发明名称 SYNTHESIS OF RESORCYLIC ACID LACTONES USEFUL AS THERAPEUTIC AGENTS
摘要 Disclosed are macrocyclic compounds of formulae I, I′, II, II′, III, III′, IV, and V, which are analogs of the pochonin resorcylic acid lactones, pharmaceutical compositions comprising the compounds, and methods and uses comprising the compounds for the treatment of diseases mediated by kinases and Heat Shock Protein 90 HSP90.
申请公布号 US2016075677(A1) 申请公布日期 2016.03.17
申请号 US201514691880 申请日期 2015.04.21
申请人 Winssinger Nicolas;Barluenga Sofia;Karplus Martin 发明人 Winssinger Nicolas;Barluenga Sofia;Karplus Martin
分类号 C07D313/00;A61K31/5377;A61K31/496;A61K31/365;A61K31/454;A61K31/4025;C07D405/12;A61K31/541;C07D405/14;A61K31/4523;C07D225/06 主分类号 C07D313/00
代理机构 代理人
主权项 1. A compound of formula I or I′, or a tautomer thereof, a pharmaceutically acceptable salt, solvate, ester or prodrug thereof:wherein: X is O, S or NR; Y is —OR, —O—(CH2)mCOOR, —O—(CH2)mCON(R)2, —N(R)2, —N(R)SOR or —N(R)SO2R, wherein the groups bound to the nitrogen atom may be in Z- or E-configuration; R1 and R2 are independently hydrogen, halogen, OR, N(R)2, SR, azido, nitro, cyano, aliphatic, aryl, alkylaryl, arylalkyl, heterocyclyl, heteroaryl, —S(O)R, —S(O)2R, —SO2N(R)2, —N(R)SO2R, —N(CO)R, —N(CO)N(R)2, —N(CO)OR, —O(CO)R, —(CO)R, —(CO)OR, —(CO)N(R)2, —O(CO)OR, or —O(CO)N(R)2; R3, R4, R5, R6, R7, R8, R9 and R10 are independently hydrogen, halogen, azido, nitro, cyano, aliphatic, alkylaryl, aralkyl, aryl, heteroalkyl, alkylheteroaryl, heterocyclyl, heteroaryl, OR, N(R)2, SR, —O(CH2)mN(R)C(O)(CH2)pR, —O(CH2)mOC(O)(CH2)pR, —O(CH2)mC(O)(CH2)pN(R)2, —O(CH2)mC(O)(CH2)pOR, —O(CH2)mN(R)C(O)(CH2)pOR, —O(CH2)mN(R)C(O)(CH2)pN(R)2, —O(CH2)mOC(O)(CH2)pOR, —O(CH2)mOC(O)(CH2)pN(R)2, —NR(CH2)mN(R)C(O)(CH2)pR, —NR(CH2)mOC(O)(CH2)pR, —NR(CH2)mC(O)(CH2)pN(R)2, —NR(CH2)mC(O)(CH2)pOR, —NR(CH2)mN(R)C(O)(CH2)pOR, —NR(CH2)mN(R)C(O)(CH2)pN(R)2, —NR(CH2)mOC(O)(CH2)pOR, —NR(CH2)mOC(O)(CH2)pN(R)2, —(CH2)mN(R)C(O)CH2)R, —(CH2)mOC(O)(CH2)pR, —(CH2)mC(O)(CH2)pN(R)2, —(CH2)mC(O)(CH2)pOR, —(CH2)mN(R)C(O)(CH2)pOR, —(CH2)mN(R)C(O)(CH2)pN(R)2, —(CH2)mOC(O)(CH2)pOR, —(CH2)mOC(O)(CH2)pN(R)2, —(CH2)mN3, —O(CH2)mN3—(CH2)mN(R)2, —(CH2)mOR, —(CH2)mS(O)(CH2)pR, —(CH2)mS(O)2(CH2)pR, —(CH2)mSO2(CH2)pN(R)2, or —(CH2)mN(R)SO2(CH2)pR; and each R is independently R11, hydrogen, aliphatic, amino, azido, cyano, nitro, alkylamino, dialkylamino, OH, alkoxy, carbonylamino, aminocarbonyl, alkoxycarbonyl, carbonyloxy, carboxy, acyl, aryl, alkaryl, arylalkyl including benzyl, heteroalkyl, heteroaryl, heterocyclyl, or a protecting group; or two R on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclic or heteroaryl ring; wherein where a group contains more than one R substituent; wherein R is optionally substituted, and each R can be the same or different; R11 is the group:where Z is an inorganic or organic counterion; n is 0, 1 or 2; m and p are independently 0, 1, 2, 3, 4 or 5; and the dashed lines indicate either a single or a double bond, where the valence requirements are fulfilled by additional hydrogen atoms; and wherein in formula I′, when n is 1, and X is O and a double bond is present between the carbon atoms bearing R9 and R10, then at least one of R5, R6, R7, R8, R9 or R10 is not hydrogen; and wherein in formula I′, when n is 1 and X is O and the bond between the carbon atoms bearing R9 and R10 is a single bond, then at least one of R5, R6, R7 or R8 is not hydrogen.
地址 Strasbourg FR
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