发明名称 Kinase inhibitors and their uses
摘要 The present disclosure provides compounds that inhibit protein kinases, such as JAK, Axl, or Syk kinases, compositions comprising the compounds and methods of using the compounds to inhibit protein kinase and treat and/or prevent diseases associated with inappropriate kinase activity.
申请公布号 US9096542(B2) 申请公布日期 2015.08.04
申请号 US201113242994 申请日期 2011.09.23
申请人 Rigel Pharmaceuticals, Inc. 发明人 Ding Pingyu;Argade Ankush;Goff Dane;Singh Rajinder;Masuda Esteban;Taylor Vanessa;Holland Sacha
分类号 C07D495/04;C07D495/12;A61K31/519;C07D239/94;C07D239/95;C07D473/16;C07D487/04;A61P19/02;A61P35/00 主分类号 C07D495/04
代理机构 McDonnell Boehnen Hulbert & Berghoff LLP 代理人 Young Travis;McDonnell Boehnen Hulbert & Berghoff LLP
主权项 1. A compound according to structural formula (I): or a salt or N-oxide thereof, wherein: B is R2 is selected from the group consisting of a (C6-C20) aryl optionally substituted with one or more R8, a 5-20 membered heteroaryl optionally substituted with one or more R8, a (C7-C28) arylalkyl optionally substituted with one or more R8 and a 6-28 membered heteroarylalkyl optionally substituted with one or more R8; R4 is a saturated or unsaturated, bridged or unbridged cycloalkyl containing a total of from 3 to 16 annular carbon atoms that is substituted with an R7 group, with the proviso that when R4 is an unsaturated unbridged cycloalkyl, or a saturated bridged cycloalkyl, this R7 substituent is optional, wherein R4 is further optionally substituted with one or more Rf R7 is selected from the group consisting of —C(O)ORd, —C(O)NRdRd, —C(O)NRdORd, or —C(O)NRdNRdRd; each R8 group is, independently of the others, selected from the group consisting of a water-solubilizing group, Ra, Rb, C1-C8 alkyl optionally substituted with one or more Ra and/or Rb, C3-C8 cycloalkyl optionally substituted with one or more Ra and/or Rb, heterocycloalkyl containing 3 to 12 annular atoms, optionally substituted with one or more Ra and/or Rb, C1-C8 alkoxy optionally substituted with one or more Ra and/or Rb, and —O—(CH2)x—Rb, where x is 1-6; each Ra is, independently of the others, selected from the group consisting of hydrogen, C1-C8 alkyl, bridged or unbridged C3-C10 cycloalkyl, bridged or unbridged heterocycloalkyl containing 3 to 12 annular atoms, heteroaryl, (C6-C14) aryl, and (C7-C20) arylalkyl, wherein Ra is optionally substituted with one or more Rf; each Rb is, independently of the others, a group selected from the group consisting of ═O, —ORa, (C1-C3) haloalkyloxy, ═S, —SRa, ═NRa, ═NORa, —NRcRc, halogen, —C1-C3haloalkyl, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Ra, —S(O)2Ra, —S(O)2ORa, —S(O)NRcRc, —S(O)2NRcRc, —OS(O)Ra, —OS(O)2Ra, —OS(O)2ORa, —OS(O)2NRcRc, —C(O)Ra, —C(O)ORa, —C(O)NRcRc, —C(O)NRaORa, —C(NH)NRcRc, —C(NRa)NRcRc, —C(NOH)Ra, —C(NOH)NRcRc, —OC(O)Ra, —OC(O)ORa, —OC(O)NRcRc, —OC(NH)NRcRc and —OC(NRa)NRcRc; each Rc is, independently of the others, is Ra or two Rc that are bonded to the same nitrogen atom taken together with the nitrogen atom to which they are both attached form a heterocycloalkyl group containing 5 to 8 annular atoms, which optionally includes from 1 to 3 additional heteroatomic groups selected from the group consisting of —O—, —S—, —N(—(CH2)y—Ra)—, —N(—(CH2)y—C(O)Ra)—, —N(—(CH2)y—C(O)ORa)—, —N(—(CH2)y—S(O)2Ra)—, —N(—(CH2)y—S(O)2ORa)— and —N(—(CH2)y—C(O)NRaR1)—, where y is 0-6, wherein the heterocycloalkyl is optionally substituted with one or more Rf; each Rd is, independently of the others, selected from the group consisting of Ra, and Rc; and each Rf is independently —C1-C8 alkoxy, —C1-C8 alkyl, —C1-C6 haloalkyl, cyano, nitro, amino, (C1-C8 alkyl)amino, di(C1-C8 alkyl)amino, phenyl, benzyl, oxo, or halogen, or any two Rf bonded to adjacent atoms, taken together with the atoms to which they are each attached, form a fused saturated or unsaturated cycloalkyl or a fused saturated or unsaturated heterocycloalkyl group containing 5 to 8 annular atoms, wherein the formed cycloalkyl and heterocycloalkyl groups are optionally substituted with one or more groups which are each independently selected from halogen, C1-C8 alkyl, and phenyl.
地址 South San Francisco CA US