发明名称 Compositions and methods for inhibition of the JAK pathway
摘要 The invention encompasses compounds having formula I-V and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK3, may be therapeutically useful.
申请公布号 US8815848(B2) 申请公布日期 2014.08.26
申请号 US201313750632 申请日期 2013.01.25
申请人 Rigel Pharmaceuticals, Inc. 发明人 Li Hui;Thota Sambaiah;Carroll David;Argade Ankush;Tso Kin;Sran Arvinder;Clough Jeffrey;Keim Holger;Bhamidipati Somasekhar;Taylor Vanessa;Cooper Robin;Singh Rajinder;Wong Brian
分类号 C07D239/48;C07D285/22;A61K31/506 主分类号 C07D239/48
代理机构 Klarquist Sparkman, LLP 代理人 Young Travis;Klarquist Sparkman, LLP
主权项 1. A compound of formula IIor a pharmaceutically acceptable salt thereof, wherein: X is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halo, nitro, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl; R is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl and substituted cycloalkyl; ring A is phenyl; Y is selected from the group consisting of a bond, —NR7—, —C(O)NR7—, —NR7C(O)—, —NR7C(O)O—, —OC(O)NR7—, —NR7C(O)NR7—, oxygen and sulfur, where R7 is independently hydrogen, alkyl or substituted alkyl; alk is a bond or a straight or branched chain alkylene group, wherein when alk and Y each are a bond then R1 is attached to ring A by a single covalent bond; R1 is selected from the group consisting of cyano, acylamino, aminoacyl, aryl, substituted aryl, carboxyl, carboxyl ester, carboxyl ester oxy, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, acyl, aminoacyloxy, and aminocarbonylamino; or R1-alk-Y— is R10—C(O)—S-alk-C(O)—, wherein alk is as defined herein and R10 is alkyl or substituted alkyl; orR1-alk-Y— is R11R12NS(O)2—, wherein R11 and R12 independently are alkyl or substituted alkyl; p is 0, 1, 2 or 3; each R2 independently is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, aryloxy, substituted aryloxy, cycloalkyl, substituted cycloalkyl, cycloalkoxy, substituted cycloalkoxy, heteroaryloxy, substituted heteroaryloxy, heterocyclyloxy, substituted heterocyclyloxy, nitro, and halo; Z1, Z2, and Z3 are carbon; q is 1, 2 or 3; each R3 independently is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, cycloalkyl or substituted cycloalkyl, halo, heterocyclic and substituted heterocyclic; R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, acyl and M+, wherein M+is a metal counterion selected from the group consisting of K+, Na+, Li+, or +N(R6)4, wherein R6 is hydrogen or alkyl, and the nitrogen of SO2NR4W is N−, a divalent counterion selected from the group consisting of Ca2+, Mg2+, and Ba2+, and the nitrogen of SO2NR4W is N−; W is selected from the group consisting of C1-C3 alkylene, substituted C1-C3 alkylene, C2-C3 alkenylene and substituted C2-C3 alkenylene wherein one or more of the carbon atoms have been replaced with a moiety selected from oxygen, sulfur, S(O), S(O)2, C(O), or NR8 where R8 is selected from the group consisting of hydrogen and alkyl or is a bond participating in a —N═C< site of unsaturation.
地址 South San Francisco CA US