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Generated: September 20, 2017

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Title:Pyrazolyl substituted pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
Abstract: The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines of Formula I: ##STR00001## that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.
Inventor(s): Rodgers; James D. (Landenberg, PA), Shepard; Stacey (Wilmington, DE), Maduskuie; Thomas P. (Wilmington, DE), Wang; Haisheng (Hockessin, DE), Falahatpisheh; Nikoo (Wilmington, DE), Rafalski; Maria (Greenville, DE), Arvanitis; Argyrios G. (Kennett Square, PA), Storace; Louis (Middletown, DE), Jalluri; Ravi Kumar (Avondale, PA)
Assignee: Incyte Corporation (Wilmington, DE)
Application Number:12/138,082
Patent Claims: 1. A compound of Formula II: ##STR00729## or a pharmaceutically acceptable salt thereof, wherein: X is N; n is 1and Y is C.sub.1-8 alkylene, C.sub.2-8 alkenylene, (CR.sup.11R.sup.12).sub.pC(O)(CR.sup.11R.sup.12).sub.q, (CR.sup.11R.sup.12).sub.pC(O)NR.sup.C(CR.sup.11R.sup.12).sub.q, (CR.sup.11R.sup.12).sub.pC(O)O(CR.sup.11R.sup.12).sub.q,or (CR.sup.11R.sup.12).sub.pOC(O)(CR.sup.11R.sup.12).sub.q, wherein said C.sub.1-8 alkylene or C.sub.2-8 alkenylene is optionally substituted with 1, 2,or 3 halo, OH, CN, amino, C.sub.1-4 alkylamino, or C.sub.2-8 dialkylamino; Z is aryl, cycloalkyl, heteroaryl, or heterocycloalkyl, each optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from halo, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.1-4 haloalkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4, cyanoalkyl, Cy.sup.1, CN, NO.sub.2, OR.sup.a, SR.sup.a, C(O )R.sup.b, C(O)NR.sup.cR.sup.d, C(O)OR.sup.a, OC(O)R.sup.b, OC(O)NR.sup.cR.sup.d, NR.sup.cR.sup.d, NR.sup.cC(O)R.sup.b, NR.sup.cC(O)NR.sup.cR.sup.d, NR.sup.cC(O)OR.sup.a, S(O)R.sup.b, S(O)NR.sup.cR.sup.d, S(O).sub.2R.sup.b, NR.sup.cS(O).sub.2R.sup.b, and S(O).sub.2NR.sup.cR.sup.d; Cy.sup.1 is independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.1-4 haloalkyl, C.sub.1-4 cyanoalkyl, CN, NO.sub.2, OR.sup.a'', SR.sup.a'', C(O)R.sup.b'', C(O)NR.sup.c''R.sup.d'', C(O)OR.sup.a'', OC(O)R.sup.b'', OC(O)NR.sup.c''R.sup.d'', NR.sup.c''R.sup.d'', NR.sup.c''C(O)R.sup.b'', NR.sup.c''C(O)OR.sup.a'',NR.sup.c''S(O)R.sup.b'', NR.sup.c''S(O).sub.2R.sup.b'', S(O)R.sup.b'', S(O)NR.sup.c''R.sup.d'', S(O ).sub.2R.sup.b'', and S(O).sub.2NR.sup.c''R.sup.d''; R.sup.1, R.sup.2, and R.sup.3 are each H; R.sup.11 and R.sup.12 are independently selected from H, halo, OH, CN, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 cyanoalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl; R.sup.a and R.sup.a'' are independently selected from H, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl and heterocycloalkylalkyl, wherein said C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl; R.sup.b and R.sup.b'' are independently selected from H, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl and heterocycloalkylalkyl, wherein said C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl; R.sup.c and R.sup.d are independently selected from H, C.sub.1-10 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl and heterocycloalkylalkyl, wherein said C.sub.1-10 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; or R.sup.c and R.sup.d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl; R.sup.c'' and R.sup.d'' are independently selected from H, C.sub.1-10 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl and heterocycloalkylalkyl, wherein said C.sub.1-10 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl; or R.sup.c'' and R.sup.d'' together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl; p is 0, 1, 2, 3, 4, 5, or 6; and q is 0, 1, 2, 3, 4, 5 or 6.

2. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein n is 1 and Y is C.sub.1-8 alkylene, (CR.sup.11R.sup.12).sub.pC(O)(CR.sup.11R.sup.12).sub.q, (CR.sup.11R.sup.12).sub.pC(O)NR.sup.c(CR.sup.11R.sup.12).sub.q, or (CR.sup.11R.sup.12).sub.pC(O)O(CR.sup.11R.sup.12).sub.q, wherein said C.sub.1-8 alkylene is optionally substituted with 1, 2, or 3 halo, OH, CN, amino, C.sub.1-4 alkylamino, or C.sub.2-8 dialkylamino.

3. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein n is 1 and Y is C.sub.1-8 alkylene optionally substituted with 1, 2, or 3 halo, OH, CN, amino, C.sub.1-4 alkylamino, or C.sub.2-8 dialkylamino.

4. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein n is 1 and Y is (CR.sup.11R.sup.12).sub.pC(O)(CR.sup.11R.sup.12).sub.q (CR.sup.11R.sup.12).sub.pC(O)NR.sup.c(CR.sup.11R.sup.12).sub.q, or (CR.sup.11R.sup.12).sub.pC(O)O(CR.sup.11R.sup.12).sub.q.

5. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein p is 0.

6. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein p is 1.

7. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein p is 2.

8. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein q is 0.

9. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein q is 1.

10. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein q is 2.

11. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein one of p and q is 0 and the other of p and q is 1,2, or 3.

12. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Z is substituted with 1, 2, 3, 4, 5, or 6 independently selected substituents, wherein at least one of said substituents comprises at least one CN group.

13. A composition comprising a compound of claim 1, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

14. The composition of claim 13 which is suitable for topical administration.

15. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein Z is cycloalkyl, optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from halo, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, C.sub.1-4 haloalkyl, C.sub.1-4 hydroxyalkyl, C.sub.1-4 cyanoalkyl, Cy.sup.1, CN, NO.sub.2, OR.sup.a, SR.sup.a, C(O)R.sup.b, C(O)NR.sup.cR.sup.d, C(O)OR.sup.a, OC(O)R.sup.b, OC(O)NR.sup.cR.sup.d, NR.sup.cR.sup.d, NR.sup.cC(O)R.sup.b, NR.sup.cC(O)NR.sup.cR.sup.d, NR.sup.cC(O)OR.sup.a, S(O)R.sup.b, S(O)NR.sup.cR.sup.d, S(O).sub.2R.sup.b, NR.sup.cS(O).sub.2R.sup.b, and S(O).sub.2NR.sup.cR.sup.d.

16. The compound of claim 1, selected from: 4-{1-[pyrrolidin-2-ylmethyl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidine- ; 4-(1-[1-(methylsulfonyl)pyrrolidin-2-yl]methyl-1H-pyrazol-4-yl)-7H-pyrro- lo[2,3-d]-pyrimidine; 4-[1-(1-cyclopentylpropyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidine; 3-{(2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}- benzonitrile; 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-(3-thienyl)prop- anenitrile; 3-(3-furyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propan- enitrile; and 3-pyridin-4-yl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pro- panenitrile; or a pharmaceutically acceptable salt of any of the aforementioned.

17. The compound of claim 1, selected from: 3-cyclohexyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propa- nenitrile; 4-cyclopropyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]butanenitrile; 3-(2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl)-- cyclopentane-carbonitrile; 3-[3-(hydroxymethyl)cyclopentyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1- H-pyrazol-1-yl]-propanenitrile; 3-pyridin-3-yl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pro- panenitrile; 3-[4-(methylthio)phenyl]-3-[4-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-(3-methoxyphenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-y- l]propanenitrile; 3-(4-methoxyphenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-y- l]propanenitrile; 3-[4-(methylsulfinyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]-propanenitrile; 3-[4-(methylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]-propanenitrile; 3-[3-(cyanomethoxy)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyra- zol-1-yl]-propanenitrile; 3-(6-chloropyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazo- l-1-yl]propanenitrile; 5-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}p- yridine-2-carbonitrile; 3-(3,5-dimethylisoxazol-4-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-p- yrazol-1-yl]-propanenitrile; 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- 1-yl]-3-[6-(trifluoromethyl)pyridin-3-yl]-propanenitrile; 3-(6-methoxypyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyraz- ol-1-yl]propane-nitrile; 3-pyridin-2-yl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pro- panenitrile; 3-(6-bromopyridin-2-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]propanenitrile; 6-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}p- yridine-2-carbonitrile; 3-(5-bromopyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]propanenitrile; 5-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}n- icotinonitrile; 3-(2-methoxypyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyraz- ol-1-yl]propane-nitrile; 3-[4-(cyanomethoxy)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyra- zol-1-yl]propane-nitrile; 3-[2-(cyanomethoxy)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyra- zol-1-yl]-propanenitrile; 3-(3,5-dibromophenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1- -yl]propanenitrile; 5-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}i- sophthalonitrile; 3-[6-(dimethylamino)pyridin-2-yl]-3-[4-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-propanenitrile; 3-(4-bromo-2-thienyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1- -yl]propanenitrile; 5-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}t- hiophene-3-carbonitrile; 3-(5-bromo-2-fluorophenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyra- zol-1-yl]-propanenitrile; 3-(3-nitrophenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]- propanenitrile; 3-(5-bromo-2-methoxyphenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyr- azol-1-yl]-propanenitrile; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- 4-methoxybenzo-nitrile; 3-(3-bromophenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]- propanenitrile; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- 4-fluorobenzonitrile; 3-[5-bromo-2-(cyanomethoxy)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- -1H-pyrazol-1-yl]-propanenitrile; 3-(4-bromo-2-furyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-y- l]propanenitrile; 4-(cyanomethoxy)-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyr- azol-1-yl]ethyl}-benzonitrile; 3-(4-bromopyridin-2-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]propanenitrile; 2-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}i- sonicotinonitrile; 5-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- 3-furonitrile; 3-[2-bromo-5-(cyanomethoxy)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- -1H-pyrazol-1-yl]-propanenitrile; 4-(cyanomethoxy)-2-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyr- azol-1-yl]-ethyl}benzonitrile; 3-pyrimidin-5-yl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]p- ropanenitrile; 3-(2-bromopyridin-4-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]propanenitrile; 4-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}p- yridine-2-carbo-nitrile; 3-(5-methoxypyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyraz- ol-1-yl]propane-nitrile; 3-(3-chlorophenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl- ]propanenitrile; 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-[3-(trifluorome- thyl)phenyl]-propanenitrile; 3-(3-phenoxyphenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-y- l]propanenitrile; 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-[3-(trifluorome- thoxy)-phenyl]-pronenitrile; methyl 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}b- enzoate; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl- ]ethyl}benzoic acid; 3-[3-(1H-pyrazol-4-yl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-p- yrazol-1-yl]-propanenitrile; 3-(3-aminophenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]- propanenitrile; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)acetamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-methanesulfonamide; 4-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}t- hiophene-2-carbonitrile; 5-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}t- hiophene-2-carbonitrile; 3-[3-(morpholin-4-ylcarbonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-y- l)-1H-pyrazol-1-yl]-propanenitrile; N-(2-aminoethyl)-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyr- azol-1-yl]ethyl}-benzamide; 3-(5-formyl-3-thienyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-- 1-yl]propanenitrile; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-methylbenzamide; 2-cyano-N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1- -yl]ethyl}phenyl)-acetamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-nicotinamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-N'-isopropylurea; isopropyl (3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}- phenyl)-carbamate; 3-(5-phenylpyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazo- l-1-yl]propanenitrile; 3-(3,3`-bipyridin-5-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]propanenitrile; 3-(5-pyrimidin-5-ylpyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1- H-pyrazol-1-yl]-propanenitrile; 3-[5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrim- idin-4-yl)-1H-pyrazol-1-yl]propanenitrile; and 3-(5-ethynylpyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyraz- ol-1-yl]propane-nitrile; or a pharmaceutically acceptable salt of any of the aforementioned.

18. The compound of claim 1, selected from: 3-[5-(phenylthio)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-- pyrazol-1-yl]-propanenitrile; 3-(2-bromo-1,3-thiazol-5-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]-propanenitrile; 3-(5-morpholin-4-ylpyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1- H-pyrazol-1-yl]-propanenitrile; 3-(1-methyl-1H-pyrazol-4-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]-propanenitrile; 3-(3-pyridin-3-ylphenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazo- l-1-yl]propanenitrile; 3-[5-(phenylsulfinyl)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- -1H-pyrazol-1-yl]-propanenitrile; 3-[5-(phenylsulfonyl)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- -1H-pyrazol-1-yl]-propanenitrile; 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-[5-(1,3-thiazol- -2-ylthio)pyridin-3-yl]propanenitrile; 3-[5-(ethylthio)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-p- yrazol-1-yl]-propanenitrile; 4-{1-[1-methyl-2-(1H-1,2,4-triazol-1-yl)ethyl]-1H-pyrazol-4-yl}-7H-pyrrol- o[2,3-d]pyrimidine; 1-phenyl-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propan-1-- one; 3-[5-(ethylsulfinyl)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-- yl)-1H-pyrazol-1-yl]-propanenitrile; 3-[5-(ethylsulfonyl)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-- 1H-pyrazol-1-yl]-propanenitrile; 3-[5-(cyclohexylthio)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- -1H-pyrazol-1-yl]-propanenitrile; 1-phenyl-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propan-1-- ol; 3-[3-(ethylthio)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyra- zol-1-yl]propanenitrile; 3-[3-(ethylsulfinyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyr- azol-1-yl]-propanenitrile; 3-[3-(ethylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyr- azol-1-yl]-propanenitrile; 3-[5-(cyclohexylsulfonyl)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]-pyrimidin-- 4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-[5-(cyclohexylsulfinyl)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4- -yl)-1H-pyrazol-1-yl]propanenitrile; 4-[1-(1-methyl-2-phenylethyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin- e; 4-{1-[1-methyl-2-(3-thienyl)ethyl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]py- rimidine; 3-{1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}- benzonitrile; 4-{1-[2-(1H-imidazol-1-yl)-1-methylethyl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3- -d]pyrimidine; 4-{1-[1-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1H-pyrazol-4-yl}-7- H-pyrrolo[2,3-d]-pyrimidine; 3-[3-(methylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]-propanenitrile; 3-(3-pyridin-4-ylphenyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazo- l-1-yl]propanenitrile; 3-[5-(isopropylthio)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-- 1H-pyrazol-1-yl]-propanenitrile; 3-[5-(isopropylsulfinyl)pyridin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-- yl)-1H-pyrazol-1-yl]propanenitrile; 3-[5-(isopropylsulfonyl)pyridin-3-yl]3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-y- l)-1H-pyrazol-1-yl]propanenitrile; 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-[5-(trifluorome- thyl)pyridin-3-yl]-propanenitrile; 2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-N-[3-(trifluorome- thyl)phenyl]-propanamide; N-2-naphthyl-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propa- namide; N-1-naphthyl-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-y- l]propanamide; N-(3-cyanophenyl)-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]- propanamide; N-phenyl-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanamid- e; N-(4-phenoxyphenyl)-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1- -yl]butanamide; N-2-naphthyl-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butan- amide; N-(3-cyanophenyl)-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]butanamide; N-biphenyl-4-yl-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]bu- tanamide; N-(biphenyl-4-ylmethyl)-2-[4-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanamide; N-(biphenyl-3-ylmethyl)-2-[4-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanamide; N-(4-cyanophenyl)-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]- butanamide; N-1-naphthyl-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butan- amide; 5-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]e- thyl}-N-phenylnicotin-amide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-3-(trifluoromethyl)benzamide; N-(3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methyl}phenyl)- -3-(trifluoro-methyl)benzamide; 3-[3-(methylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]-propanenitrile; N-(3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methyl}phenyl)- benzene-sulfonamide; 3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methyl}-N-[3-(tri- fluoromethyl)-phenyl]benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N,N-dimethyl-benzenesulfonamide; N-benzyl-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-y- l]ethyl}benzene-sulfonamide; N-benzyl-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-y- l]ethyl}benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-phenylbenzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-[3-(trifluoro-methyl)phenyl]benzamide; N-(3-cyanophenyl)-3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl- ]methyl}-benzamide; N-benzyl-3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methyl}b- enzamide; N-1-naphthyl-3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-- 1-yl]methyl}benzamide; N-2-naphthyl-3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]meth- yl}benzamide; N-(3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methyl}phenyl)- -2-naphthamide; N-(3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methyl}phenyl)- -1-naphthamide; 2-phenyl-N-(3-{[4-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methyl}phenyl)-acetamide; 3-chloro-N-(3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methy- l}phenyl)-benzamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-2-naphthamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-1-naphthamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-eth- yl}phenyl)-2-phenylacetamide; 3-cyano-N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1- -yl]ethyl}phenyl)-benzamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-benzamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-4-(trifluoromethyl)benzamide; N-(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethy- l}phenyl)-N`-phenylurea; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-[4-(trifluoro-methyl)phenyl]benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-(4-methyl-phenyl)benzamide; N-(4-cyanophenyl)-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]-ethyl}benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-2-naphthyl-benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-1-naphthyl-benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N,N-dimethyl-benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-pyridin-3-yl-benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-methyl-N-phenyl-benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-cyclohexyl-benzamide; N-(3-cyanophenyl)-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]ethyl}-benzamide; N-biphenyl-4-yl-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d ]pyrimidin-4-yl)-1H-pyrazol-1-yl]-ethyl}benzamide; N-(4-chlorophenyl)-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-p- yrazol-1-yl]-ethyl}benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-(3,4-dimethyl-phenyl)benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-isoxazol-3-yl-benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-methyl-N-phenylbenzenesulfonamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-propylbenzene-sulfonamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-phenyl-benzenesulfonamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-2-naphthyl-benzenesulfonamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-cyclopropyl-benzenesulfonamide; 3-[3-(piperidin-1-ylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-y- l)-1H-pyrazol-1-yl]-propanenitrile; 3-[3-(morpholin-4-ylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-y- l)-1H-pyrazol-1-yl]-propanenitrile; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-(4-methylphenyl)-benzenesulfonamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-(3,4-dimethyl-phenyl)benzenesulfonamide; 3-[3-(benzylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-py- razol-1-yl]-propanenitrile; 3-[3-(benzylthio)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazo- l-1-yl]propanenitrile; 4-{[(3-{2-cyano-1-[4-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}phenyl)-sulfonyl]methyl}benzonitr- ile; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]eth- yl}-N-methylbenzene-sulfonamide; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-1-naphthyl-benzenesulfonamide; N-biphenyl-4-yl-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyra- zol-1-yl]ethyl}-benzenesulfonamide; 3-[3-(benzyloxy)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]propanenitrile; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N-cyclohexyl-benzenesulfonamide; 3-[3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,- 3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}-- N,N-diethyl-benzenesulfonamide; 3-{3-[(4-ethylpiperazin-l-yl)sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d]-pyr- imidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; N-1,3-benzodioxo1-5-yl-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-- 1H-pyrazol-1-yl]-ethyl}benzenesulfonamide; 3-{3-[(2,6-dimethylmorpholin-4-yl)sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d- ]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-{3-[(4-oxopiperidin-1-yl)sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d]pyrimi- din-4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-[3-(isopropylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H- -pyrazol-1-yl]-propanenitrile; 3-{3-[(cyclohexylmethyl)sulfonyl]phenyl}-3-[4-(7H -pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-[3-(octahydroisoquinolin-2(1H)-ylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-- d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; and 3-{3-[(2-phenylethyl)-sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4- -yl)-1H-pyrazol-1-yl]propanenitrile; or a pharmaceutically acceptable salt of any of the aformentioned.

19. The compound of claim 1 selected from: 3-[3-(piperazin-l-ylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-y- l)-1H-pyrazol-1-yl]propanenitrile; 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-[3-(thiomorphol- in-4-ylsulfonyl)-phenyl]propanenitrile; 3-{3-[(4-hydroxypiperidin-1-yl)sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d]py- rimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-[3-(isobutylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2 ,3 -d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-propanenitrile; 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol -1-yl]-3-{3-[(tetrahydro-2H-pyran-4-ylmethyl)sulfonyl]phenyl}propanenitri- le; 3-{3-[(3-furylmethyl)sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin- -4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-{3-[(1,1-dioxidothiomorpholin-4-yl)sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,- 3-d]pyrimidin-4-yl)-1H-p yrazol-1-yl]propanenitrile; 3-{3-[(pyridin-4-ylmethyl)sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d]pyrimid- in-4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-{3-hydroxy-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-y 1)-1H-pyrazol-1-yl]propyl}-N,N-dimethyl-benzenesulfonamide; 3-{1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]but-3-en-1-yl}b- enzonitrile; 4-{1-[1-(3-bromophenyl)but-3-en-1-yl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]p- yrimidine; 3-{4,4-difluoro-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyraz- ol-1-yl]but-3-en-1-yl}-benzonitrile; 4-(1-{4,4-difluoro-1-[3-(morpholin-4-ylsulfonyl)phenyl]but-3-en-1-yl}-1H-- pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine; 4-(1-{1-[3-(ethylsulfonyl)phenyl]-4,4-difluorobut-3-en-1-yl}-1H-pyrazol-4- -yl)-7H-pyrrolo[2,3-d]pyrimidine; 4-(1-{1-[3-(benzyloxy)phenyl]-4,4-difluorobut-3-en-1-yl}-1H-pyrazol-4-yl)- -7H-pyrrolo[2,3-d]-pyrimidine; 4-(1-{4,4-difluoro-1-[3-(methylsulfonyl)phenyl]but-3-en-1-yl}-1H-pyrazol-- 4-yl)-7H-pyrrolo[2,3-d]pyrimidine; 3-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]methyl}benzonitri- le; 3-{1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butyl}benzon- itrile; 4-(1-{1-[3-(ethylsulfonyl)phenyl]-4,4-difluorobutyl}-1H-pyrazol-4-- yl)-7H-pyrrolo[2,3-d]-pyrimidine; 4-[1-(1-cyclopentylbut-3-en-1-yl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrim- idine; 4-[1-(1-cyclopentylbutyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimid- ine; 4-[1-(1-cyclopentyl-4,4-difluorobut-3-en-1-yl)-1H-pyrazol-4-yl]-7H-py- rrolo[2,3-d]pyrimidine; 4-1-[4,4-difluoro-1-(tetrahydrofuran-3-yl)but-3-en-1-yl]-1H-pyrazol-4-yl1- -7H-pyrrolo[2,3-d]pyrimidine; 4-[1-(1-cyclopropyl-4,4-difluorobut-3-en-1-yl)-1H-pyrazol-4-yl]-7H-pyrrol- o[2,3-d]pyrimidine; 4-[1-(1-cyclopentyl-4,4-difluorobutyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]- pyrimidine; 3-(1-methylcyclopentyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol- -1-yl]propanenitrile; 1-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}c- yclopropane-carbonitrile; 3-[1-(methylsulfonyl)pyrrolidin-3-yl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-- yl)-1H-pyrazol-1-yl]propanenitrile; 4-{1-[2,2,2-trifluoro-1-(1H-imidazol-2-ylmethyl)ethyl]-1H-pyrazol-4-yl}-7- H-pyrrolo[2,3-d]pyrimidine; 4-(1-(1R)-2,2,2-trifluoro-1-[(4-methyl-1,3 -thiazol-2-yl)methyl]ethyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine; 4-{1-[1-(5-bromopyridin-3-yl)-4,4-difluorobut-3-e n-1-yl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidine; 5-{4,4-difluoro-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]bu- t-3-en-1-yl}nicotinonitrile; 3-[3-(pyrrolidin-1-ylsulfonyl)phenyl]-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-- yl)-1H-pyrazol-1-yl]propanenitrile; N-benzyl-3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-y- l]ethyl}-N-methylbenzenesulfonamide; 3-{[(3-{2-cyano-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]et- hyl}-phenyl)sulfonyl]methyl}-benzonitrile; 3-{3-[(2-naphthylmethyl)-sulfonyl]-phenyl}-3-[4-(7H-pyrrolo[2,3-d]pyrimid- in-4-yl)-1H-pyrazol-1-yl]propanenitrile; 3-{3-[(1-phenylethyl)sulfonyl]-phenyl}-3-[4-(7H-pyrrolo[2,3-d]-pyrimidin-- 4-yl)-1H-pyrazol-1-yl]-propanenitrile; 3-{2-cyano-1-[4-(7H-pyrrolo-[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}- -N-(2-morpholin-4-ylethyl)-benzenesulfonamide; 3-{2-cyano-1-[4-(7H-pyrrolo-[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}- -N-[(1S)-1-phenylethyl]benzenesulfonamide; 3-{2-cyano-1-[4-(7H-pyrrolo-[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}- -N-phenyl-benzamide; 3-{2-cyano-1-[4-(7H-pyrrolo-[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}- -N-(tetrahydrofuran-2-yl-methyl)benzenesulfonamide; 3-{3-[(cyclopropylmethyl)sulfonyl]phenyl}-3-[4-(7 H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile trifluoroacetate; 3-{3-[(4-methylpiperazin-l-yl)-sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d]py- rimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; and 3-{3-[(1-oxidothiomorpholin-4-yl)sulfonyl]phenyl}-3-[4-(7H-pyrrolo[2,3-d]- pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; or a pharmaceutically acceptable salt of any of the aforementioned.

20. A compound of claim 1, wherein said compound is 3-cyclopropyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-propio- nitrile; or a pharmaceutically acceptable salt thereof.

21. The compound of claim 15, wherein Y is C.sub.1-8 alkylene optionally substituted with 1, 2, or 3 halo, OH, CN, amino, C.sub.1-4 alkylamino, or C.sub.2-8 dialkylamino.
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