发明名称 TYK2 INHIBITORS AND USES THEREOF
摘要 The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
申请公布号 US2017066763(A1) 申请公布日期 2017.03.09
申请号 US201615254071 申请日期 2016.09.01
申请人 Nimbus Lakshmi, Inc. 发明人 Masse Craig E.;Greenwood Jeremy Robert;Romero Donna L.;Harriman Geraldine C.;Wester Ronald T.;Shelley Mee;Kennedy-Smith Joshua Jahmil;Dahlgren Markus;Mondal Sayan
分类号 C07D471/04;C07D519/00 主分类号 C07D471/04
代理机构 代理人
主权项 1. A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein: each of X and Y is independently ═C(R6)— or ═N—; Ring A is phenyl; a 5-6 membered partially unsaturated monocyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 6-12 membered partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7-12 membered bicyclic heteroaryl ring having 2-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of R1 and R1′ is independently hydrogen, —R2, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, or —N(R)S(O)2R; or R1 and R1′ are taken together with their intervening atoms to form an optionally substituted 3-7 membered spiro-fused ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each R2 is independently an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R3 is C2-6 aliphatic or Cy1; wherein R3 is substituted with n instances of R8; R5 is halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)S(O)2R, and Cy2; wherein R5 is substituted with p instances of R9; or when Ring A is partially unsaturated, L1R5, taken together, may also be absent; each of Cy1 and Cy2 is independently phenyl; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 6-12 membered bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 6-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each instance of R6 is independently hydrogen, —R2, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, or —N(R)S(O)2R; each instance of R7 and R8 is independently oxo, —R2, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, or —N(R)S(O)2R; each instance of R9 is independently oxo, C1-6 hydroxyaliphatic, —R2, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, or —N(R)S(O)2R; L1 is a covalent bond or a C1-6 bivalent saturated or unsaturated, straight or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by —N(R)—, —N(R)C(O)—, —C(O)N(R)—, —N(R)S(O)2—, —S(O)2N(R)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)— or —S(O)2—; m is 0-2; n is 0-4; p is 0-3; and each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur.
地址 Cambridge MA US