sub.3-C.sub.10)cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, nitro, nitro(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)acylamino; R.sup.5 is (C.sub.2-C.sub.9)heterocycloalkyl wherein the heterocycloalkyl groups must be substituted by one to five carboxy, cyano, amino, deuterium, hydroxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, halo, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkylamino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, (C.sub.1-C.sub.6)alkylamino, amino(C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acyloxy(C.sub.1-C.sub.6)alkyl, nitro, cyano(C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, nitro(C.sub.1-C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)acylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)acylamino, amino(C.sub.1-C.sub.6)acyl, amino(C.sub.1-C.sub.6)acyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)acyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-S(O).sub.m, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m (C.sub.1-C.sub.6)alkyl, R.sup.15S(O).sub.m R.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1-C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1-C.sub.6)alkyl; or a group of the formula ##STR00024## wherein a is 0, 1, 2, 3 or 4; b, c, e, f and g are each independently 0 or 1; d is 0, 1, 2, or 3; X is S(O).sub.n wherein n is 0, 1 or 2; oxygen, carbonyl or --C(.dbd.N-cyano)-; Y is S(O).sub.n wherein n is 0, 1 or 2; or carbonyl; and Z is carbonyl, C(O)O--, C(O)NR-- or S(O), wherein n is 0, 1 or 2; R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are each independently selected from the group consisting of hydrogen or (C.sub.1-C.sub.6)alkyl optionally substituted by deuterium, hydroxy, amino, trifluoromethyl, (C.sub.1-C.sub.6)acyloxy, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, cyano, cyano(C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, nitro, nitro(C.sub.1-C.sub.6)alkyl or (C.sub.1-C.sub.6)acylamino; R.sup.12 is carboxy, cyano, amino, oxo, deuterium, hydroxy, trifluoromethyl, (C.sub.1-C.sub.6)alkyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, halo, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2 amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, (C.sub.1-C.sub.6)alkylamino, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acyloxy(C.sub.1-C.sub.6)alkyl, nitro, cyano(C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, nitro(C.sub.1-C.sub.6)alkyl, trifluoromethyl, trifluoromethyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)acylamino, (C.sub.1-C.sub.6)acylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)acylamino, amino(C.sub.1-C.sub.6)acyl, amino(C.sub.1-C.sub.6)acyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)acyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)acyl, R.sup.15R.sup.16N--CO--O--, R.sup.15R.sup.16N--CO--(C.sub.1-C.sub.6)alkyl, R.sup.15C(O)NH, R.sup.15OC(O)NH, R.sup.15NHC(O)NH, (C.sub.1-C.sub.6)alkyl-S(O).sub.m, (C.sub.1-C.sub.6)alkyl-S(O).sub.m--(C.sub.1-C.sub.6)alkyl, R.sup.15R.sup.16NS(O).sub.m, R.sup.15R.sup.16NS(O).sub.m (C.sub.1-C.sub.6)alkyl, R.sup.15S(O).sub.m R.sup.16N, R.sup.15S(O).sub.mR.sup.16N(C.sub.1-C.sub.6)alkyl wherein m is 0, 1 or 2 and R.sup.15 and R.sup.16 are each independently selected from hydrogen or (C.sub.1-C.sub.6)alkyl; R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen, deuterium, amino, halo, hydroxy, nitro, carboxy, (C.sub.2-C.sub.6)alkenyl, (C.sub.2-C.sub.6)alkynyl, trifluoromethyl, trifluoromethoxy, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, (C.sub.3-C.sub.10)cycloalkyl wherein the alkyl, alkoxy or cycloalkyl groups are optionally substituted by one to three groups selected from halo, hydroxy, carboxy, amino (C.sub.1-C.sub.6)alkylthio, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl, (C.sub.3-C.sub.9)cycloalkyl or (C.sub.6-C.sub.10)aryl; or R.sup.2 and R.sup.3 are each independently (C.sub.3-C.sub.10)cycloalkyl, (C.sub.3-C.sub.10)cycloalkoxy, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.6-C.sub.10)arylamino, (C.sub.1-C.sub.6)alkylthio, (C.sub.6-C.sub.10)arylthio, (C.sub.1-C.sub.6)alkylsulfinyl, (C.sub.6-C.sub.10)arylsulfinyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.6-C.sub.10)arylsulfonyl, (C.sub.1-C.sub.6)acyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--, (C.sub.5-C.sub.9)heteroaryl, (C.sub.2-C.sub.9)heterocycloalkyl or (C.sub.6-C.sub.10)aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkyl-CO--NH--, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--(C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, carboxy(C.sub.1-C.sub.6)alkoxy, benzyloxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkoxy, (C.sub.6-C.sub.10)aryl, amino, amino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.6-C.sub.10)aryl(C.sub.1-C.sub.6)alkoxycarbonylamino, (C.sub.1-C.sub.6)alkylamino, ((C.sub.1-C.sub.6)alkyl).sub.2amino, (C.sub.1-C.sub.6)alkylamino(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino(C.sub.1-C.sub.6)alkyl, hydroxy, (C.sub.1-C.sub.6)alkoxy, carboxy, carboxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxycarbonyl, (C.sub.1-C.sub.6)alkoxycarbonyl(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy-CO--NH--, (C.sub.1-C.sub.6)alkyl-CO--NH--, cyano, (C.sub.5-C.sub.9)heterocycloalkyl, amino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--, (C.sub.6-C.sub.10)arylamino-CO--NH--, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--, (C.sub.1-C.sub.6)alkylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, ((C.sub.1-C.sub.6)alkyl).sub.2amino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.6-C.sub.10)arylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroarylamino-CO--NH--(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.6-C.sub.10)arylsulfonyl, (C.sub.6-C.sub.10)arylsulfonylamino, (C.sub.6-C.sub.10)arylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkylsulfonylamino, (C.sub.1-C.sub.6)alkylsulfonylamino(C.sub.1-C.sub.6)alkyl, (C.sub.5-C.sub.9)heteroaryl or (C.sub.2-C.sub.9)heterocycloalkyl, effective in such disorders or conditions and a pharmaceutically acceptable carrier.

16. A method according to claim 1, wherein the compound is 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-pi- peridin-1-yl}-3-oxo-propionitrile or a pharmaceutically acceptable salt thereof.

17. A method according to claim 14, wherein the compound is 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-pi- peridin-1-yl }-3-oxo-propionitrile or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition according to claim 15, wherein the compound is 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-pi- peridin-1-yl}-3-oxo-propionitrile or a pharmaceutically acceptable salt thereof.

19. A method according to claim 1, wherein the compound is administered in combination with one or more additional agents which modulate a mammalian immune system or with antiinflammatory agents.

20. A method according to claim 14, wherein the compound is administered in combination with one or more additional agents which modulate a mammalian immune system or with antiinflammatory agents.

21. A method according to claim 16, wherein the compound is administered in combination with one or more additional agents which modulate a mammalian immune system or with antiinflammatory agents.

22. A method according to claim 17, wherein the compound is administered in combination with one or more additional agents which modulate a mammalian immune system or with antiinflammatory agents.

23. A method according to claim 19, wherein the one or more additional agents is selected from the group consisting of cyclosporin A, rapamycin, tacrolimus, leflunomide, deoxyspergualin, mycophenolate mofetil, azathioprine, daclizumab, muromonab-CD3, antithymocyte globulin, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, prednisolone and dexamethasone.

24. A method according to claim 20, wherein the one or more additional agents is selected from the group consisting of cyclosporin A, rapamycin, tacrolimus, leflunomide, deoxyspergualin, mycophenolate mofetil, azathioprine, daclizumab, muromonab-CD3, antithymocyte globulin, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, prednisolone and dexamethasone.

25. A method according to claim 21, wherein the one or more additional agents is selected from the group consisting of cyclosporin A, rapamycin, tacrolimus, leflunomide, deoxyspergualin, mycophenolate mofetil, azathioprine, daclizumab, muromonab-CD3, antithymocyte globulin, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, prednisolone and dexamethasone.

26. A method according to claim 22, wherein the one or more additional agents is selected from the group consisting of cyclosporin A, rapamycin, tacrolimus, leflunomide, deoxyspergualin, mycophenolate mofetil, azathioprine, daclizumab, muromonab-CD3, antithymocyte globulin, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, prednisolone and dexamethasone.

Details for Patent 7,250,420

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Centocor Ortho Biotech Products, L.p. ORTHOCLONE OKT3 muromanab-cd3 Injection 103463 09/14/1992 ⤷  Try a Trial 2022-11-26
Hoffmann-la Roche Inc. ZENAPAX daclizumab Injection 103749 12/10/1997 ⤷  Try a Trial 2022-11-26
Biogen Inc. ZINBRYTA daclizumab Injection 761029 05/27/2016 ⤷  Try a Trial 2022-11-26
Biogen Inc. ZINBRYTA daclizumab Injection 761029 05/26/2017 ⤷  Try a Trial 2022-11-26
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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