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ME02386B - Derivati piperidin-4-il azetidina kao inhibitori jak1 - Google Patents

Derivati piperidin-4-il azetidina kao inhibitori jak1

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Publication number
ME02386B
ME02386B MEP-2016-41A MEP4116A ME02386B ME 02386 B ME02386 B ME 02386B ME P4116 A MEP4116 A ME P4116A ME 02386 B ME02386 B ME 02386B
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Montenegro
Prior art keywords
azetidin
pyrazol
pyrimidin
piperidin
pyrrolo
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MEP-2016-41A
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German (de)
English (en)
French (fr)
Inventor
Taisheng Huang
Chu-Biao Xue
Anlai Wang
Ling Kong
Hai Fen Ye
Wenqing Yao
James D Rodgers
Stacey Shepard
Haisheng Wang
Lixin Shao
Hui-Yin Li
Qun Li
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Incyte Holdings Corp
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Application filed by Incyte Holdings Corp filed Critical Incyte Holdings Corp
Publication of ME02386B publication Critical patent/ME02386B/me

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Claims (24)

1. Jedinjenje Formule (I):ili njegova farmaceutski prihvatljiva so; pri čemu:X je N ili CR2;Y je N ili CR2;Z je H, cijano, halo, C1-3 alkil, ili C1-3 haloalkil;L je C(R4)2, C(=O), C(=O)N(R4a), C(=O)C(R4b)2, S(=O)2, C(=O)O, C(=O)OC(R4b)2 ili C(=O)N(R4a)C(R4b)2;A je C1-6 alkil, C3-14 cikloalkil, C2-13 heterocikloalkil, C6-14 aril, ili C1-14 heteroaril; pri čemu navedeni C1-6 alkil,C3-14 cikloalkil, C2-13 heterocikloalkil, C6-14 aril, i C1-14 heteroaril su svaki opciono supstitisani sa 1, 2, 3, 4, 5, ili 6 nezavisno izabranih R5 grupa;svaka R1 je, nezavisno, C1-4 alkil, hidroksil, C1-4 alkoksi, fluoro, hidroksi-C1-4 alkil, ili C1-4 alkoksi-C1-4 alkil; ilidve R1 grupe zajedno formiraju 2-člani- ili 3-člani ugljenikov most od formule -CH2-O-CH2-;R2 je H, halo, hidroksil, cijano, C1-4 alkil, C1-4 haloalkil, ili C1-4 alkoksi;R3 je H, cijano, nitro, halo, hidroksil, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-7 cikloalkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di-C1-6 alkilamino, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di-C1-6 alkilkarbamil, karboksi, C1-6 alkilkarbonil, ili C1-6 alkoksikarbonil;svaka R4 je, nezavisno, H ili C1-4 alkil; ilidve R4 grupe, zajedno sa atomom ugljenika na koji su vezane, formiraju 3-, 4-, 5-, ili 6-člani prsten cikloalkila;R4a je H ili C1-4 alkil;svaka R4b je, nezavisno, H ili C1-4 alkil; ilidve R4b grupe, zajedno sa atomom ugljenika na koji su vezane, formiraju 3-, 4-, 5-, ili 6- člani prsten cikloalkila;svaka R5 je, nezavisno, halo, cijano, nitro, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halosulfanil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, C1-10 heteroaril-C1-3 alkil, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(=NRe)Rb, C(=NRe)NRcRd, NRcC(=NRe)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, ili S(O)2NRcRd; pri čemu C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6grupa;svaka R6 je, nezavisno, halo, cijano, nitro, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halosulfanil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, C1-10 heteroaril-C1-3 alkil, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, ili S(O)2NRc1Rd1; pri čemu navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih Rh grupa;svaka Ra, Rb, Rc, i Rd je, nezavisno, H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, ili C1-10 heteroaril-C1-3 alkil; pri čemu navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil je opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih Rg groupa;ili bilo koja Rc i Rd zajedno sa atomom N na koji su vezane, formiraju 3-, 4-, 5-, 6-, ili 7-članu heterocikloalkil grupu ili heteroaril grupu, svaku opciono supstituisani sa 1, 2, 3 ili 4 supstituenata nezavisno izabrana od halo, cijano, nitro, hidroksil, C1-6 alkila, C2-6 alkenila, C2-6 alkinila, C3-7 cikloalkila, C1-6 haloalkila, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di-C1-6 alkilamino, tio, C1-6 alkiltio, C1-6 alkilsulfinila, C1-6 alkilsulfonila, karbamila, C1-6 alkilkarbamila, di-C1-6 alkilkarbamila, karboksi, C1-6 alkilkarbonila, i C1-6 alkoksikarbonila;svaka Re je, nezavisno, H, C1-6 alkil, CN, hidroksil, C1-6 alkoksi, C1-6 alkilsulfonil, karboksi, C1-6 alkilkarbonil,aminosulfonil, C1-6 alkilaminosulfonil, di-C1-6 alkilaminosulfonil, karbamil, C1-6 alkilkarbamil, ili di-C1-6 alkilkarbamil;svaka Ra1, Rb1, Rc1, i Rd1 je, nezavisno, H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, ili C1-10 heteroaril-C1-3 alkil; pri čemu navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil je opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih Rg’ grupa;ili bilo koja Rc1 i Rd1 zajedno sa atomom N na koji su vezane, formiraju 3-, 4-, 5-, 6-, ili 7-članu heterocikloalkil grupu ili heteroaril grupu, svaku opciono supstituisanu sa 1, 2, 3 ili 4 supstituenata nezavisno izabrana od halo, cijano, nitro, hidroksila, C1-6 alkila, C2-6 alkenila, C2-6 alkinila, C3-7 cikloalkila, C1-6 haloalkila, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di-C1-6 alkilamino, tio, C1-6 alkiltio, C1-6 alkilsulfinila, C1-6 alkilsulfonil, karbamila, C1-6 alkilkarbamila, di-C1-6 alkilkarbamila, karboksi, C1-6 alkilkarbonila, C1-6 alkoksikarbonila, i C1-6 alkilkarbonilamino;svaka Re1 je, nezavisno , H, C1-6 alkil, CN, hidroksil, C1-6 alkoksi, C1-6 alkilsulfonil, karboksi, C1-6 alkilkarbonila, aminosulfonila, C1-6 alkilaminosulfonila, di-C1-6 alkilaminosulfonila, karbamila, C1-6 alkilkarbamila, ili di-C1-6 alkilkarbamil;svaka Rg, Rg’, i Rh je, nezavisno, halo, cijano, nitro, hidroksil, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-7 cikloalkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di-C1-6 alkilamino, tio, C1-6 alkiltio, C1-6 alkilsulfinil, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di-C1-6 alkilkarbamil, karboksi, C1-6 alkilkarbonil, C1-6 alkoksikarbonil, ili C1-6 alkilkarbonilamino; in je 0, 1, 2, 3, ili 4.
2. Jedinjenje prema zahtevu 1, ili njegova farmaceutski prihvatljiva so, pri čemu: X je N ili CR2; Y je N ili CR3; Z je H, cijano, halo, C1-3 alkil, ili C1-3 haloalkil; L je C(R4)2, C(=O), C(=O)N(R4a), C(=O)C(R4b)2, ili S(=O)2; A je C1-6 alkil, C3-14 cikloalkil, C2-13 heterocikloalkil, C6-14 aril, ili C1-14 heteroaril; pri čemu navedeni C1-6 alkil, C3-14 cikloalkil, C2-13 heterocikloalkil, C6-14 aril, i C1-14 heteroaril su svaki opciono supstituisani sa 1, 2, 3, 4, 5, li 6 nezavisno izabranih R5 grupa; svaka R1 je, nezavisno, C1-4 alkil; ili dve R1 grupe zajedno formiraju dvočlani ili tročlani ugljenikov most; R2 je H, halo, hidroksil, cijano, C1-4 alkil, C1-4 haloalkil, ili C1-4 alkoksi; R3 je H, cijano, nitro, halo, hidroksil, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-7 cikloalkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di-C1-6 alkilamino, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di-C1-6 alkilkarbamil, karboksi, C1-6 alkilkarbonil, ili C1-6 alkoksikarbonil; svaka R4 je,nezavisno , H ili C1-4 alkil; ili dve R4 grupe, zajedno sa atomom ugljenika na koji su vezane, formiraju 3-, 4-, 5-, ili 6-člani prsten cikloalkila; R4a je H ili C1-4 alkil; svaka R4b je, nezavisno, H ili C1-4 alkil; ili dve R4b grupe, zajedno sa atomom ugljenika na koji su vezane, formiraju 3-, 4-, 5-, ili 6- člani prsten cikloalkila; svaka R5 je, nezavisno , halo, cijano, nitro, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halosulfanil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, C1-10 heteroaril-C1-3 alkil, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(=NRe)Rb, C(=NRe)NRcRd, NRcC(=NRe)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, ili S(O)2NRcRd; pri čemu C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; svaka R6 je, nezavisno, halo, cijano, nitro, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halosulfanil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, C1-10 heteroaril-C1-3 alkil, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, ili S(O)2NRc1Rd1; pri čemu navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih Rh grupa; svaka Ra, Rb, Rc, i Rd je, nezavisno, H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, ili C1-10 heteroaril-C1-3 alkil; pri čemu navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil je opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih Rg grupa; ili bilo koja Rc i Rd zajedno sa atomom N na koji su vezane, formiraju 3-, 4-, 5-, 6-, ili 7-članu heterocikloalkil grupu ili heteroaril grupu, svaku opciono supstituisanu sa 1, 2, 3 ili 4 supstituenta nezavisno izabrana od halo, cijano, nitro, hidroksila, C1-6 alkila, C2-6 alkenila, C2-6 alkinila, C3-7 cikloalkila, C1-6 haloalkila, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di-C1-6 alkilamino, tio, C1-6 alkiltio, C1-6 alkilsulfinial, C1-6 alkilsulfonila, karbamila, C1-6 alkilkarbamila, di-C1-6 alkilkarbamila, karboksi, C1-6 alkilkarbonila, i C1-6 alkoksikarbonila; svaka Re je, nezavisno , H, C1-6 alkil, CN, hidroksil, C1-6 alkoksi, C1-6 alkilsulfonil, karboksi, C1-6 alkilkarbonil, aminosulfonil, C1-6 alkilaminosulfonil, di-C1-6 alkilaminosulfonil, karbamil, C1-6 alkilkarbamil, ili di-C1-6 alkilkarbamil; svaka Ra1, Rb1, Rc1, i Rd1 je, nezavisno, H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, ili C1-10 heteroaril-C1-3 alkil; pri čemu navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil je opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih Rg’ grupa; ili bilo koja Rc1 i Rd1 zajedno sa atomom N na koji su vezane, formiraju 3-, 4-, 5-, 6-, ili 7-članu heterocikloalkil grupu ili heteroaril grupu, svaku opciono supstituisanu sa 1, 2, 3 ili 4 supstituenta nezavisno izabrana od halo, cijano, nitro, hidroksila, C1-6 alkila, C2-6 alkenila, C2-6 alkinila, C3-7 cikloalkila, C1-6 haloalkila, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di-C1-6 alkilamino, tio, C1-6 alkiltio, C1-6 alkilsulfinila, C1-6 alkilsulfonila, karbamila, C1-6 alkilkarbamila, di-C1-6alkilkarbamila, karboksi, C1-6 alkilkarbonila, C1-6 alkoksikarbonila, i C1-6 alkilkarbonilamino; svaka Re1 je, nezavisno, H, C1-6 alkil, CN, hidroksil, C1-6alkoksi, C1-6 alkilsulfonil, karboksi, C1-6 alkilkarbonil, aminosulfonil, C1-6 alkilaminosulfonil, di-C1-6 alkilaminosulfonil, karbamil, C1-6 alkilkarbamil, ili di-C1-6 alkilkarbamil; svaka Rg, Rg’, i Rh je, nezavisno, halo, cijano, nitro, hidroksil, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-7 cikloalkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di-C1-6 alkilamino, tio, C1-6 alkiltio, C1-6 alkilsulfinil, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di-C1-6 alkilkarbamil, karboksi, C1-6 alkilkarbonil, C1-6 alkoksikarbonil, ili C1-6 alkilkarbonilamino; i n je 0, 1, 2, 3, ili 4.
3. Jedinjenje prema patentnom zahtevu 1 ili 2, ili njegova farmaceutski prihvatljiva so, pri čemu a) X je N; ili b) X je CR2; ili c) X je C(H), C(F), ili C(CN); ili d) X je CH.
4. Jedinjenje prema bilo kom od patentnih zahteva 1 do 3, ili njegova farmaceutski prihvatljiva so, pri čemu a) Y je N; ili b) Y je CR3; ili c) Y je CH.
5. Jedinjenje prema bilo kom od patentnih zahteva 1 do 4, ili njegova farmaceutski prihvatljiva so, pri čemu Z je cijano.
6. Jedinjenje prema bilo kom od patentnih zahteva 1 do 5, ili njegova farmaceutski prihvatljiva so, pri čemu a) L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili ili b) L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili C(=O)O.
7. Jedinjenje prema bilo kom od patentnih zahteva 1 do 6, ili njegova farmaceutski prihvatljiva so, pri čemu a) n je 0, 1, ili 2; ili b) n je 0.
8. Jedinjenje prema bilo kom od patentnih zahteva od 1 do 7, ili njegova farmaceutski prihvatljiva so, pri čemu a) R1 je C1-4 alkil; ili b) R1 je metil; ili c) dve R1 grupe formiraju dvočlani ugljenikov most.
9. Jedinjenje prema bilo kom od patentnih zahteva od 1 do 8, ili njegova farmaceutski prihvatljiva so, pri čemu a) A je C6-14 aril, koji je opciono supstituisan sa 1, 2, 3, 4, 5, ili 6 nezavisno izabranih R5 grupa; ili b) A je fenil, koji je opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; ili c) A je monociklični C3-9 cikloalkil ili biciklični C3-9 cikloalkil, od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, 5, ili 6 nezavisno izabranih R5 grupa; ili d) A je monociklični C2-10 heterocikloalkil ili biciklični C2-10 heterocikloalkil, od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, 5, ili 6 nezavisno izabranih R5 grupa; ili e) A je monociklični C1-10 heteroaril ili biciklični C1-10 heteroaril, od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, 5, ili 6 nezavisno izabranih R5 grupa; ili f) A je C1-6 alkil; ili g) A je C1-6 alkil, fenil, prsten naftila, monociklični ili biciklični C3-10 cikloalkil, monociklični ili biciklični C2-10 heterocikloalkil, ili monociklični ili biciklični C1-10 heteroaril; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; ili h) A je fenil, prsten naftila, monociklični C3-10 cikloalkil, biciklični C3-10 cikloalkil, monociklični C2-10 heterocikloalkil, biciklični C2-10 heterocikloalkil, monociklični C1-10 heteroaril, ili biciklični C1-10 heteroaril; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; ili i) A je metil, etil, izopropil, fenil, prsten naftila, prsten piridina, prsten pirimidina, prsten tiofena, prsten pirazina, prsten oksazola, prsten izoksazola, prsten imidazola, prsten tazola, prsten furana, prsten pirazola, prsten hinolina, prsten benzotiofena, prsten benzotiazola, prsten benzoimidazola, prsten benzofurana, ciklopropil, ciklopentil, cikloheksil, cikloheptil, prsten indena, prsten tetrahidronaftalena, prsten dihidro-1,4-benzodioksoksin, ili prsten piperidina; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa, kao što je dopušteno valencom; ili j) A je fenil ili prsten piridina; od kojih je svaki opciono supstituisan sa 1, 2, 3, ili 4 nezavisno izabranih R5 grupa; ili k) A je piridin-4-il; koji je opciono supstituisan sa 1, 2, 3, ili 4 nezavisno izabranih R5 grupa.
10. Jedinjenje prema bilo kom od patentnih zahteva 1 do 9, ili njegova farmaceutski prihvatljiva so, pri čemu a) svaka R5 je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, C6-10 aril, C1-10 heteroaril, ORa, SRa, C(O)ORa, NRcRd, NRcC(O)Rb; pr čemu navedeni C1-6 alkil, C1-6 haloalkil, C6-10 aril, i C1-10 heteroaril su svaki opciono supstituisani sa 1, 2, 3, 4, il 5 nezavisno izabranih R6 grupa; ili b) svaka R5 je, nezavisno, hloro, fluoro, bromo, cijano, metil, etil, trifluorometil, hidroksil, metoksi, trifluorometoksi, difluorometoksi, fenoksi, dimetilamino, t-butilkarbonilamino, metoksikarbonil, metiltio, fenil, prsten piridina, prsten tiazola, prsten hinolina, prsten izohinolina, prsten imidazo[1,2-a]pirimidina, prsten benzoksazola, ili prsten oksadiazola; pri čemu fenil, prsten piridina, prsten tiazola, prsten hinolina, prsten izohinolina, prsten imidazo[1,2-a]pirimidina, prsten benzoksazola, i prsten oksadiazola su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; ili c) svaka R5 je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, C6-10 aril, C1-10 heteroaril, ORa, SRa, C(O)ORa, NRcRd, ili NRcC(O)Rb; pri čemu navedeni C1-6 alkil, C1-6 haloalkil, C6-10 aril, i C1-10 heteroaril su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; svaka Ra, Rb, Rc, i Rd je, nezavisno, H, C1-6 alkil, C1-6 haloalkil, ili C6-10 aril; pri čemu je navedeni C1-6 alkil i C6-10 aril opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih Rg grupa; svaka R6 je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, ORa1, NRc1Rd1, ili OC(O)Rb1; i svaka Ra1, Rb1, Rc1, i Rd1 je, nezavisno, H ili C1-6 alkil; pri čemu je navedeni C1-6 alkil opciono supstituisan sa supstituentom nezavisno izabranim od C1-4 alkoksi i hidroksila; ili bilo koja Rc1 i Rd1 zajedno sa atomom N na koji su vezane, formiraju 4-, 5-, 6-, ili 7-članu heterocikloalkil grupu, opciono supstituisano sa 1, 2, 3 ili 4 supstituenata nezavisno izabranih od halo; ili d) svaka R5 je, nezavisno, halo ili C1-6 haloalkil; ili e) svaka R5 je, nezavisno, fluoro ili trifluorometil.
11. Jedinjenje prema bilo kom od patentnih zahteva 1 do 4 i 9 do 10, koje ima a) Formulu (II): ili njegovu farmaceutski prihvatljivu so; ili b) Formulu (III): ili njegovu farmaceutski prihvatljivu so.
12. Jedinjenje prema patentnom zahtevu 1 ili 2, ili njegova farmaceutski prihvatljiva so, pri čemu: a) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno, C1-4 alkil; ili dve R1 grupe formiraju dvočlani ugljenikov most; R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili A je C1-6 alkil, fenil, prsten naftila, monociklični C3-10 cikloalkil, biciklični C3-10 cikloalkil, monociklični C2-10 heterocikloalkil, biciklični C2-10 heterocikloalkil, monociklični C1-10 heteroaril, ili biciklični C1-10 heteroaril; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; svaka R5 je,nezavisno , halo, cijano, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, C1-10 heteroaril-C1-3 alkil, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, ili S(O)2NRcRd; pri čemu C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, C3-10 cikloalkil-C1-3 alkil, C2-10 heterocikloalkil, C2-10 heterocikloalkil-C1-3 alkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, i C1-10 heteroaril-C1-3 alkil su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 ezavisno izabranih R6 grupa; i n je 0, 1, ili 2; ili b) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno, C1-4 alkil; ili dve R1 grupe formiraju dvočlani ugljenikov most. R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili A je C1-6 alkil, fenil, prsten naftila, monociklični C3-10 cikloalkil, biciklični C3-10 cikloalkil, monociklični C2-10 heterocikloalkil, biciklični C2-10 heterocikloalkil, monociklični C1-10 heteroaril, ili biciklični C1-10 heteroaril; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; svaka R5 je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, C3-10 cikloalkil, C2-10 heterocikloalkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)2Rb, ili S(O)2NRcRd; pri čemu C1-6 alkil, C1-6 haloalkil, C3-10 cikloalkil, C2-10 heterocikloalkil, C6-10 aril, C6-10 aril-C1-3 alkil, i C1-10 heteroaril su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; i n je 0, 1, ili 2; ili c) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno, C1-4 alkil; ili dve R1 grupe formiraju dvočlani ugljenikov most. R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili A je fenil, prsten naftila, monociklični C3-10 cikloalkil, biciklični C3-10 cikloalkil, monociklični C2-10 heterocikloalkil, biciklični C2-10 heterocikloalkil, monociklični C1-10 heteroaril, ili biciklični C1-10 heteroaril; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; svaka R5je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, C3-10 cikloalkil, C2-10 heterocikloalkil, C6-10 aril, C6-10 aril-C1-3 alkil, C1-10 heteroaril, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)2Rb, ili S(O)2NRcRd; pri čemu C1-6 alkil, C1-6 haloalkil, C3-10 cikloalkil, C2-10 heterocikloalkil, C6-10 aril, C6-10 aril-C1-3 alkil, i C1-10 heteroaril su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; i n je 0, 1, ili 2; ili d) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno , C1-4 alkil; ili dve R1 grupe formiraju dvočlani ugljenikov most. R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili A je C1-6 alkil, fenil, prsten naftila, monociklični C3-10 cikloalkil, biciklični C3-10 cikloalkil, monociklični C2-10 heterocikloalkil, biciklični C2-10 heterocikloalkil, monociklični C1-10 heteroaril, ili biciklični C1-10 heteroaril; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; svaka R5 je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, C6-10 aril, C1-10 heteroaril, ORa, SRa, C(O)ORa, NRcRd, NRcC(O)Rb; pri čemu navedeni C1-6 alkil, C1-6 haloalkil, C6-10 aril, i C1-10 heteroaril su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; i n je 0, 1, ili 2; ili e) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno, C1-4 alkil; ili dve R1 grupe formiraju dvočlani ugljenikov most. R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili A je fenil, prsten naftila, monociklični C3-10 cikloalkil, biciklični C3-10 cikloalkil, monociklični C2-10 heterocikloalkil, biciklični C2-10 heterocikloalkil, monociklični C1-10 heteroaril, ili biciklični C1-10 heteroaril; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; svaka R5 je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, C6-10 aril, C1-10 heteroaril, ORa, SRa, C(O)ORa, NRcRd, NRcC(O)Rb; pri čemu navedeni C1-6 alkil, C1-6 haloalkil, C6-10 aril, i C1-10 heteroaril su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; i n je 0, 1, ili 2; ili f) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno, metil; ili dve R1 grupe formiraju dvočlani ugljenikov most. R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili A je metil, etil, izopropil, fenil, prsten naftalena, prsten piridina, prsten pirimidina, prsten tiofena, prsten pirazina, prsten oksazola, prsten izoksazola, prsten imidazola, prsten tiazola, prsten furana, prsten pirazola, prsten hinolina, prsten benzotiofena, prsten benzotiazola, prsten benzoimidazola, prsten benzofurana, ciklopropil, ciklopentil, cikloheksil, cikloheptil, prsten indena, prsten tetrahidronaftalena, prsten dihidro-1,4-benzodioksoksin, ili prsten piperidina; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, 5,ili 6 nezavisno izabranih R5 grupa, kao što je dozvoljeno valencom; svaka R5 je, nezavisno, hloro, fluoro, bromo, cijano, metil, etil, trifluorometil, hidroksil, metoksi, trifluorometoksi, difluorometoksi, fenoksi, dimetilamino, t-butilkarbonilamino, metoksikarbonil, metiltio, fenil, prsten piridina, prsten tiazola, prsten hinolina, prsten izohinolina, prsten imidazo[1,2-a]pirimidina, prsten benzoksazola, ili prsten oksadiazola; pri čemu navedeni fenil, prsten piridina, prsten tiazola, prsten hinolina, prsten izohinolina, prsten imidazo[1,2-a]pirimidina, prsten benzoksazola, i prsten oksadiazola su svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; i n je 0, 1, ili 2; ili g) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno, metil; ili dve R1 grupe formiraju dvočlani ugljenikov most. R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, ili A je fenil, prsten naftalena, prsten piridina, prsten pirimidina, prsten tiofena, prsten pirazina, prsten oksazola, prsten izoksazola, prsten imidazola, prsten tiazola, prsten furana, prsten pirazola, prsten hinolina, prsten benzotiofena, prsten benzotiazola, prsten benzoimidazola, prsten benzofurana, ciklopropil, ciklopentil, cikloheksil, cikloheptil, prsten indena, prsten tetrahidronaftalena, prsten dihidro-1,4-benzodioksoksin, ili prsten piperidina; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, 5, ili 6 nezavisno izabranih R5 grupa; svaka R5 je, i nezavisno, hloro, fluoro, bromo, cijano, metil, etil, trifluorometil, hidroksil, metoksi, trifluorometoksi, difluorometoksi, fenoksi, dimetilamino, t-butilkarbonilamino, metoksikarbonil, metiltio, fenil, prsten piridina, prsten tiazola, prsten hinolina, prsten izohinolina, prsten imidazo[1,2-a]pirimidina, prsten benzoksazola, prsten oksadiazola; pri čemu navedeni fenil, prsten piridina, prsten tiazola, prsten hinolina, prsten izohinolina, prsten imidazo[1,2-a]pirimidina, prsten benzoksazola, i prsten oksadiazola su svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; i n je 0, 1, ili 2; ili h) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno , C1-4 alkil; ili dve R1 grupe formiraju dvočlani ugljenikov most. R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je S(=O)2; A je C1-6 alkil; i n je 0, 1, ili 2; ili i) X je N ili CH; Y je N; Z je cijano; L je C(=O) ili C(=O)NH; A je fenil ili prsten piridina, od kojih je svaki opciono supstituisan sa 1, 2, 3, ili 4 nezavisno izabranih R5 grupa; svaka R5 je, nezavisno, halo ili C1-6 haloalkil; i n je 0; ili j) X je N ili CH; Y je N; Z je cijano; L je C(=O) ili C(=O)NH; A je fenil ili piridin-4-il, od kojih je svaki opciono supstituisan sa 1 ili 2 nezavisno izabrane R5 grupe; svaka R5 je, nezavisno , fluoro ili trifluorometil; i n je 0; ili k) X je N ili CR2; Y je N ili CR3; svaka R1 je, nezavisno, C1-4 alkil, hidroksil, C1-4 alkoksi, ili fluoro; dve R1 grupe zajedno formiraju dvočlani ili tročlani ugljenikov most ili most od formule -CH2-O-CH2-; R2 je H, halo, ili cijano; R3 je H; Z je cijano; L je C(=O)NH, C(=O), S(=O)2, CH2, C(=O)CH2, C(=O)O, ili C(=O)OCH2; A je C1-6 alkil, fenil, prsten naftila, monociklični C3-10 cikloalkil, biciklični C3-10 cikloalkil, monociklični C2-10 heterocikloalkil, biciklični C2-10 heterocikloalkil, monociklični C1-10 heteroaril, ili biciklični C1-10 heteroaril; od kojih je svaki opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih R5 grupa; svaka R5 je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, C6-10 aril, C1-10 heteroaril, ORa, SRa, C(O)ORa, NRcRd, NRcC(O)Rb; pri čemu navedeni C1-6 alkil, C1-6 haloalkil, C6-10 aril, i C1-10 heteroaril su svaki opciono supstituisani sa 1, 2, 3, 4, ili 5 nezavisno izabranih R6 grupa; n je 0, 1, ili 2; svaka Ra, Rb, Rc, i Rd je, nezavisno, H, C1-6 alkil, C1-6 haloalkil, ili C6-10 aril; pri čemu navedeni C1-6 alkili C6-10 aril je opciono supstituisan sa 1, 2, 3, 4, ili 5 nezavisno izabranih Rg grupa; svaka R6 je, nezavisno, halo, cijano, C1-6 alkil, C1-6 haloalkil, ORa1, NRc1Ra1, ili OC(O)Rb1; i svaka Ra1, Rb1, Rc1, i Rd1 je, nezavisno, H ili C1-6 alkil; pri čemu navedeni C1-6 alkil je opciono supstituisan sa supstituentom nezavisno izabranim od C1-4 alkoksi ili hidroksila; ili bilo koja Rc1 i Rd1 zajedno sa atomom N na koji su vezane, formiraju 4-, 5-, 6-, ili 7-članu heterocikloalkil grupu, opciono supstituisani sa 1, 2, 3 ili 4 supstituenata nezavisno izabrana od halo.
13. Jedinjenje prema patentnom zahtevu 1, pri čemu a) Jedinjenje je izabrano od: {1-{1-[3-fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il} -3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il} acetonitrila; {1-[1-(3-fluoro-4-hinolin-6-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3,5-difluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(3,4,5-trifluorobenzoil)piperidin-4-il]azetidin- 3-il} acetonitrila; {1-[1-(3-fluoro-4-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-hidroksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[2-fluoro-3-(trifluorometil)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(cikloheksilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-(1-benzoilpiperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; 2-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]benzonitrila; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]benzonitrila; 4-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]benzonitrila; {1-{1-[(6-hloropiridin-2-il)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(pirazin-2-ilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- l} acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(3-tienilkarbonil)piperidin-4-il]azetidin-3- il}acetonitrila; {1-[1-(1,3-oksazol-2-ilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo [2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-(1-{[2-metil-5-(trifluorometil)-1,3-oksazol-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin- 4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-5-fluorobenzonitrila; {1-[1-(3-hlorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(3-bromobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; (3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-{1-[3-(trifluorometoksi)benzoil]piperidin-4- il}azetidin-3-il)acetonitrila; (3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-{1-[3-(trifluorometil)benzoil]piperidin-4-il}azetidin- 3-il)acetonitrila; {1-{1-[3-fluoro-5-(trifluorometil)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il] azetidin-3-il}acetonitrila; {1-[1-(3,5-dihlorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(3-fluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(4-fluoro-3-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(2-fluoro-5-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3-hloro-5-fluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(3-bromo-5-fluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-{1-[(2,5-dihloro-3-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(2,4,5-trifluoro-3-metoksibenzoil)piperidin-4- il]azetidin-3-il}acetonitrila; {1-[1-(3,5-dimetoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(3-hloro-4-fluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(3,4-difluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(3-fluoro-5-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il] azetidin-3-il}acetonitrila; {1-[1-(2-hloro-6-metoksiizonikotinoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(5-fluoro-2-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(2-fluoro-6-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(4-fluoro-2-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(2,3-difluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(2,4-difluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il])-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(2,5-difluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(2,6-difluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-{1-[2-fluoro-6-(trifluorometil)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(2,3,4-trifluorobenzoil)piperidin-4-il]azetidin- 3-il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(2,3,6-trifluorobenzoil)piperidin-4-il]azetidin- 3-il} acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(2,4,5-trifluorobenzoil)piperidin-4-il]azetidin- 3-il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(2,4,6-trifluorobenzoil)piperidin-4-il]azetidin- 3-il}acetonitrila; {1-[1-(3,5-dibromo-4-metoksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-6-(dimetilamino)-2-fluorobenzonitrila; {1-{1-[3-fluoro-4-(trifluorometil)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-(1-{[4-hloro-6-(trifluorometil)piridin-2-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4- il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(2,3,4,5-tetrafluorobenzoil)piperidin-4-il]azetidin-3-il}acetonitrila; 5-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-2-metoksibenzonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(2,3,5,6-tetrafluorobenzoil)piperidin-4-il]azetidin-3-il}acetonitrila; (3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-{1-[2-(trifluorometil)izonikotinoil]piperidin-4- il}azetidin-3-il)acetonitrila; {1-[1-(4-fluoro-3-hidroksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 5-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-2-(dimetilamino)benzonitrila; {1-{1-[4-(dimetilamino)-2,3,5,6-tetrafluorobenzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)- 1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-[1-(3,5-difluoroizonikotinoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-{1-[3-fluoro-4-(metiltio)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(4-hloro-3-fluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(3-fluoro-4-metilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(2,5-dimetil-3-furoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; 4-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-2-fluorobenzonitrila; {1-[1-(2-fluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il} acetonitrila; {1-[1-(4-fluorobenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il} acetonitrila; {1-[1-(2-tienilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-{1-[3-metoksi-5-(trifluorometil)-2-tienilkarbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4- il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-1-[3-hidroksi-5-(trifluorometil)-2-tienilkarbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)- 1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{1-[(4-metoksi-3-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(5-metil-3-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(5-hloro-4-metoksi-3-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[(2-bromo-3-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo [2,3-d]pirimidin-4-il)-1H-pirazol-1-il] azetidin-3-il}acetonitrila; {1-{1-[(3-hloro-2-tienil)karbonil]piperidin-4-il}-3-3-[4-(7H-pirolo [2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(5-hloro-2-tienil)karbonil]piperidin-4-il}-3-3-[4-(7H-pirolo [2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{-[(3-metil-2-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(4-metil-2-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(5-metil-2-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(3-metoksi-2-tienil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[2-fluoro-4-(trifluorometil)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; 4-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-3,5-difluorobenzonitrila; {1-[1-(3-hloro-4-hidroksibenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; [3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-(1-{[2-(trifluorometil)pirimidin-4-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; [3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-(1-{[6-(trifluorometil)pirazin-2-il]karbonil}piperidin- 4-il)azetidin-3-il]acetonitrila; {1-[1-(1-naftoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(hinolin-3-ilkarbonil)piperidin-4-il]azetidin- 3-il} acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(hinolin-6-ilkarbonil)piperidin-4-il]azetidin- 3-il} acetonitrila; {1-[1-(1-benzotien-2-ilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(3-hloro-6-fluoro-1-benzotien-2-il)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)- 1H-pirazol-1-il]azetidin-3-il{ acetonitrila; {1-{1-[(3-hloro-4-fluoro-1-benzotien-2-il)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)- 1H-pirazol-1-il]azetidin-3-il}acetonitrila; [3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-(1-{[4-(trifluorometil)-1-benzotien-2-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; [3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-(1-{[6-(trifluorometil)-1-benzotien-2-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; [3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-(1-{[7-(trifluorometil)-1-benzotien-2-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; {1-[1-(1-benzotien-3-ilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[1-(1,2,3,4-tetrahidronaftalen-2-ilkarbonil) piperidin-4-il]azetidin-3-il}acetonitrila; [3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-(1-{[4-(trifluorometil)cikloheksil]karbonil}piperidin-4-il)azetidin-3-il]acetonitrila; {1-[1-(2,3-dihidro-1H-inden-2-ilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[(4,4-difluorocikloheksil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(ciklopentilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(cikloheptilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-{1-[(3-metoksicikloheksil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(4-fenilcikloheksil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-(1-{[4-(4-hlorofenil)cikloheksil]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; 6-{4-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]piperidin-1-il}nikotinonitrila; {1-(1-{[[1-(5-hloro-3-fluoropiridin-2-il)piperidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; 2-{4-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]piperidin-1-il}-6-metilnikotinonitrila; {1-[1-(fenilacetil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{1-[(1-fenilciklopropil)karbonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-(1-{[1-(4-hlorofenil)ciklopropil]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[(2,6-dihlorofenil)acetil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(mezitilacetil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-[1-(bifenil-4-ilkarbonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(3-fluoro-4-izohinolin-6-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(2,6-difluoro-4-piridin-3-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-piridin-4-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 4’-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-2’-fluorobifenil-4-karbonitrila; 4’-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-2’,3-difluorobifenil-4-karbonitrila; {1-[1-(2-fluoro-4-piridin-3-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[4-fluoro-3-(1,3-tiazol-2-il)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[3-fluoro-4-(1,3-tiazol-2-il)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-piridin-3-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 4’-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-2’-fluorobifenil-2-karbonitrila; 4’-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-2’-fluorobifenil-3-karbonitrila; 4’-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]bifenil-4-karbonitrila; (3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-{1-[(2,3’,4’-trifluorobifenil-4-il)karbonil]piperidin- 4-il}azetidin-3-il)acetonitrila; 4’-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-2’,5-difluorobifenil-3-karbonitrila; {1-[1-(3-fluoro-4-hinolin-5-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-izohinolin-5-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-izohinolin-8-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-hinolin-8-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-izohinolin-7-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-hinolin-7-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-imidazo[1,2-a]piridin-6-ilbenzoil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)- 1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{1-[4-(1,3-benzoksazo1-2-il)benzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[4-(1,3-benzoksazol-2-il)-3-fluorobenzoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; 3-[(3-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-8-azabiciklo[ 3.2.1]okt-8-il)karbonil]-5-fluorobenzonitrila; {1-[8-(3,4-difluorobenzoil)-8-azabiciklo[3.2.1]okt-3-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; 4-[(3-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-8-azabiciklo[ 3.2.1]okt-8-il)karbonil]-2-fluorobenzonitrila; {1-[8-(4-hloro-3-fluorobenzoil)-8-azabiciklo[3.2.1]okt-3-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{8-[3-fluoro-2-(trifluorometil)izonikotinoil]-8-azabiciklo[3.2.1]okt-3-il{-3-[4-(7H-pirolo[2,3-d]pirimidin- 4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; [3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-(8-{[6-(trifluorometil)piridin-3-il]karbonil}-8- azabiciklo[3.2.1]okt-3-il)azetidin-3-il]acetonitrila; (3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-{8-[2-(trifluorometil)izonikotinoil]-8-azabiciklo[ 3.2.1]okt-3-il}azetidin-3-il)acetonitrila; {1-[8-(ciklopentilkarbonil)-8-azabiciklo[3.2.1]okt-3-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-[8-(tetrahidro-2H-piran-4-ilkarbonil)-8-azabiciklo[ 3.2.1]okt-3-il]azetidin-3-il}acetonitrila; {1-[8-(cikloheksilkarbonil)-8-azabiciklo[3.2.1]okt-3-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{8-[(4,4-difluorocikloheksil)karbonil]-8-azabiciklo[3.2.1]okt-3-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)- 1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-[1-(3-fluorobenzoil)-2-metilpiperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(3-fluorobenzoil)-2-metilpiperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-1-[(4,4-difluorocikloheksil)karbonil]-2-metilpiperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-[1-(3-fluorobenzoil)-4-metilpiperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(cikloheksilkarbonil)-4-metilpiperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-fluoro-2-(trifluorometil)fenil]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[3-(trifluorometil) piridin-4-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,6-difluorofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[2-(trifluorometil) fenil]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[2-(trifluorometoksi) fenil]piperidin-1-karboksamida; N-(4-bromo-3-tienil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 1-il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,6-dihlorofenil) piperidin-1-karboksamida; N-(2-hloro-6-metilfenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1-karboksamida; N-(2-hloro-4-fluorofenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1-karboksamida; N-(2-hlorofenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[2-(difluorometoksi) fenil]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-(trifluorometil) piridin-3-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[3-(trifluorometil) fenil]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-(trifluorometil) fenil]piperidin-1-karboksamida; N-(5-hloro-2-metilfenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2-fluorofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[2-fluoro-3-(trifluorometil)fenil]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,4-difluorofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,3,4-trifluorofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,3,5-trifluorofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,5-difluorofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(3,5-difluorofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(3,4-difluorofenil) piperidin-1-karboksamida; N-(3-hloro-2-fluorofenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1-karboksamida; N-(4-hloro-2-fluorofenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-3-tienilpiperidin- 1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2-metoksifenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(3-metoksifenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-(trifluorometoksi) fenil]piperidin-1-karboksamida; N-(3-hlorofenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksamida; N-(4-hlorofenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2-metilfenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,5-dimetoksifenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(4-fluoro-2- metilfenil)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[6-(trifluorometil) piridin-2-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,6-dimetilpiridin- 3-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-1,3-tiazol-2-il-piperidin-1-karboksamid; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(4-metil-1,3- tiazol-2-il)piperidin-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(4,5-dimetil- 1,3-tiazol-2-il)piperidin-1-karboksamida; N-1,3-benzotiazol-2-il-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 1-il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(1-metil-1H-benzimidazol-2-il)piperidin-1-karboksamid; N-[4-(4-hlorofenil)-1,3-tiazol-2-il]-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-1-il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(-etil-1H-pirazol- 5-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(1,3-dimetil- 1H-pirazol-5-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2-metilpiridin- 3-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(6-fluoro-2- metilpiridin-3-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2-fluoro-6- metilpiridin-3-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[3-(trifluorometil) piridin-2-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(3-fluoropiridin- 2-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(3,5-difluoropiridin- 2-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2-metoksipiridin- 3-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[2-metil-6-(trifluorometil)piridin-3-il]piperidin-1-karboksamida; metil 2-{[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]aminobenzoata; metil 2-{[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]amino}-5-fluorobenzoata; metil 4-{[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]amino}-3-fluorobenzoata; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)metil]-6-(dimetilamino)-2-fluorobenzonitrila; {1-[1-(3,5-dihlorobenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-1-[2-hloro-5-(trifluorometil)benzil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[2-fluoro-3-(trifluorometil)benzil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[2-fluoro-6-(trifluorometil)benzil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[(2-hlorohinolin-3-il)metil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3,5-difluorobenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-{1-[2-fluoro-4-(trifluorometil)benzil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(2,4-difluorobenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(2-fluoro-6-metoksibenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(2,3-dihlorobenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; 5-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)metil]-2-fluorobenzonitrila; {1-{1-[4-(1,2,3-oksadiazol-4-il)benzil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 2-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)metil]benzonitrila; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)metil]benzonitrila; 6-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)metil]-2-metoksinikotinonitrila; {1-{1-[(2,6-dibromopiridin-4-il)metil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{-[(2-bromopiridin-4-il)metil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(2-hloro-6-fluorobenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(3-hloro-2,6-difluorobenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 4-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)metil]-2-fluorobenzonitrila; {1-{1-[(5-metil-3-fenilizoksazol-4-il)metil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-(1-{[3-fluoro-2-(trifluorometil)piridin-4-il]metil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)- 1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-[1-(1-benzofuran-2-ilmetil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(3-fenoksibenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(2,3-dihidro-1,4-benzodiksin-6-ilmetil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; N-{4-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)metil]piridin-2-il}-2,2-dimetilpropanamida; {1-{11-[3-hloro-2-fluoro-6-(trifluorometil)benzil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)- 1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{1-[(3,5-dihloropiridin-4-il)metil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{-[(2-hloro-6-metoksihinolin-3-il)metil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(2-hloro-3,4-dimetoksibenzil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 3-[(3-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-8-azabiciklo[ 3.2.1]okt-8-il)metil]-6-(dimetilamino)-2-fluorobenzonitrila; {1-[8-(2-hloro-3,6-difluorobenzil)-8-azabiciklo[3.2.1]okt-3-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-2-metilpiperidin- 1-il)metil]-6-(dimetilamino)-2-fluorobenzonitrila; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-2-metilpiperidin- 1-il)metil]-6-(dimetilamino)-2-fluorobenzonitrila; {1-[1-(2-hloro-6-fluorobenzil)-2-metilpiperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(2-hloro-6-fluorobenzil)-2-metilpiperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-{1-[(1-metil-1H-pirazol-5-il)sulfonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; 2-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)sulfonil]benzonitrila; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)sulfonil]benzonitrila; 4-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)sulfonil]benzonitrila; 5-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)sulfonil]-2-(dimetilamino)benzonitrila; {1-{1-[(1-metil-1H-pirazol-3-il)sulfonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(cikloheksilsulfonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(ciklopentilsulfonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(metilsulfonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(etilsulfonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-[1-(ciklopropilsulfonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-[1-(izopropilsulfonil)piperidin-4-il]-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3- il}acetonitrila; {1-{-[(1-metil-1H-imidazol-4-il)sulfonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[(1,2-dimetil-1H-imidazol-4-il)sulfonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[(3,5-dimetilizoksazol-4-il)sulfonil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[3-fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol- 1-il]azetidin-3-il}acetonitrila; 3-[(4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}piperidin-1- il)karbonil]benzonitrila; 3-[(4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-5-fluorobenzonitrile; 4-[(4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-3-fluorobenzonitrila; 4-[(4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-3,5-difluorobenzonitrila; {1-{1-[5-fluoro-2-(trifluorometil)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1- il]azetidin-3-il}acetonitrila; {1-{1-[3-fluoro-4-(trifluorometil)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1- il]azetidin-3-il}acetonitrila; (3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]-1-{1-[3-(trifluorometil)benzoil]piperidin-4-il}azetidin- 3-il)acetonitrila; {1-{1-[2-fluoro-5-(trifluorometoksi)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol- 1-il]azetidin-3-il}acetonitrila; {3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]-1-[1-(2,3,6-trifluorobenzoil)piperidin-4-il]azetidin-3- il}acetonitrila; {3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]-1-[1-(2-tienilkarbonil)piperidin-4-il]azetidin-3- il}acetonitrila; {1-{1-[2-fluoro-4-(trifluorometil)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1- il]azetidin-3-il}acetonitrila; {1-{1-[2-fluoro-5-(trifluorometil)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1- il]azetidin-3-il}acetonitrila; {1-{1-[3-fluoro-5-(trifluorometil)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1- il]azetidin-3-il}acetonitrila; {1-{1-[4-fluoro-3-(trifluorometil)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1- il]azetidin-3-il}acetonitrila; {1-[1-(2,3-difluorobenzoil)piperidin-4-il]-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-3- il}acetonitrila; {1-[1-(3,4-difluorobenzoil)piperidin-4-il]-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-3- il}acetonitrila; {1-[1-(2,5-difluorobenzoil)piperidin-4-il]-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-3- il}acetonitrila; {1-[1-(2,6-difluorobenzoil)piperidin-4-il]-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-3- il}acetonitrila; {3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]-1-[1-(2,3,4-trifluorobenzoil)piperidin-4-il]azetidin-3- il}acetonitrila; {1-{1-[2-fluoro-3-(trifluorometoksi)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[4-hidroksi-3-(trifluorometil)benzoil]piperidin-4-il}-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol- 1-il]azetidin-3-il}acetonitrila; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-[4-fluoro-2-(trifluorometil)fenil]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-(2-metoksipiridin- 3-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-[2-metil-6-(trifluorometil)piridin-3-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-(2,4-difluorofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-(2-cijanofenil) piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-(2-metoksifenil) piperidin-1-karboksamida; N-(2-hloro-4-fluorofenil)-4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin- 1-il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-[3-(trifluorometil) piridin-2-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-[4-(trifluorometil) piridin-3-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-1-il}-N-(3-fluoropiridin- 2-il)piperidin-1-karboksamida; N-(4-hloro-2-cijanofenil)-4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1-karboksamida; {1-{1-[3-fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; 4-[(4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1-il)karbonil]-3-fluorobenzonitrila; {1-[1-(3-fluoro-4-hidroksibenzoil)piperidin-4-il]-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-[1-(2-fluoro-4-hidroksibenzoil)piperidin-4-il]-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin- 3-il}acetonitrila; {1-{1-[5-hloro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; [3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-(1{[2-(trifluorometil)pirimidin-4-il]karbonil}piperidin- 4-il)azetidin-3-il]acetonitrila; [3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-(1{[6-(trifluorometil)pirazin-2-il]karbonil}piperidin- 4-il)azetidin-3-il]acetonitrila; [3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-(1{[5-(trifluorometil)pirazin-2-il]karbonil}piperidin- 4-il)azetidin-3-il]acetonitrila; {1-{{1-[(4,4-difluorocikloheksil)karbonil]piperidin-4-il}-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-fluoro-2-(trifluorometil)fenil]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2,4-difluorofenil) piperidin-1-karboksamida; N-(2-hloro-4-fluorofenil)-4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin- 1-il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2-metoksipiridin- 3-il)piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[3-(trifluorometil) piridin-4-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-(trifluorometil) piridin-3-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-(2-fluorofenil) piperidin-1-karboksamida; N-(2-hlorofenil)-4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-cijano-2-(trifluorometil)fenil]piperidin-1-karboksamida; N-(4-cijano-2-fluorofenil)-4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin- 1-il}piperidin-1-karboksamida; N-(2-hloro-4-cijanofenil)-4-{3-(cijanometil)-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin- 1-il}piperidin-1-karboksamida; (3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-{1-[3-fluoro-2-(trifluorometil)izonikotinoil] piperidin-4-il}azetidin-3-il)acetonitrila; 5-[(4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]izoftalonitrila; 3-[(4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]-5-fluorobenzonitrila; 4-[(4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]-3-fluorobenzonitrila; 5-[(4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]-2-fluorobenzonitrila; {1-{1-[(5-fluoropiridin-2-il)karbonil]piperidin-4-il}-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoroizonikotinoil)piperidin-4-il]-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3,5-difluoroizonikotinoil)piperidin-4-il]-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(3-fluoro-4-hidroksibenzoil)piperidin-4-il]-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; {1-[1-(2-fluoro-4-hidroksibenzoil)piperidin-4-il]-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1- il]azetidin-3-il}acetonitrila; 2-[(4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]terftalonitrila; 4-[(4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]-2-fluorobenzonitrila; {1-{1-[5-hloro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)- 1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{11-[(4,4-difluorocikloheksil)karbonil]piperidin-4-il}-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; 4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-fluoro- 2-(trifluorometil)fenil]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[3-(trifluorometil)piridin-2-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[4-(trifluorometil)piridin-3-il]piperidin-1-karboksamida; 4-{3-(cijanometil)-3-[4-(5-fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-[3-(trifluorometil)piridin-4-il]piperidin-1-karboksamida; 4-[1-(3-(cijanometil)-1-{1-[3-fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}azetidin-3-il)-1H-pirazol- 4-il]-1H-pirolo[2,3-b]piridine-5-karbonitrila; 4-{1-[1-[1-(3-cijano-5-fluorobenzoil)piperidin-4-il]-3-(cijanometil)azetidin-3-il]-1H-pirazol-4-il}-1H-pirolo[ 2,3-b]piridine-5-karbonitrila; 4-{1-[1-[1-(4-cijano-3-fluorobenzoil)piperidin-4-il]-3-(cijanometil)azetidin-3-il]-1H-pirazol-4-il}-1H-pirolo[ 2,3-b]piridine-5-karbonitrila; 4-(1-{3-(cijanometil)-1-[1-(2,5-dibromobenzoil)piperidin-4-il]azetidin-3-il}-1H-pirazol-4-il)-1H-pirolo[ 2,3-b]piridin-5-karbonitrila; 4-(1-{3-(cijanometil)-1-[1-(3,5-dibromobenzoil)piperidin-4-il]azetidin-3-il}-1H-pirazol-4-il)-1H-pirolo[ 2,3-b]piridin-5-karbonitrila; 2-[(4-{3-(cijanometil)-3-[4-(5-cijano-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]terftalonitrila; 5-[(4-{3-(cijanometil)-3-[4-(5-cijano-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-il)karbonil]izoftalonitrila; 4-{1-[1-[1-(4-cijano-2-fluorobenzoil)piperidin-4-il]-3-(cijanometil)azetidin-3-il]-1H-pirazol-4-il}-1H-pirolo[ 2,3-b]piridin-5-karbonitrila; 4-{1-[1-[1-(4-cijano-2,6-difluorobenzoil)piperidin-4-il]-3-(cijanometil)azetidin-3-il]-1H-pirazol-4-il}-1H-pirolo[2,3-b]piridin-5-karbonitrila; 4-{1-[1-{1-[5-hloro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-(cijanometil)azetidin-3-il]-1H-pirazol- 4-il}-1H-pirolo[2,3-b]piridin-5-karbonitrila; {1-{1-[5-Hloro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol- 1-il]azetidin-3-il}acetonitrila; {1-{1-[5-Fluoro-2-(trifluorometil)izonikotinoil]pipendin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; [3-[4-(7H-Pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]-1-(1-{[4-(trifluorometil)-1,3-tiazol-2-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; [3-[3-(7H-Pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]-1-(1-{[2-(trifluorometil)pirimidin-4-il]karbonil}piperidin- 4-il)azetidin-3-il]acetonitrila; [3-[3-(7H-Pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]-1-(1-{[4-(trifluorometil)-1,3-tiazol-2-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; [3-[3-(7H-Pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]-1-(1-{[5-(trifluorometil)pirazin-2-il]karbonil}piperidin- 4-il)azetidin-3-il]acetonitrila; {1-[1-(Metilsulfonil)piperidin-4-il]-3-[3-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirol-1-il]azetidin-3-il}acetonitrila; [3-[4-(1H-Pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-(1-{[5-(trifluorometil)pirazin-2-il]karbonil}piperidin- 4-il)azetidin-3-il]acetonitrila; [3-[4-(1H-Pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-(1-{[4-(trifluorometil)-1,3-tiazol-2-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; {1-[1-(Metilsulfonil)piperidin-4-il]-3-[4-(1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; [3-[4-(5-Fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-(1-{[6-(trifluorometil)pirazin-2-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; [3-[4-(5-Fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-(1-{[2-(trifluorometil)pirimidin-4-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; [3-[4-(5-Fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-(1-{[5-(trifluorometil)pirazin-2-il]karbonil} piperidin-4-il)azetidin-3-il]acetonitrila; {3-[4-(5-Fluoro-1H-pirolo[2,3-b]piridin-4-il)-1H-pirazol-1-il]-1-[1-(metilsulfonil)piperidin-4-il]azetidin- 3-il}acetonitrila; 4-[1-(3-(Cijanometil)-1-{1-[5-fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}azetidin-3-il)-1H-pirazol- 4-il]-1H-pirolo[2,3-b]piridin-5-karbonitrila; i 4-(1-{3-(Cijanometil)-1-[1-(metilsulfonil)piperidin-4-il]azetidin-3-il}-1H-pirazol-4-il)-1H-pirolo[2,3- b]piridine-5-karbonitrila; ili farmaceutski prihvatljive soli bilo kojeg od gore navedenih; ili b)jedinjenje je izabrano od: cis-{1-{(3-Metoksi-1-[3-fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin- 4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(cis-3-Metoksi-1-{[2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{cis-3-Fluoro-1-[3-fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin- 4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(cis-3-Fluoro-1-{[2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin- 4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{1-[3-Fluoro-2-(trifluorometil)izonikotinoil]-4-deuteropiperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin- 4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{1-[3-Fluoro-2-(trifluorometil)izonikotinoil]3,3,4,5,5-pentadeuteropiperidin-4-il{-3-[4-(7H-pirolo[2,3- d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-{7-[3-Fluoro-2-(trifluorometil)izonikotinoil]-3-oksa-7-azabiciklo[3.3.1]non-9-il}-3-[4-(7H-pirolo[2,3- d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[4-[(dimetilamino)metil]-6-(trifluorometil)piridin-2-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}-N-izopropilpiperidin- 1-karboksamida; {1-1-[6-[(dimetilamino)metil]-3-fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; 3-[(4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- il)karbonil]-5-[(dimetilamino)metil]benzonitrila; {1-(1-{[6-[(dimetilamino)metil]-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-[(metilamino)metil]-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-(azetidin-1-ilmetil)-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-[(dietilamino)metil]-2-(trifluorometil)pirimidin-4-il]karbonil{piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-{[etil(metil)amino]metil}-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{3-(difluorometil)-5-[(dimetilamino)metil]benzoil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin- 4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-(pirolidin-1-ilmetil)-2-(trifluorometil)pirimidin-4-il] karbonil}piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-{[(3S)-3-fluoropirolidin-1-il]metil}-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)- 3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-{[(3R)-3-fluoropirolidin-1-il]metil}-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)- 3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-[(3,3-difluoropirolidin-1-il)metil]-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)- 3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-[(tert-butilamino)metil]-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-(hidroksimetil)-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3- d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-[(izopropilamino)metil]-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[ 2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-[(etilamino)metil]-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4-il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrila; {1-(1-{[6-{[(2-metoksietil)(metil)amino]metil}-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4- il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-l-il]azetidin-3-il}acetonitrila; {1-(1-{[6-{[(3-hidroksipropil)(metil)amino]metil}-2-(trifluorometil)pirimidin-4-il]karbonil}piperidin-4- il)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-l-il]azetidin-3-il}acetonitrila; propil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-karboksilata; ciklobutilmetil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il{piperidin-1-karboksilata; etil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin-1- karboksilata; benzil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-karboksilata; izobutil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1-il}piperidin- 1-karboksilata; ciklopropilmetil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksilata; (1-metilciklopropil)metil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1- il]azetidin-1-il}piperidin-1-karboksilata; 2,4-difluorobenzil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksilata; 3,4-difluorobenzil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksilata; 3,5-difluorobenzil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksilata; ciklopentilmetil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksilata; i cikloheksilmetil 4-{3-(cijanometil)-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-1- il}piperidin-1-karboksilata; ili farmaceutski prihvatljive soli bilo kojeg od gore navedenih.
14. Jedinjenje prema patentnom zahtevu 1, koje je {1-{1-[3-Fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitril, ili njegova farmaceutski prihvatljiva so.
15. So prema patentnom zahtevu 1, koja je {1-{1-[3-Fluoro-2-(trifluorometil)izonikotinoil]piperidin-4-il}-3-[4-(7H-pirolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il]azetidin-3-il}acetonitrilna so adipinske kiseline.
16. So prema patentnom zahtevu 15, koja je karakterisana tačkom topljenja od oko 178 °C.
17. So prema patentnom zahtevu 15 ili 16 koja ima a) termogram diferencijalne skenirajuće kalorimetrije koji je karakterisan endotermnim pikom sa podešenom temperaturom od oko 176°C; ili b) termogram diferencijalne skenirajuće kalorimetrije suštinski kao što je prikazano na Slici 1.
18. So prema bilo kom od patentnih zahteva 15 do 17, koja ima termogram termogravimetrijske analize suštinski kao što je prikazano na slici 2.
19. So prema bilo kom od patentnih zahteva 15 do 18, koja ima a) obrazac rengenske difrakcije praha koji sadrži karakteristični pik izražen u stepenima 2Ɵ na oko 10.4; ili b) obrazac rengenske difrakcije praha koji sadrži karakteristični pik izražen u stepenima 2Ɵ na oko 6.9; ili c) obrazac rengenske difrakcije praha koji sadrži karakteristični pik izražen u stepenima 2Ɵ na oko 21.0; ili d) obrazac rengenske difrakcije praha koji sadrži karakteristični pik izražen u stepenima 2Ɵ na oko 23.3; ili e) obrazac rengenske difrakcije praha koji sadrži karakteristični pik izražen u stepenima 2Ɵ na oko 6.9, 10.4, 21.0, i 23.3; ili f) obrazac rengenske difrakcije praha suštinski kao što je prikazano na Slici 3.
20. Kompozicija koja sadrži jedinjenje ili so prema bilo kom od patentnih zahteva 1 do 19 i farmaceutski prihvatljiv nosač.
21. Jedinjenje ili so prema bilo kom od patentnih zahteva 1 do 19 za upotrebu u metodi modulacije aktivnosti JAK1.
22. Jedinjenje ili so za upotrebu prema patentnom zahtevu 21, pri čemu je navedeno jedinjenje, ili njegova farmaceutski prihvatljiva so, selektivno za JAK1 preko JAK2.
23. Jedinjenje ili so prema bilo kom od patentnih zahteva 1 do 19 za upotrebu u lečenju autoimune bolesti, kancera, mijeloproliferativnog poremećaja, inflamatorne bolesti, bolesti resorpcije kosti ili odbacivanja transplantata organa kod pacijenta kojem je to potrebno.
24. Jedinjenje ili so za upotrebu prema patentnom zahtevu 23, pri čemu a) navedena autoimuna bolest je kožni poremećaj, multipla skleroza, reumatoidni artritis, psorijatični artritis, juvenilni artritis, dijabetes tipa I, lupus, inflamatorna bolest creva, Kronova bolest, mijastenija gravis, imunoglobulinska nefropatija, miokarditis, ili autoimuni poremećaj štitnjače, ili b) navedena autoimuna bolest je reumatoidni artritis; ili c) navedena autoimuna bolest je kožni poremećaj; ili d) navedena autoimuna bolest je kožni poremećaj koji je atopijski dermatitis, psorijaza, senzitizacija kože, iritacija kože, osip na koži, kontaktni dermatitis ili alergijska kontaktna senzitizacija; ili e) navedeni kancer je solidni tumor; ili f) navedeni kancer je kancer prostate, kancer bubrega, kancer jetre, kancer dojke, kancer pluća, kancer štitnjače, Kapošijev sarkom, Kastlemanova bolest ili kancer gušterače; ili g) navedeni kancer je limfom, leukemija, ili multipli mijelom; ili h) navedeni mijeloproliferativni poremećaj je policitemija vera (PV), esencijalna trombocitemija (ET), mijeloidne metaplazije sa mijelofibrozom (MMM), primarna mijelofibroza (PMF), hronična mijelogena leukemija (CML), h) navedeni mijeloproliferativni poremećaj policitemija vera (PV), esencijalna trombocitemija (ET), mijeloidna metaplazija sa mijelofibrozom (MMM), primarna mijelofibroza (PMF), kronična mijelogena leukemija (CML),hronična mijelomonocitna leukemija (CMML), hipereozinofilni sindrom (HES), idiopatska mijelofibroza (MMF), ili sistemske bolesti mastocita (SMCD); ili i) navedeni mijeloproliferativni poremećaj je mijelofibroza; ili j) navedeni mijeloproliferativni poremećaj je primarna mijelofibroza (PMF); ili k) navedena resorpcija kosti je osteoporoza, osteoartritis, koštana resorpcija povezana s hormonalnom neravnotežom, koštana resorpcija povezana sa hormonskom terapijom, koštana resorpcija povezana sa autoimunim bolestima, ili koštana resorpcija povezana sa kancerom. 2
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Families Citing this family (133)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK3184526T3 (en) * 2005-12-13 2019-01-14 Incyte Holdings Corp PYRROLO [2,3-D] PYRIMIDINE DERIVATIVES AS A JANUS-KINASE INHIBITOR
DK2740731T3 (en) 2007-06-13 2016-04-11 Incyte Holdings Corp CRYSTALLINE SALTS OF JANUSKINASEINHIBITOREN (R) -3- (4- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -1H-pyrazol-1-yl) -3-CYCLOPENTYLPROPANNITRIL
CL2008001709A1 (es) 2007-06-13 2008-11-03 Incyte Corp Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras.
CL2009001884A1 (es) * 2008-10-02 2010-05-14 Incyte Holdings Corp Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco.
JOP20190230A1 (ar) 2009-01-15 2017-06-16 Incyte Corp طرق لاصلاح مثبطات انزيم jak و المركبات الوسيطة المتعلقة به
AU2010249443B2 (en) * 2009-05-22 2015-08-13 Incyte Holdings Corporation 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]octane- or heptane-nitrile as JAK inhibitors
MY156727A (en) 2009-05-22 2016-03-15 Incyte Corp N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
EP2448938B9 (en) 2009-06-29 2015-06-10 Incyte Corporation Pyrimidinones as pi3k inhibitors
TW201113285A (en) 2009-09-01 2011-04-16 Incyte Corp Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
AU2011224484A1 (en) 2010-03-10 2012-09-27 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
MY161078A (en) 2010-05-21 2017-04-14 Incyte Holdings Corp Topical formulation for a jak inhibitor
EP2640723A1 (en) 2010-11-19 2013-09-25 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
WO2012068440A1 (en) 2010-11-19 2012-05-24 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors
EP2655374B1 (en) 2010-12-20 2019-10-23 Incyte Holdings Corporation N-(1-(substituted-phenyl)ethyl)-9h-purin-6-amines as pi3k inhibitors
ES2547916T3 (es) 2011-02-18 2015-10-09 Novartis Pharma Ag Terapia de combinación de inhibidores de mTOR/JAK
KR20140040819A (ko) 2011-06-20 2014-04-03 인사이트 코포레이션 Ｊａｋ 저해제로서의 아제티디닐 페닐, 피리딜 또는 피라지닐 카르복스아미드 유도체
HK1198579A1 (en) 2011-08-10 2015-04-30 Novartis Pharma Ag Jak p13k/mtor combination therapy
TW201313721A (zh) * 2011-08-18 2013-04-01 Incyte Corp 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物
PL3513793T3 (pl) 2011-09-02 2021-09-20 Incyte Holdings Corporation Heterocykloaminy jako inhibitory pi3k
UA111854C2 (uk) * 2011-09-07 2016-06-24 Інсайт Холдінгс Корпорейшн Способи і проміжні сполуки для отримання інгібіторів jak
ES2640911T3 (es) * 2011-09-22 2017-11-07 Merck Sharp & Dohme Corp. Cicloalquilnitrilpirazolcarboxamidas como inhibidores de la quinasa Janus
AR090548A1 (es) 2012-04-02 2014-11-19 Incyte Corp Azaheterociclobencilaminas biciclicas como inhibidores de pi3k
WO2013173720A1 (en) * 2012-05-18 2013-11-21 Incyte Corporation Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
KR102160320B1 (ko) 2012-10-02 2020-09-28 에피테라퓨틱스 에이피에스 히스톤 탈메틸효소의 저해제
UA117572C2 (uk) 2012-11-01 2018-08-27 Інсайт Холдинґс Корпорейшн Трициклічні конденсовані похідні тіофену як інгібітори jak
PH12020551186B1 (en) 2012-11-15 2024-03-20 Incyte Holdings Corp Sustained-release dosage forms of ruxolitinib
JP6437452B2 (ja) 2013-01-14 2018-12-12 インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ Ｐｉｍキナーゼ阻害剤として有用な二環式芳香族カルボキサミド化合物
ME03780B (me) 2013-01-15 2021-04-20 Incyte Holdings Corp Jedinjenja tiazolkarboksamida i piridinkarboksamida korisna kao inhibitori pim kinaze
SI2961736T1 (en) 2013-02-27 2018-06-29 Gilead Sciences, Inc. Histone demethylase inhibitors
JP6397831B2 (ja) 2013-03-06 2018-09-26 インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ阻害剤の製造方法及びその中間体
US8669281B1 (en) 2013-03-14 2014-03-11 Alkermes Pharma Ireland Limited Prodrugs of fumarates and their use in treating various diseases
DK2970101T4 (da) 2013-03-14 2025-11-17 Alkermes Pharma Ireland Ltd Pro-drugs af fumarater og deres anvendelse i behandling af forskellige sygdomme
WO2014146249A1 (en) * 2013-03-19 2014-09-25 Merck Sharp & Dohme Corp. Geminally substituted cyanoethylpyrazolo pyridones as janus kinase inhibitors
JP6305510B2 (ja) 2013-03-19 2018-04-04 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． ヤヌスキナーゼ阻害剤としての非環式シアノエチルピラゾロピリドン
WO2014146246A1 (en) 2013-03-19 2014-09-25 Merck Sharp & Dohme Corp. Cycloalkyl nitrile pyrazolo pyridones as janus kinase inhibitors
AU2014234908B2 (en) 2013-03-19 2017-08-17 Merck Sharp & Dohme Corp. N-(2-cyano heterocyclyl)pyrazolo pyridones as Janus kinase inhibitors
EP2981252A4 (en) * 2013-04-04 2017-02-22 Olivia Newton-John Cancer Research Institute Methods of treating diseases characterized by excessive wnt signalling
TWI719401B (zh) 2013-05-17 2021-02-21 美商英塞特公司 作為jak抑制劑之聯吡唑衍生物
KR20160045081A (ko) * 2013-08-07 2016-04-26 인사이트 코포레이션 Jak1 억제제용 지속 방출 복용 형태
TW201529074A (zh) * 2013-08-20 2015-08-01 Incyte Corp 在ｃ-反應蛋白含量較高之實體腫瘤患者中的存活益處
EA201690458A1 (ru) 2013-08-23 2016-07-29 Инсайт Корпорейшн Фуро- и тиенопиридинкарбоксамиды, используемые в качестве ингибиторов pim-киназы
JP6367545B2 (ja) * 2013-12-17 2018-08-01 コンサート ファーマシューティカルズ インコーポレイテッド ルキソリチニブの重水素化誘導体
EP3110793B1 (en) 2014-02-24 2019-08-21 Alkermes Pharma Ireland Limited Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases
CN106456773A (zh) * 2014-02-28 2017-02-22 因赛特公司 用于治疗骨髓增生异常综合征的jak1抑制剂
LT3129021T (lt) * 2014-04-08 2020-12-10 Incyte Corporation B ląstelių piktybiškumo gydymas jak ir pi3k inhibitorių deriniu
MX2016014192A (es) 2014-04-30 2017-05-01 Incyte Corp Procesos para preparar un inhibidor de cinasas de janus 1 (jak1) y nuevas formas de este.
WO2015184305A1 (en) * 2014-05-30 2015-12-03 Incyte Corporation TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1
WO2015191677A1 (en) 2014-06-11 2015-12-17 Incyte Corporation Bicyclic heteroarylaminoalkyl phenyl derivatives as pi3k inhibitors
US9822124B2 (en) 2014-07-14 2017-11-21 Incyte Corporation Bicyclic heteroaromatic carboxamide compounds useful as Pim kinase inhibitors
US9580418B2 (en) 2014-07-14 2017-02-28 Incyte Corporation Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors
MX2017002451A (es) * 2014-08-27 2017-05-23 Gilead Sciences Inc Compuestos y metodos para inhibir histona desmetilasas.
US9586949B2 (en) 2015-02-09 2017-03-07 Incyte Corporation Aza-heteroaryl compounds as PI3K-gamma inhibitors
RS63963B1 (sr) 2015-02-27 2023-03-31 Incyte Holdings Corp Postupak pripreme pi3k inhibitora
US9732097B2 (en) 2015-05-11 2017-08-15 Incyte Corporation Process for the synthesis of a phosphoinositide 3-kinase inhibitor
WO2016183063A1 (en) 2015-05-11 2016-11-17 Incyte Corporation Crystalline forms of a pi3k inhibitor
US9840503B2 (en) 2015-05-11 2017-12-12 Incyte Corporation Heterocyclic compounds and uses thereof
WO2016196244A1 (en) 2015-05-29 2016-12-08 Incyte Corporation Pyridineamine compounds useful as pim kinase inhibitors
WO2017013270A1 (en) 2015-07-23 2017-01-26 Universite De Strasbourg Use of leptin signaling inhibitor for protecting kidneys from patients having ciliopathy
WO2017027717A1 (en) 2015-08-12 2017-02-16 Incyte Corporation Bicyclic fused pyrimidine compounds as tam inhibitors
WO2017035366A1 (en) 2015-08-26 2017-03-02 Incyte Corporation Pyrrolopyrimidine derivatives as tam inhibitors
AR105967A1 (es) 2015-09-09 2017-11-29 Incyte Corp Sales de un inhibidor de pim quinasa
WO2017059251A1 (en) 2015-10-02 2017-04-06 Incyte Corporation Heterocyclic compounds useful as pim kinase inhibitors
US11780848B2 (en) 2015-10-16 2023-10-10 Abbvie Inc. Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1- carboxamide and solid state forms thereof
US20170129902A1 (en) 2015-10-16 2017-05-11 Abbvie Inc. PROCESSES FOR THE PREPARATION OF (3S,4R)-3-ETHYL-4-(3H-IMIDAZO[1,2-alpha]PYRROLO[2,3-e]-PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL)PYRROLIDINE-1-CARBOXAMIDE AND SOLID STATE FORMS THEREOF
US10550126B2 (en) 2015-10-16 2020-02-04 Abbvie Inc. Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-A]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
US12365689B2 (en) 2015-10-16 2025-07-22 Abbvie Inc. Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
US11365198B2 (en) 2015-10-16 2022-06-21 Abbvie Inc. Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
US10065963B2 (en) 2015-11-06 2018-09-04 Incyte Corporation Heterocyclic compounds as PI3K-γ inhibitors
HK1250707B (zh) 2015-12-11 2020-07-03 四川科伦博泰生物医药股份有限公司 氮杂环丁烷衍生物、其制备方法及用途
US20170190689A1 (en) 2016-01-05 2017-07-06 Incyte Corporation Pyridine and pyridimine compounds as pi3k-gamma inhibitors
JP6770580B2 (ja) * 2016-01-26 2020-10-14 杭州華東医薬集団生物医薬有限公司Ｈａｎｇｚｈｏｕ Ｈｕａｄｏｎｇ Ｍｅｄｉｃｉｎｅ Ｇｒｏｕｐ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏ．， Ｌｔｄ． ピロロピリミジン５員環アザ環状誘導体およびその利用
WO2017162604A1 (en) 2016-03-21 2017-09-28 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for diagnosis and treatment of solar lentigo
EP3436461B1 (en) 2016-03-28 2023-11-01 Incyte Corporation Pyrrolotriazine compounds as tam inhibitors
US10138248B2 (en) 2016-06-24 2018-11-27 Incyte Corporation Substituted imidazo[2,1-f][1,2,4]triazines, substituted imidazo[1,2-a]pyridines, substituted imidazo[1,2-b]pyridazines and substituted imidazo[1,2-a]pyrazines as PI3K-γ inhibitors
US11397145B2 (en) * 2016-08-24 2022-07-26 The University Of Melbourne Diagnostic methods and device
GB201617871D0 (en) * 2016-10-21 2016-12-07 Sareum Limited Pharmaceutical compounds
US20180153922A1 (en) 2016-12-06 2018-06-07 New York Society For The Ruptured And Crippled Maintaining The Hospital For Special Surgery Inhibition of expansion and function of pathogenic age-associated b cells and use for the prevention and treatment of autoimmune disease
HRP20230069T1 (hr) 2017-01-17 2023-03-17 Astrazeneca Ab Selektivni inhibitori jak1
WO2018167283A1 (en) 2017-03-17 2018-09-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the diagnosis and treatment of pancreatic ductal adenocarcinoma associated neural remodeling
CN109422753B (zh) * 2017-09-03 2021-12-31 上海美志医药科技有限公司 一类具有抑制并降解酪氨酸蛋白激酶jak1或jak2活性的化合物
MY208007A (en) 2017-09-27 2025-04-04 Incyte Corp Salts of pyrrolotriazine derivatives useful as tam inhibitors
WO2019079469A1 (en) 2017-10-18 2019-04-25 Incyte Corporation CONDENSED IMIDAZOLE DERIVATIVES SUBSTITUTED WITH HYDROXY TERTIARY GROUPS AS INHIBITORS OF PI3K-GAMMA
CN109867676B (zh) * 2017-12-01 2020-10-30 北京普祺医药科技有限公司 一种吡咯并嘧啶衍生的化合物、药物组合物以及其用途
WO2019113487A1 (en) 2017-12-08 2019-06-13 Incyte Corporation Low dose combination therapy for treatment of myeloproliferative neoplasms
IL276295B2 (en) 2018-01-26 2024-02-01 Rapt Therapeutics Inc Modulators of chemokine receptors and their uses
CN112105608B (zh) 2018-01-30 2023-07-14 因赛特公司 制备(1-(3-氟-2-(三氟甲基)异烟碱基)哌啶-4-酮)的方法
BR112020016628A2 (pt) 2018-02-16 2020-12-15 Incyte Corporation Inibidores da via de jak1 para o tratamento de distúrbios relacionados a citocinas
MX2020009305A (es) 2018-03-08 2020-11-24 Novartis Ag Uso de un anticuerpo anti-p-selectina.
SMT202400306T1 (it) 2018-03-30 2024-09-16 Incyte Corp Trattamento dell'idrosadenite suppurativa utilizzando inibitori di jak.
WO2019191679A1 (en) 2018-03-30 2019-10-03 Incyte Corporation Biomarkers for inflammatory skin disease
SG11202010092XA (en) 2018-04-13 2020-11-27 Incyte Corp Biomarkers for graft-versus-host disease
AU2019277560B2 (en) 2018-06-01 2025-04-24 Incyte Corporation Dosing regimen for the treatment of PI3K related disorders
AR117600A1 (es) 2018-06-29 2021-08-18 Incyte Corp Formulaciones de un inhibidor de axl / mer
WO2020039401A1 (en) 2018-08-24 2020-02-27 Novartis Ag Treatment comprising il-1βeta binding antibodies and combinations thereof
CR20250050A (es) 2018-09-05 2025-03-19 Incyte Corp Formas cristalinas de un inhibidor de fosfoinositida 3–quinasa (pi3k) (divisional 2021-0165)
CN113490484B (zh) 2018-10-31 2024-08-23 因赛特公司 治疗血液疾病的组合疗法
WO2020092015A1 (en) 2018-11-02 2020-05-07 University Of Rochester Therapeutic mitigation of epithelial infection
KR101992148B1 (ko) 2018-11-30 2019-06-25 한승훈 안전벨트의 꼬임방지장치
PH12021551455A1 (en) 2018-12-19 2022-04-18 Incyte Corp Jak1 pathway inhibitors for the treatment of gastrointestinal disease
CN116473973A (zh) * 2018-12-24 2023-07-25 正大天晴药业集团股份有限公司 吡咯并嘧啶化合物的治疗用途及其固体药物组合物
JP2022524997A (ja) 2019-03-05 2022-05-11 インサイト・コーポレイション 慢性肺同種移植片機能不全の治療のためのｊａｋ１経路阻害剤
US12398141B2 (en) 2019-03-14 2025-08-26 Shanghai Synergy Pharmaceutical Sciences Co., Ltd JAK kinase inhibitor, preparation method for same, and applications thereof in field of medicine
US11624751B2 (en) 2019-03-19 2023-04-11 Incyte Corporation Biomarkers for vitiligo
WO2020257644A1 (en) 2019-06-21 2020-12-24 Constellation Pharmaceuticals, Inc. Methods of treating myeloproliferative disorders
WO2021091535A1 (en) 2019-11-05 2021-05-14 Constellation Pharmaceuticals, Inc. Treating myeloproliferative disorders with cpi-0610 and a jak inhibitor
WO2020256739A1 (en) 2019-06-21 2020-12-24 Constellation Pharmaceuticals, Inc. Methods of treating myeloproliferative disorders
WO2021053490A1 (en) 2019-09-16 2021-03-25 Novartis Ag Use of high-affinity, ligand-blocking, humanized anti-t-cell immunoglobulin domain and mucin domain-3 (tim-3) igg4 antibody for the treatment of myelofibrosis
KR20220063215A (ko) 2019-09-16 2022-05-17 노파르티스 아게 골수섬유증의 치료를 위한 mdm2 억제제의 용도
CN114761013A (zh) 2019-09-27 2022-07-15 迪斯克医药公司 治疗骨髓纤维化和相关病症的方法
US12360120B2 (en) 2019-10-10 2025-07-15 Incyte Corporation Biomarkers for graft-versus-host disease
CA3157499A1 (en) 2019-10-10 2021-04-15 Incyte Corporation Biomarkers for graft-versus-host disease
JP7518900B2 (ja) * 2019-10-16 2024-07-18 インサイト・コーポレイション 皮膚エリテマトーデス及び扁平苔癬（ｌｐ）の治療のためのｊａｋ１阻害剤の使用
US11992490B2 (en) * 2019-10-16 2024-05-28 Incyte Corporation Use of JAK1 inhibitors for the treatment of cutaneous lupus erythematosus and Lichen planus (LP)
KR20220107213A (ko) 2019-11-22 2022-08-02 인사이트 코포레이션 Alk2 억제제 및 jak2 억제제를 포함하는 병용 요법
EP4114401A1 (en) 2020-03-06 2023-01-11 Incyte Corporation Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors
KR20230012539A (ko) 2020-05-13 2023-01-26 디스크 메디슨, 인크. 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체
US11685731B2 (en) 2020-06-02 2023-06-27 Incyte Corporation Processes of preparing a JAK1 inhibitor
US11833155B2 (en) 2020-06-03 2023-12-05 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms
WO2022040172A1 (en) 2020-08-18 2022-02-24 Incyte Corporation Process and intermediates for preparing a jak1 inhibitor
CA3192099A1 (en) 2020-08-18 2022-02-24 Incyte Corporation Process and intermediates for preparing a jak inhibitor
EP4225317A1 (en) 2020-10-08 2023-08-16 Novartis AG Use of an erk inhibitor for the treatment of myelofibrosis
KR20230128472A (ko) 2020-12-04 2023-09-05 인사이트 코포레이션 피부 질환의 치료를 위한 비타민 d 유사체를 함유하는jak 억제제
CA3204374A1 (en) 2020-12-08 2022-06-16 Incyte Corporation Jak1 pathway inhibitors for the treatment of vitiligo
TW202237083A (zh) 2021-01-11 2022-10-01 美商英塞特公司 包含ｊａｋ路徑抑制劑及ｒｏｃｋ抑制劑之組合療法
TWI820622B (zh) 2021-03-04 2023-11-01 美商美國禮來大藥廠 Fgfr3抑制劑化合物
CN117098765A (zh) * 2021-03-15 2023-11-21 奇斯药制品公司 作为詹纳斯激酶抑制剂的杂环衍生物
MX2023013052A (es) 2021-05-03 2024-01-12 Incyte Corp Inhibidores de la via de la cinasa jano 1 (jak1) para el tratamiento del prurigo nodularis.
JP2024526762A (ja) 2021-07-12 2024-07-19 インサイト・コーポレイション Ｊａｋ阻害剤を調製するためのプロセス及び中間体
CN114149437A (zh) * 2021-12-24 2022-03-08 安徽大学 一种吡咯并嘧啶五元氮杂环衍生物及其制备方法和用途
EP4565229A1 (en) 2022-08-05 2025-06-11 Incyte Corporation Treatment of urticaria using jak inhibitors
TW202438061A (zh) 2023-03-16 2024-10-01 美商英塞特公司 用於治療氣喘之ｊａｋ１路徑抑制劑
TW202509019A (zh) * 2023-04-27 2025-03-01 香港商維泰瑞隆（香港）生物科技有限公司 Sarm1調節子、其製劑及用途
US20250325664A1 (en) 2024-04-22 2025-10-23 Incyte Corporation Combination therapy with an anti-colony stimulating factor 1 receptor antibody and a jak inhibitor

Family Cites Families (309)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2985589A (en) * 1957-05-22 1961-05-23 Universal Oil Prod Co Continuous sorption process employing fixed bed of sorbent and moving inlets and outlets
US3632836A (en) 1968-10-25 1972-01-04 Dow Chemical Co Solid curable polyepoxides modified with hydrolyzed liquid polyepoxides
US3832460A (en) 1971-03-19 1974-08-27 C Kosti Anesthetic-vasoconstrictor-antihistamine composition for the treatment of hypertrophied oral tissue
US4140755A (en) 1976-02-13 1979-02-20 Hoffmann-La Roche Inc. Sustained release tablet formulations
DE3036390A1 (de) 1980-09-26 1982-05-13 Troponwerke GmbH & Co KG, 5000 Köln Neue pyrrolo-pyrimidine, verfahren zu ihrer herstellung und ihre verwendung bei der herstellung von biologischen wirkstoffen
DE3220113A1 (de) * 1982-05-28 1983-12-01 Basf Ag, 6700 Ludwigshafen Difluormethoxiphenylthiophosphorsaeureester
US4402832A (en) * 1982-08-12 1983-09-06 Uop Inc. High efficiency continuous separation process
US4404335A (en) 1982-08-16 1983-09-13 The Dow Chemical Company Hydrolyzing epoxy resins in absence of solvent and in presence of oxalic acid and a phosphonium compound
US4548990A (en) 1983-08-15 1985-10-22 Ciba-Geigy Corporation Crosslinked, porous polymers for controlled drug delivery
US4498991A (en) * 1984-06-18 1985-02-12 Uop Inc. Serial flow continuous separation process
NL8403224A (nl) * 1984-10-24 1986-05-16 Oce Andeno Bv Dioxafosforinanen, de bereiding ervan en de toepassing voor het splitsen van optisch actieve verbindingen.
CA1306260C (en) 1985-10-18 1992-08-11 Shionogi & Co., Ltd. Condensed imidazopyridine derivatives
JPH0710876Y2 (ja) 1989-08-31 1995-03-15 石垣機工株式会社 スクリュープレスにおける脱水筒の洗浄装置
ES2087916T3 (es) * 1989-10-11 1996-08-01 Teijin Ltd Derivado de pirimidina biciclico, metodo para producir el mismo, y preparacion farmaceutica que contiene el mismo como ingrediente activo.
US5403593A (en) 1991-03-04 1995-04-04 Sandoz Ltd. Melt granulated compositions for preparing sustained release dosage forms
IT1258781B (it) * 1992-01-16 1996-02-29 Zambon Spa Composizione farmaceutica oftalmica contenente n-acetilcisteina e polivinilalcol
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
FR2695126B1 (fr) 1992-08-27 1994-11-10 Sanofi Elf Dérivés d'acide thiényl ou pyrrolyl carboxyliques, leur préparation et médicaments les contenant.
AU671491B2 (en) 1992-12-18 1996-08-29 F. Hoffmann-La Roche Ag N-oxycarbonyl substituted 5'-deoxy-5-fluorcytidines
JPH0710876A (ja) 1993-06-24 1995-01-13 Teijin Ltd ４位に環状アミノ基を有するピロロ［２，３―ｄ］ピリミジン
USH1439H (en) 1993-10-18 1995-05-02 The Dow Chemical Company Method to increase the level of α-glycol in liquid epoxy resin
EP0727217A3 (en) 1995-02-10 1997-01-15 Suntory Ltd Pharmaceutical and cosmetic compositions containing God-type ellagitannin as an active ingredient
IL117580A0 (en) 1995-03-29 1996-07-23 Merck & Co Inc Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them
US5856326A (en) * 1995-03-29 1999-01-05 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
ES2167586T3 (es) 1995-07-05 2002-05-16 Du Pont Pirimidinonas fungicidas.
JP4146514B2 (ja) 1995-07-06 2008-09-10 ノバルティス アクチエンゲゼルシャフト ピロロピリミジン類およびその製造方法
US5630943A (en) * 1995-11-30 1997-05-20 Merck Patent Gesellschaft Mit Beschrankter Haftung Discontinuous countercurrent chromatographic process and apparatus
GB9604361D0 (en) 1996-02-29 1996-05-01 Pharmacia Spa 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors
EP0906099A4 (en) 1996-04-03 2001-02-07 Merck & Co Inc METHOD FOR TREATING CANCER
CA2251955A1 (en) 1996-04-18 1997-10-23 Nancy E. Kohl A method of treating cancer
US5795909A (en) 1996-05-22 1998-08-18 Neuromedica, Inc. DHA-pharmaceutical agent conjugates of taxanes
JP2000508335A (ja) 1996-05-30 2000-07-04 メルク エンド カンパニー インコーポレーテッド 癌の治療方法
US6624138B1 (en) 2001-09-27 2003-09-23 Gp Medical Drug-loaded biological material chemically treated with genipin
CA2286239A1 (en) 1997-04-07 1998-10-15 Merck & Co., Inc. A method of treating cancer
US6063284A (en) 1997-05-15 2000-05-16 Em Industries, Inc. Single column closed-loop recycling with periodic intra-profile injection
US6060038A (en) * 1997-05-15 2000-05-09 Merck & Co., Inc. Radiolabeled farnesyl-protein transferase inhibitors
EP1001782A4 (en) * 1997-08-11 2002-01-30 Boehringer Ingelheim Pharma 5,6-HETEROARYL-DIPYRIDO 2,3- $ i (b): 3 ', 2' - $ i (f)] AZEPINES AND THEIR USE IN THE PREVENTION OR TREATMENT OF HIV INFECTION
US7153845B2 (en) 1998-08-25 2006-12-26 Columbia Laboratories, Inc. Bioadhesive progressive hydration tablets
US6075056A (en) 1997-10-03 2000-06-13 Penederm, Inc. Antifungal/steroid topical compositions
US6025366A (en) 1998-04-02 2000-02-15 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
JP2002517396A (ja) 1998-06-04 2002-06-18 アボット・ラボラトリーズ 細胞接着阻害抗炎症性化合物
US6232320B1 (en) * 1998-06-04 2001-05-15 Abbott Laboratories Cell adhesion-inhibiting antiinflammatory compounds
PT1087970E (pt) 1998-06-19 2004-06-30 Pfizer Prod Inc Compostos pirrolo¬2,3-d|pirimidina
PA8474101A1 (es) 1998-06-19 2000-09-29 Pfizer Prod Inc Compuestos de pirrolo [2,3-d] pirimidina
ATE459616T1 (de) 1998-08-11 2010-03-15 Novartis Ag Isochinoline derivate mit angiogenesis-hemmender wirkung
JP2000119271A (ja) 1998-08-12 2000-04-25 Hokuriku Seiyaku Co Ltd １ｈ―イミダゾピリジン誘導体
DK1109534T3 (da) 1998-09-10 2003-06-10 Nycomed Danmark As Farmaceutiske præparater med quick release af den aktive substans
US6413419B1 (en) * 1998-10-29 2002-07-02 Institut Francais Du Petrole Process and device for separation with variable-length chromatographic
FR2785196B1 (fr) 1998-10-29 2000-12-15 Inst Francais Du Petrole Procede et dispositif de separation avec des zones chromatographiques a longueur variable
US6375839B1 (en) * 1998-10-29 2002-04-23 Institut Francais Du Petrole Process and device for separation with variable-length chromatographic zones
US6133031A (en) 1999-08-19 2000-10-17 Isis Pharmaceuticals Inc. Antisense inhibition of focal adhesion kinase expression
JP2002538121A (ja) 1999-03-03 2002-11-12 メルク エンド カムパニー インコーポレーテッド プレニルタンパク質トランスフェラーゼの阻害剤
GB9905075D0 (en) 1999-03-06 1999-04-28 Zeneca Ltd Chemical compounds
US6217895B1 (en) * 1999-03-22 2001-04-17 Control Delivery Systems Method for treating and/or preventing retinal diseases with sustained release corticosteroids
US6239113B1 (en) * 1999-03-31 2001-05-29 Insite Vision, Incorporated Topical treatment or prevention of ocular infections
AU3565999A (en) 1999-04-16 2000-11-02 Coelacanth Chemical Corporation Synthesis of azetidine derivatives
US6915718B2 (en) * 1999-09-02 2005-07-12 United Parts Fhs Automobil Systeme Gmbh Selector handle in a motor vehicle
US6921763B2 (en) * 1999-09-17 2005-07-26 Abbott Laboratories Pyrazolopyrimidines as therapeutic agents
EP1221443B1 (en) * 1999-10-13 2004-09-01 Banyu Pharmaceutical Co., Ltd. Substituted imidazolidinone derivatives
US7235258B1 (en) 1999-10-19 2007-06-26 Nps Pharmaceuticals, Inc. Sustained-release formulations for treating CNS-mediated disorders
UA72290C2 (uk) 1999-12-10 2005-02-15 Пфайзер Продактс Інк. СПОЛУКИ ПІРОЛО[2.3-d]ПІРИМІДИНУ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ (ВАРІАНТИ), СПОСІБ ІНГІБУВАННЯ ПРОТЕЇНКІНАЗ АБО JANUS КІНАЗИ 3 (ВАРІАНТИ)
CN1615873A (zh) * 1999-12-24 2005-05-18 阿文蒂斯药物有限公司 氮杂吲哚类化合物
GB0004890D0 (en) 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
US7235551B2 (en) * 2000-03-02 2007-06-26 Smithkline Beecham Corporation 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases
DK1142566T3 (da) 2000-04-07 2004-02-09 Medidom Lab Oftalmologiske formuleringer på basis af ciclosporin, hyaluronsyre og polysorbat
AU4878601A (en) 2000-04-20 2001-11-07 Mitsubishi Corporation Aromatic amide compounds
EP1278748B1 (en) 2000-04-25 2011-03-23 ICOS Corporation Inhibitors of human phosphatidyl-inositol 3-kinase delta
US7498304B2 (en) * 2000-06-16 2009-03-03 Curis, Inc. Angiogenesis-modulating compositions and uses
CA2412215A1 (en) 2000-06-16 2001-12-27 Curis, Inc. Angiogenesis-modulating compositions and uses
US6335342B1 (en) 2000-06-19 2002-01-01 Pharmacia & Upjohn S.P.A. Azaindole derivatives, process for their preparation, and their use as antitumor agents
JP5000831B2 (ja) * 2000-06-23 2012-08-15 田辺三菱製薬株式会社 抗腫瘍作用増強剤
CN100351253C (zh) 2000-06-26 2007-11-28 辉瑞产品公司 作为免疫抑制剂的吡咯并[2,3－d]嘧啶化合物
JP4188078B2 (ja) 2000-06-28 2008-11-26 スミスクライン ビーチャム ピー エル シー 湿式粉砕法
WO2002016370A1 (en) 2000-08-22 2002-02-28 Hokuriku Seiyaku Co., Ltd. 1h-imidazopyridine derivatives
US20020111353A1 (en) * 2000-12-05 2002-08-15 Mark Ledeboer Inhibitors of c-Jun N-terminal kinases (JNK) and other protein kinases
GB0100622D0 (en) 2001-01-10 2001-02-21 Vernalis Res Ltd Chemical compounds V111
US20040077654A1 (en) * 2001-01-15 2004-04-22 Bouillot Anne Marie Jeanne Aryl piperidine and piperazine derivatives as inducers of ldl-receptor expression
WO2002060492A1 (en) 2001-01-30 2002-08-08 Cytopia Pty Ltd Methods of inhibiting kinases
AU2002308748A1 (en) 2001-05-16 2002-11-25 Vertex Pharmaceuticals Incorporated Heterocyclic substituted pyrazoles as inhibitors of src and other protein kinases
US7301023B2 (en) 2001-05-31 2007-11-27 Pfizer Inc. Chiral salt resolution
GB0115109D0 (en) 2001-06-21 2001-08-15 Aventis Pharma Ltd Chemical compounds
GB0115393D0 (en) 2001-06-23 2001-08-15 Aventis Pharma Ltd Chemical compounds
WO2003011285A1 (en) 2001-08-01 2003-02-13 Merck & Co., Inc. BENZIMIDAZO[4,5-f]ISOQUINOLINONE DERIVATIVES
AU2002337142B2 (en) 2001-09-19 2007-10-11 Aventis Pharma S.A. Indolizines as kinase protein inhibitors
US6429231B1 (en) 2001-09-24 2002-08-06 Bradley Pharmaceuticals, Inc. Compositions containing antimicrobials and urea for the treatment of dermatological disorders and methods for their use
EP1441737B1 (en) 2001-10-30 2006-08-09 Novartis AG Staurosporine derivatives as inhibitors of flt3 receptor tyrosine kinase activity
JP2003155285A (ja) 2001-11-19 2003-05-27 Toray Ind Inc 環状含窒素誘導体
WO2003048111A1 (fr) 2001-11-30 2003-06-12 Teijin Limited Procede pour produire un compose d'acide 5-(3-cyanophenyl)-3-formylbenzoique
GT200200234A (es) 2001-12-06 2003-06-27 Compuestos cristalinos novedosos
US6995144B2 (en) * 2002-03-14 2006-02-07 Eisai Co., Ltd. Nitrogen containing heterocyclic compounds and medicines containing the same
WO2003088952A1 (en) 2002-04-15 2003-10-30 Adams Laboratories, Inc. Sustained release of guaifenesin combination drugs
TW200403058A (en) * 2002-04-19 2004-03-01 Bristol Myers Squibb Co Heterocyclo inhibitors of potassium channel function
WO2003091246A1 (en) * 2002-04-26 2003-11-06 Vertex Pharmaceuticals Incorporated Pyrrole derivatives as inhibitors of erk2 and uses thereof
AU2003241326B2 (en) 2002-05-02 2008-05-01 Merck & Co., Inc. Tyrosine kinase inhibitors
WO2003094888A1 (en) * 2002-05-07 2003-11-20 Control Delivery Systems, Inc. Processes for forming a drug delivery device
DE60317198T2 (de) 2002-05-23 2008-12-04 Cytopia Research Pty. Ltd., Richmond Proteinkinaseinhibitoren
PE20040522A1 (es) 2002-05-29 2004-09-28 Novartis Ag Derivados de diarilurea dependientes de la cinasa de proteina
CA2490340A1 (en) 2002-06-26 2004-01-08 Idemitsu Kosan Co., Ltd. Hydrogenated copolymer, production process for the same and hot melt adhesive composition using the same
GB0215676D0 (en) 2002-07-05 2002-08-14 Novartis Ag Organic compounds
GB0215844D0 (en) 2002-07-09 2002-08-14 Novartis Ag Organic compounds
EP1541563A4 (en) * 2002-07-10 2007-11-07 Ono Pharmaceutical Co ANTAGONIST OF CCR4 AND CORRESPONDING MEDICINAL USE
KR20050057175A (ko) 2002-09-20 2005-06-16 알콘, 인코퍼레이티드 안구건조증 치료용 사이토카인 합성 저해제의 용도
US20040204404A1 (en) 2002-09-30 2004-10-14 Robert Zelle Human N-type calcium channel blockers
DE60316013T2 (de) 2002-11-04 2008-05-29 Vertex Pharmaceuticals Inc., Cambridge Heteroaryl-pyrimidinderivate als jak-inhibitoren
US8034831B2 (en) 2002-11-06 2011-10-11 Celgene Corporation Methods for the treatment and management of myeloproliferative diseases using 4-(amino)-2-(2,6-Dioxo(3-piperidyl)-isoindoline-1,3-dione in combination with other therapies
TWI335913B (en) 2002-11-15 2011-01-11 Vertex Pharma Diaminotriazoles useful as inhibitors of protein kinases
US20040099204A1 (en) 2002-11-25 2004-05-27 Nestor John J. Sheet, page, line, position marker
KR20050086784A (ko) 2002-11-26 2005-08-30 화이자 프로덕츠 인크. 이식 거부반응의 치료 방법
UA80767C2 (en) 2002-12-20 2007-10-25 Pfizer Prod Inc Pyrimidine derivatives for the treatment of abnormal cell growth
UY28126A1 (es) * 2002-12-24 2004-06-30 Alcon Inc Uso de glucocorticoides selectivos para la superficie ocular en el tratamiento de la sequedad ocular
US7135493B2 (en) 2003-01-13 2006-11-14 Astellas Pharma Inc. HDAC inhibitor
US7167750B2 (en) 2003-02-03 2007-01-23 Enteromedics, Inc. Obesity treatment with electrically induced vagal down regulation
WO2004072063A1 (en) 2003-02-07 2004-08-26 Vertex Pharmaceuticals Incorporated Heteroaryl substituted pyrolls useful as inhibitors of protein kinases
GB0305929D0 (en) 2003-03-14 2003-04-23 Novartis Ag Organic compounds
WO2004092154A1 (en) 2003-04-03 2004-10-28 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of protein kinases
SE0301372D0 (sv) 2003-05-09 2003-05-09 Astrazeneca Ab Novel compounds
SE0301373D0 (sv) 2003-05-09 2003-05-09 Astrazeneca Ab Novel compounds
FR2857454B1 (fr) 2003-07-08 2006-08-11 Aventis Pasteur Dosage des acides techoiques des bacteries gram+
US20050043346A1 (en) 2003-08-08 2005-02-24 Pharmacia Italia S.P.A. Pyridylpyrrole derivatives active as kinase inhibitors
US8362017B2 (en) 2003-08-29 2013-01-29 Exelixis, Inc. C-kit modulators and methods of use
EP1678147B1 (en) 2003-09-15 2012-08-08 Lead Discovery Center GmbH Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases
AR045944A1 (es) 2003-09-24 2005-11-16 Novartis Ag Derivados de isoquinolina 1.4-disustituidas
DE602004030470D1 (de) * 2003-10-24 2011-01-20 Santen Pharmaceutical Co Ltd Therapeutisches mittel für keratokonjunktive erkrankungen
US7387793B2 (en) 2003-11-14 2008-06-17 Eurand, Inc. Modified release dosage forms of skeletal muscle relaxants
MY141220A (en) 2003-11-17 2010-03-31 Astrazeneca Ab Pyrazole derivatives as inhibitors of receptor tyrosine kinases
WO2005051393A1 (en) 2003-11-25 2005-06-09 Pfizer Products Inc. Method of treatment of atherosclerosis
CA2549485A1 (en) 2003-12-17 2005-07-07 Pfizer Products Inc. Pyrrolo [2,3-d] pyrimidine compounds for treating transplant rejection
ES2527118T3 (es) 2003-12-19 2015-01-20 Plexxikon Inc. Compuestos y procedimientos de desarrollo de moduladores de Ret
DE602004016211D1 (en) 2003-12-19 2008-10-09 Schering Corp Thiadiazole als cxc- und cc-chemokinrezeptorliganden
AU2004303602C1 (en) 2003-12-23 2009-05-28 Astex Therapeutics Limited Pyrazole derivatives as protein kinase modulators
US20050187389A1 (en) * 2004-01-13 2005-08-25 Ambit Biosciences Corporation Pyrrolopyrimidine derivatives and analogs and their use in the treatment and prevention of diseases
CA2559285A1 (en) 2004-03-18 2005-09-29 Brigham And Women's Hospital, Inc. Methods for the treatment of synucleinopathies
PT1730146E (pt) 2004-03-30 2011-07-11 Vertex Pharma Azaindoles úteis como inibidores de jak e outras proteínas quinases
JP5213229B2 (ja) 2004-04-23 2013-06-19 エグゼリクシス， インコーポレイテッド キナーゼ調節因子および使用方法
WO2005105814A1 (en) 2004-04-28 2005-11-10 Incyte Corporation Tetracyclic inhibitors of janus kinases
WO2005105988A2 (en) 2004-04-28 2005-11-10 Vertex Pharmaceuticals Incorporated Crystal structure of human jak3 kinase domain complex and binding pockets thereof
JP2007536310A (ja) 2004-05-03 2007-12-13 ノバルティス アクチエンゲゼルシャフト Ｓ１ｐ受容体アゴニストおよびｊａｋ３キナーゼ阻害剤を含む、組合せ剤
JP2007537296A (ja) 2004-05-14 2007-12-20 アボット・ラボラトリーズ 治療薬としてのキナーゼ阻害薬
PE20060426A1 (es) 2004-06-02 2006-06-28 Schering Corp DERIVADOS DE ACIDO TARTARICO COMO INHIBIDORES DE MMPs, ADAMs, TACE Y TNF-alfa
TW200610762A (en) 2004-06-10 2006-04-01 Irm Llc Compounds and compositions as protein kinase inhibitors
EP1760071A4 (en) * 2004-06-23 2008-03-05 Ono Pharmaceutical Co COMPOUND WITH S1P RECEPTOR BINDING ABILITY AND USE THEREOF
EP2325184A1 (en) 2004-06-30 2011-05-25 Vertex Pharmceuticals Incorporated Azaindoles useful as inhibitors of protein kinases
US7138423B2 (en) 2004-07-20 2006-11-21 Bristol-Myers Squibb Company Arylpyrrolidine derivatives as NK-1 /SSRI antagonists
FR2873691B1 (fr) * 2004-07-29 2006-10-06 Sanofi Synthelabo Derives d'amino-piperidine, leur preparation et leur application en therapeutique
WO2006013114A1 (en) 2004-08-06 2006-02-09 Develogen Aktiengesellschaft Use of a timp-2 secreted protein product for preventing and treating pancreatic diseases and/or obesity and/or metabolic syndrome
WO2006022459A1 (en) 2004-08-23 2006-03-02 Mogam Biotechnology Institute Primer and probe for detection of sars coronavirus, kit comprising the primer and/or the probe, and detection method thereof
US20070054916A1 (en) 2004-10-01 2007-03-08 Amgen Inc. Aryl nitrogen-containing bicyclic compounds and methods of use
JP2008515939A (ja) * 2004-10-13 2008-05-15 エフ．ホフマン−ラ ロシュ アーゲー Ｃｄｋ２及び血管形成の阻害剤として、及び乳癌、結腸癌及び前立腺癌の治療に有用な２置換ピラゾロベンゾジアゼピン
UY29177A1 (es) 2004-10-25 2006-05-31 Astex Therapeutics Ltd Derivados sustituidos de purina, purinona y deazapurina, composiciones que los contienen métodos para su preparación y sus usos
MY179032A (en) 2004-10-25 2020-10-26 Cancer Research Tech Ltd Ortho-condensed pyridine and pyrimidine derivatives (e.g.purines) as protein kinase inhibitors
KR20070090172A (ko) 2004-11-04 2007-09-05 버텍스 파마슈티칼스 인코포레이티드 단백질 키나아제의 억제제로서 유용한피라졸로[1,5-ａ]피리미딘
WO2006056399A2 (en) 2004-11-24 2006-06-01 Novartis Ag Combinations of jak inhibitors and at least one of bcr-abl, flt-3, fak or raf kinase inhibitors
US7517870B2 (en) * 2004-12-03 2009-04-14 Fondazione Telethon Use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization
US20060128803A1 (en) * 2004-12-14 2006-06-15 Alcon, Inc. Method of treating dry eye disorders using 13(S)-HODE and its analogs
AR054416A1 (es) 2004-12-22 2007-06-27 Incyte Corp Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas.
TW200635899A (en) 2004-12-22 2006-10-16 Astrazeneca Ab Chemical compounds
EP1844037A1 (en) 2005-01-20 2007-10-17 Pfizer Limited Chemical compounds
WO2006096270A1 (en) 2005-02-03 2006-09-14 Vertex Pharmaceuticals Incorporated Pyrrolopyrimidines useful as inhibitors of protein kinase
US7683171B2 (en) 2005-02-04 2010-03-23 Bristol-Myers Squibb Company 1H-imidazo[4,5-d]thieno[3,2-b]pyridine based tricyclic compounds and pharmaceutical compositions comprising same
AU2006227790B2 (en) 2005-03-15 2009-09-10 Irm Llc Compounds and compositions as protein kinase inhibitors
KR20080013886A (ko) 2005-04-05 2008-02-13 파마코페이아, 인코포레이티드 면역억제용 퓨린 및 이미다조피리딘 유도체
GB0510139D0 (en) 2005-05-18 2005-06-22 Addex Pharmaceuticals Sa Novel compounds B1
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
EP1881983B1 (en) * 2005-05-20 2012-01-11 Vertex Pharmaceuticals, Inc. Pyrrolopyridines useful as inhibitors of protein kinase
US7491732B2 (en) 2005-06-08 2009-02-17 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
WO2006136823A1 (en) 2005-06-21 2006-12-28 Astex Therapeutics Limited Heterocyclic containing amines as kinase b inhibitors
UA95244C2 (ru) 2005-06-22 2011-07-25 Плексикон, Инк. Соединения и способ модулирования активности киназ, и показания для их применения
EP2251341A1 (en) 2005-07-14 2010-11-17 Astellas Pharma Inc. Heterocyclic Janus kinase 3 inhibitors
FR2889662B1 (fr) 2005-08-11 2011-01-14 Galderma Res & Dev Emulsion de type huile-dans-eau pour application topique en dermatologie
US20070049591A1 (en) 2005-08-25 2007-03-01 Kalypsys, Inc. Inhibitors of MAPK/Erk Kinase
CA2621261C (en) * 2005-09-22 2014-05-20 Incyte Corporation Azepine inhibitors of janus kinases
NZ567133A (en) 2005-09-30 2011-07-29 Vertex Pharma Deazapurines useful as inhibitors of janus kinases
WO2007044894A2 (en) 2005-10-11 2007-04-19 Chembridge Research Laboratories, Inc. Cell-free protein expression systems and methods of use thereof
AU2006300182B2 (en) 2005-10-14 2012-01-19 Sumitomo Chemical Company, Limited Hydrazide compound and pesticidal use of the same
RU2463302C2 (ru) 2005-10-28 2012-10-10 Астразенека Аб Производные 4-(3-аминопиразол)пиримидина для применения в качестве ингибиторов тирозинкиназы для лечения злокачественного новообразования
NZ592990A (en) 2005-11-01 2013-01-25 Targegen Inc Bi-aryl meta-pyrimidine inhibitors of kinases
US9006224B2 (en) 2005-11-21 2015-04-14 Novartis Ag Neuroendocrine tumor treatment
WO2007062459A1 (en) 2005-11-29 2007-06-07 Cytopia Research Pty Ltd Selective kinase inhibitors based on pyridine scaffold
US20130137681A1 (en) * 2005-12-13 2013-05-30 Incyte Corporation HETEROARYL SUBSTITUTED PYRROLO[2,3-b]PYRIDINES AND PYRROLO[2,3-b]PYRIMIDINES AS JANUS KINASE INHIBITORS
DK3184526T3 (en) * 2005-12-13 2019-01-14 Incyte Holdings Corp PYRROLO [2,3-D] PYRIMIDINE DERIVATIVES AS A JANUS-KINASE INHIBITOR
JP2009521504A (ja) 2005-12-22 2009-06-04 スミスクライン・ビーチャム・コーポレイション Ａｋｔ活性阻害剤
MX2008008320A (es) * 2005-12-23 2008-09-03 Smithkline Beecham Corp Inhibidores de azaindol de aurora cinasas.
JP4643455B2 (ja) 2006-01-12 2011-03-02 株式会社ユニバーサルエンターテインメント 遊技システム
NZ601687A (en) 2006-01-17 2014-03-28 Vertex Pharma Azaindoles useful as inhibitors of janus kinases
CA2635899A1 (en) * 2006-01-19 2007-07-26 Osi Pharmaceuticals, Inc. Fused heterobicyclic kinase inhibitors
WO2007090141A2 (en) 2006-02-01 2007-08-09 Smithkline Beecham Corporation Pyrrolo [2, 3, b] pyridine derivatives useful as raf kinase inhibitors
US7745477B2 (en) 2006-02-07 2010-06-29 Hoffman-La Roche Inc. Heteroaryl and benzyl amide compounds
WO2007097770A1 (en) 2006-02-24 2007-08-30 Teva Pharmaceutical Industries Ltd. Metoprolol succinate e.r. tablets and methods for their preparation
AU2007225836A1 (en) * 2006-03-10 2007-09-20 Ono Pharmaceutical Co., Ltd. Nitrogenated heterocyclic derivative, and pharmaceutical agent comprising the derivative as active ingredient
EP2003132B1 (en) * 2006-04-03 2014-03-05 Astellas Pharma Inc. Oxadiazole derivatives as S1P1 agonists
KR20090018895A (ko) * 2006-04-05 2009-02-24 버텍스 파마슈티칼스 인코포레이티드 야누스 키나제의 억제제로서 유용한 데아자푸린
US20090124636A1 (en) 2006-04-12 2009-05-14 Pfizer Inc. Chemical compounds
WO2007129195A2 (en) 2006-05-04 2007-11-15 Pfizer Products Inc. 4-pyrimidine-5-amino-pyrazole compounds
EP2040704A2 (en) 2006-05-18 2009-04-01 Bayer Healthcare Ag Pharmaceutical compositions comprising implitapide and methods of using same
US7691811B2 (en) * 2006-05-25 2010-04-06 Bodor Nicholas S Transporter-enhanced corticosteroid activity and methods and compositions for treating dry eye
TWI398252B (zh) 2006-05-26 2013-06-11 Novartis Ag 吡咯并嘧啶化合物及其用途
NZ573174A (en) 2006-06-01 2012-01-12 Msd Consumer Care Inc Sustained release pharmaceutical dosage form containing phenylephrine
US20080021217A1 (en) * 2006-07-20 2008-01-24 Allen Borchardt Heterocyclic inhibitors of rho kinase
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
US8492378B2 (en) * 2006-08-03 2013-07-23 Takeda Pharmaceutical Company Limited GSK-3β inhibitor
EP2061762B1 (en) * 2006-08-16 2011-07-27 Boehringer Ingelheim International GmbH Pyrazine compounds, their use and methods of preparation
CA2662091A1 (en) 2006-09-08 2008-03-13 Novartis Ag N-biaryl (hetero) arylsulphonamide derivatives useful in the treatment of diseases mediated by lymphocytes interactions
WO2008035376A2 (en) 2006-09-19 2008-03-27 Council Of Scientific & Industrial Research A novel bio-erodible insert for ophthalmic applications and a process for the preparation thereof
CL2007002867A1 (es) * 2006-10-04 2008-06-27 Pharmacopeia Inc Compuestos derivados de 2-(bencimidazolil)purina, inhibidores de janus quinasa 3; composicion farmaceutica que los contiene; y su uso para tratar enfermedades autoinmune, inflamatorias, cardiovasculares, rechazo de implante, entre otras.
WO2008043031A1 (en) 2006-10-04 2008-04-10 Pharmacopeia, Inc. 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression
US20120225057A1 (en) 2006-10-11 2012-09-06 Deciphera Pharmaceuticals, Llc Methods and compositions for the treatment of myeloproliferative diseases and other proliferative diseases
MX2009004700A (es) 2006-11-06 2009-05-15 Supergen Inc Derivados de imidazo[1,2-b]piridazin y pirazolo[1,5-a] pirimidina y su uso como inhibidores de proteina cinasa.
US20080119496A1 (en) * 2006-11-16 2008-05-22 Pharmacopeia Drug Discovery, Inc. 7-Substituted Purine Derivatives for Immunosuppression
MX2009005144A (es) 2006-11-22 2009-05-27 Incyte Corp Imidazotriazinas e imidazopirimidinas como inhibidores de cinasa.
WO2008067119A2 (en) 2006-11-27 2008-06-05 Smithkline Beecham Corporation Novel compounds
EP2109364A4 (en) 2006-12-15 2010-04-14 Abbott Lab NOVEL OXADIAZONE COMPOUNDS
JP5528812B2 (ja) * 2006-12-20 2014-06-25 アムジエン・インコーポレーテツド 複素環式化合物ならびに炎症、血管形成および癌の治療におけるこれらの使用
EP2125781A2 (en) 2006-12-20 2009-12-02 Amgen Inc. Substituted heterocycles and methods of use
EP2121692B1 (en) 2006-12-22 2013-04-10 Incyte Corporation Substituted heterocycles as janus kinase inhibitors
KR101433152B1 (ko) 2006-12-22 2014-08-22 시그마타우 인두스트리에 파르마슈티케 리우니테 에스.피.에이. 안과용 약물의 전달에 유용한 젤
KR20080062876A (ko) 2006-12-29 2008-07-03 주식회사 대웅제약 신규한 항진균성 트리아졸 유도체
WO2008082839A2 (en) 2006-12-29 2008-07-10 Abbott Laboratories Pim kinase inhibitors as cancer chemotherapeutics
WO2008082840A1 (en) 2006-12-29 2008-07-10 Abbott Laboratories Pim kinase inhibitors as cancer chemotherapeutics
CN101679266B (zh) 2007-03-01 2015-05-06 诺华股份有限公司 Pim激酶抑制剂及其应用方法
EP2137184B1 (en) 2007-04-03 2013-05-08 Array Biopharma, Inc. Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors
US8188178B2 (en) 2007-05-07 2012-05-29 3M Innovative Properties Company Cold shrinkable article including an epichlorohydrin composition
GB0709031D0 (en) 2007-05-10 2007-06-20 Sareum Ltd Pharmaceutical compounds
WO2008145681A2 (en) 2007-05-31 2008-12-04 Boehringer Ingelheim International Gmbh Ccr2 receptor antagonists and uses thereof
GB0710528D0 (en) 2007-06-01 2007-07-11 Glaxo Group Ltd Novel compounds
CL2008001709A1 (es) 2007-06-13 2008-11-03 Incyte Corp Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras.
DK2740731T3 (en) 2007-06-13 2016-04-11 Incyte Holdings Corp CRYSTALLINE SALTS OF JANUSKINASEINHIBITOREN (R) -3- (4- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -1H-pyrazol-1-yl) -3-CYCLOPENTYLPROPANNITRIL
KR101258316B1 (ko) 2007-07-11 2013-04-30 화이자 인코포레이티드 안구 건조증 치료용 약학 조성물 및 방법
JP4792126B2 (ja) * 2007-08-01 2011-10-12 ファイザー・インク ピラゾール化合物およびＲａｆ阻害剤としてのその使用
WO2009049028A1 (en) 2007-10-09 2009-04-16 Targegen Inc. Pyrrolopyrimidine compounds and their use as janus kinase modulators
US20110263664A1 (en) 2007-11-15 2011-10-27 Musc Foundation For Research Development Inhibitors of PIM-1 Protein Kinases, Compositions and Methods for Treating Prostate Cancer
WO2009064835A1 (en) 2007-11-16 2009-05-22 Incyte Corporation 4-pyrazolyl-n-arylpyrimidin-2-amines and 4-pyrazolyl-n-heteroarylpyrimidin-2-amines as janus kinase inhibitors
GB0723815D0 (en) 2007-12-05 2008-01-16 Glaxo Group Ltd Compounds
EP2231689B1 (en) * 2008-01-18 2016-07-20 Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic Novel cytostatic 7-deazapurine nucleosides
MY158994A (en) 2008-02-04 2016-11-30 Mercury Therapeutics Inc Ampk modulators
PE20091577A1 (es) 2008-03-03 2009-11-05 Novartis Ag Inhibidores de cinasa pim y metodos para su uso
BRPI0909040B8 (pt) * 2008-03-11 2021-05-25 Incyte Holdings Corp derivados de azetidina e ciclobutano, seus usos, e composição
KR101408517B1 (ko) 2008-03-21 2014-06-17 노파르티스 아게 신규한 헤테로시클릭 화합물 및 그의 용도
WO2009155156A1 (en) 2008-06-18 2009-12-23 Merck & Co., Inc. Inhibitors of janus kinases
KR102080429B1 (ko) 2008-06-26 2020-02-21 안테리오스, 인코퍼레이티드 경피 운반
TWI461423B (zh) 2008-07-02 2014-11-21 Astrazeneca Ab 用於治療Pim激酶相關病狀及疾病之噻唑啶二酮化合物
FR2933409B1 (fr) 2008-07-03 2010-08-27 Centre Nat Rech Scient NOUVEAUX PYRROLO °2,3-a! CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM
TWI496779B (zh) 2008-08-19 2015-08-21 Array Biopharma Inc 作為ｐｉｍ激酶抑制劑之三唑吡啶化合物
WO2010022081A1 (en) 2008-08-19 2010-02-25 Array Biopharma Inc. Triazolopyridine compounds as pim kinase inhibitors
BRPI0917459B1 (pt) 2008-08-20 2017-09-12 Zoetis Services Llc N-methyl-1- [trans-4- [methyl (7h-pyrrol [2,3-d] pyridol [2,3-d] pyrimidine compounds, use of these in therapy and crystalline a form of n-methyl- pyrimidin-4-yl) amino] cyclohexyl} methanosulphonamide
BRPI0918496A2 (pt) 2008-09-02 2019-09-24 Novartis Ag composto inibidor bicíclico de quinase, uso do mesmo, composição farmacêutica e método para inibir a atividade da quinase pim em uma célula
JP5584215B2 (ja) 2008-09-02 2014-09-03 ノバルティス アーゲー ヘテロ環ｐｉｍキナーゼ阻害剤
MX2011002365A (es) 2008-09-02 2011-04-04 Novartis Ag Derivados de picolinamida como inhibidres de cinasa.
CL2009001884A1 (es) * 2008-10-02 2010-05-14 Incyte Holdings Corp Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco.
US20110183958A1 (en) 2008-10-17 2011-07-28 Merck Frosst Canada Ltd. Azetidine derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase
JOP20190230A1 (ar) * 2009-01-15 2017-06-16 Incyte Corp طرق لاصلاح مثبطات انزيم jak و المركبات الوسيطة المتعلقة به
EP2210890A1 (en) 2009-01-19 2010-07-28 Almirall, S.A. Oxadiazole derivatives as S1P1 receptor agonists
US8263601B2 (en) 2009-02-27 2012-09-11 Concert Pharmaceuticals, Inc. Deuterium substituted xanthine derivatives
AU2010249443B2 (en) 2009-05-22 2015-08-13 Incyte Holdings Corporation 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]octane- or heptane-nitrile as JAK inhibitors
MY156727A (en) 2009-05-22 2016-03-15 Incyte Corp N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
UA110324C2 (en) 2009-07-02 2015-12-25 Genentech Inc Jak inhibitory compounds based on pyrazolo pyrimidine
EP2451813B1 (en) 2009-07-08 2014-10-01 Leo Pharma A/S Heterocyclic compounds as jak receptor and protein tyrosine kinase inhibitors
US20120157500A1 (en) 2009-08-24 2012-06-21 Weikang Tao Jak inhibition blocks rna interference associated toxicities
TW201111385A (en) 2009-08-27 2011-04-01 Biocryst Pharm Inc Heterocyclic compounds as janus kinase inhibitors
TW201113285A (en) * 2009-09-01 2011-04-16 Incyte Corp Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
SG10201405568UA (en) 2009-09-08 2014-11-27 Hoffmann La Roche 4-substituted pyridin-3-yl-carboxamide compounds and methods of use
EP2305660A1 (en) 2009-09-25 2011-04-06 Almirall, S.A. New thiadiazole derivatives
KR101921850B1 (ko) 2009-10-09 2018-11-23 인사이트 홀딩스 코포레이션 3-（4-（7Ｈ-피롤로〔2,3-ｄ〕피리미딘-4-일）-1Ｈ-피라졸-1-일）-3-사이클로펜틸프로판니트릴의 하이드록실, 케토 및 글루쿠로나이드 유도체
CA2775009A1 (en) 2009-10-20 2011-04-28 Cellzome Limited Heterocyclyl pyrazolopyrimidine analogues as jak inhibitors
US8671402B2 (en) 2009-11-09 2014-03-11 Bank Of America Corporation Network-enhanced control of software updates received via removable computer-readable medium
EP2332917B1 (en) 2009-11-11 2012-08-01 Sygnis Bioscience GmbH & Co. KG Compounds for PIM kinase inhibition and for treating malignancy
EP2504030A4 (en) 2009-11-24 2013-06-26 Alderbio Holdings Llc IL-6 ANTAGONISTS FOR INCREASING ALBUMIN AND / OR REDUCING CRP
EP2506852A4 (en) 2009-12-04 2013-06-19 Univ Texas INTERFERONTHERAPIES IN COMBINATION WITH BLOCKING OF STAT3 ACTIVATION
ES2461967T3 (es) 2009-12-18 2014-05-21 Pfizer Inc. Compuestos de pirrolo[2,3-d]pirimidina
CN102712640A (zh) 2010-01-12 2012-10-03 弗·哈夫曼-拉罗切有限公司 三环杂环化合物、其组合物和应用方法
SA111320200B1 (ar) 2010-02-17 2014-02-16 ديبيوفارم اس ايه مركبات ثنائية الحلقة واستخداماتها كمثبطات c-src/jak مزدوجة
CA2790070C (en) 2010-02-18 2018-03-06 Incyte Corporation Cyclobutane and methylcyclobutane derivatives as janus kinase inhibitors
AU2011224484A1 (en) 2010-03-10 2012-09-27 Incyte Holdings Corporation Piperidin-4-yl azetidine derivatives as JAK1 inhibitors
US8962596B2 (en) 2010-04-14 2015-02-24 Array Biopharma Inc. 5,7-substituted-imidazo[1,2-C]pyrimidines as inhibitors of JAK kinases
EP2390252A1 (en) 2010-05-19 2011-11-30 Almirall, S.A. New pyrazole derivatives
MY161078A (en) 2010-05-21 2017-04-14 Incyte Holdings Corp Topical formulation for a jak inhibitor
US8637529B2 (en) 2010-06-11 2014-01-28 AbbYie Inc. Pyrazolo[3,4-d]pyrimidine compounds
WO2012003457A1 (en) 2010-07-01 2012-01-05 Mtm Research Llc Anti-fibroblastic fluorochemical emulsion therapies
WO2012045010A1 (en) 2010-09-30 2012-04-05 Portola Pharmaceuticals, Inc. Combinations of 4-(3-(2h-1,2,3-triazo-2-yl) phenylamino)-2-((1r,2s)-2-aminocyclohexylamino) pyrimidine-5-carboxamide and fludarabine
WO2012068440A1 (en) 2010-11-19 2012-05-24 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors
EP2640723A1 (en) 2010-11-19 2013-09-25 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
SG190950A1 (en) 2010-12-03 2013-07-31 Ym Biosciences Australia Pty Treatment of jak2-mediated conditions
ES2547916T3 (es) * 2011-02-18 2015-10-09 Novartis Pharma Ag Terapia de combinación de inhibidores de mTOR/JAK
CN102247368B (zh) 2011-05-19 2013-05-29 安徽永生堂药业有限责任公司 一种复方阿伐斯汀缓释片及其制备方法
CN102218042A (zh) 2011-05-26 2011-10-19 青岛黄海制药有限责任公司 富马酸喹硫平组合物的缓释片剂及其制备方法
KR20140040819A (ko) 2011-06-20 2014-04-03 인사이트 코포레이션 Ｊａｋ 저해제로서의 아제티디닐 페닐, 피리딜 또는 피라지닐 카르복스아미드 유도체
WO2013007765A1 (en) 2011-07-13 2013-01-17 F. Hoffmann-La Roche Ag Fused tricyclic compounds for use as inhibitors of janus kinases
WO2013007768A1 (en) 2011-07-13 2013-01-17 F. Hoffmann-La Roche Ag Tricyclic heterocyclic compounds, compositions and methods of use thereof as jak inhibitors
HK1198579A1 (en) 2011-08-10 2015-04-30 Novartis Pharma Ag Jak p13k/mtor combination therapy
TW201313721A (zh) 2011-08-18 2013-04-01 Incyte Corp 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物
UA111854C2 (uk) * 2011-09-07 2016-06-24 Інсайт Холдінгс Корпорейшн Способи і проміжні сполуки для отримання інгібіторів jak
WO2013173720A1 (en) 2012-05-18 2013-11-21 Incyte Corporation Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
US10155987B2 (en) 2012-06-12 2018-12-18 Dana-Farber Cancer Institute, Inc. Methods of predicting resistance to JAK inhibitor therapy
EA201492287A1 (ru) 2012-06-15 2015-07-30 Консерт Фармасьютикалс, Инк. Дейтерированные производные руксолитиниба
WO2014016396A1 (en) 2012-07-27 2014-01-30 Ratiopharm Gmbh Oral dosage forms for modified release comprising ruxolitinib
CN102772384A (zh) 2012-08-07 2012-11-14 四川百利药业有限责任公司 一种盐酸米诺环素缓释片及其制备方法
WO2014036016A1 (en) 2012-08-31 2014-03-06 Principia Biopharma Inc. Benzimidazole derivatives as itk inhibitors
UA117572C2 (uk) 2012-11-01 2018-08-27 Інсайт Холдинґс Корпорейшн Трициклічні конденсовані похідні тіофену як інгібітори jak
PH12020551186B1 (en) 2012-11-15 2024-03-20 Incyte Holdings Corp Sustained-release dosage forms of ruxolitinib
JP6397831B2 (ja) 2013-03-06 2018-09-26 インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ Ｊａｋ阻害剤の製造方法及びその中間体
TWI719401B (zh) 2013-05-17 2021-02-21 美商英塞特公司 作為jak抑制劑之聯吡唑衍生物
KR20160045081A (ko) 2013-08-07 2016-04-26 인사이트 코포레이션 Jak1 억제제용 지속 방출 복용 형태
TW201529074A (zh) 2013-08-20 2015-08-01 Incyte Corp 在ｃ-反應蛋白含量較高之實體腫瘤患者中的存活益處
CN106456773A (zh) 2014-02-28 2017-02-22 因赛特公司 用于治疗骨髓增生异常综合征的jak1抑制剂
LT3129021T (lt) 2014-04-08 2020-12-10 Incyte Corporation B ląstelių piktybiškumo gydymas jak ir pi3k inhibitorių deriniu
MX2016014192A (es) 2014-04-30 2017-05-01 Incyte Corp Procesos para preparar un inhibidor de cinasas de janus 1 (jak1) y nuevas formas de este.
WO2015184087A2 (en) 2014-05-28 2015-12-03 Institute For Myeloma & Bone Cancer Research Anti-cancer effects of jak2 inhibitors in combination with thalidomide derivatives and glucocorticoids
WO2015184305A1 (en) 2014-05-30 2015-12-03 Incyte Corporation TREATMENT OF CHRONIC NEUTROPHILIC LEUKEMIA (CNL) AND ATYPICAL CHRONIC MYELOID LEUKEMIA (aCML) BY INHIBITORS OF JAK1
US10766900B2 (en) 2017-12-29 2020-09-08 Formosa Laboratories, Inc. Baricitinib intermediate, method for forming Baricitinib intermediate, and method for preparing Baricitinib or pharmaceutically acceptable salt thereof
AU2020219797B2 (en) 2019-02-06 2025-10-16 Sun Pharmaceutical Industries, Inc. Process for preparing enantiomerically enriched jak inhibitors

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