发明名称 Aminoglycoside antibiotics with reduced ototoxicity
摘要 This disclosure relates generally to aminoglycoside derivatives of Formula (I) as described herein. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating bacterial infections by administering these compounds and pharmaceutical compositions to subjects in need thereof.
申请公布号 US9238670(B2) 申请公布日期 2016.01.19
申请号 US201414212964 申请日期 2014.03.14
申请人 The Board of Trustees of the Leland Stanford Junior University 发明人 Ricci Anthony J.;Greenhouse Robert J.;Cheng Alan G.
分类号 A61K31/70;C07H15/236;C07D407/12 主分类号 A61K31/70
代理机构 Mintz Levin Cohn Ferris Glovsky and Popeo, P.C. 代理人 Mintz Levin Cohn Ferris Glovsky and Popeo, P.C. ;Ashraf, J.D. Shovon
主权项 1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:wherein the bond is a single bond or double bond; each of R11 and R12 independently is H, C(O)Ra, C(O)ORa, C(O)NHRa, C(O)NRaRb, or S(O)nRa, in which n is 1, or 2, and each of Ra and Rb, independently is C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 12-membered heterocycloalkyl, or 5 to 14-membered heteroaryl; or Ra and Rb, together with the N atom to which they are attached, form a 4 to 12-membered heterocycloalkyl ring having 0 or 1 additional heteroatom; and each of Ra, Rb, and the 4 to 12-membered heterocycloalkyl ring formed by Ra and Rb, is optionally substituted; each of R21, R22, R23, and R24, independently, is H or optionally substituted C1-C6 alkyl; each of R31 and R32, independently, is H or OH; R41 is H or CH2OH; and each of R51 and R52, independently, is OH, NH2, unsubstituted mono-C1-C6 alkylamino, or unsubstituted di-C1-C6 alkylamino, provided that at least one of R11 and R12 is not H; further when R12 is C(O)Ra or S(O)2Ra, then (i) Ra is not alkyl substituted with NH2 or (ii) Ra is unsubstituted alkyl or alkyl substituted with one or more -Q-T, wherein Q is a bond or C1-C3 alkyl linker each optionally substituted with halo, cyano, hydroxyl or C1-C6 alkoxy, and T is H, halo, cyano, —ORc, —C(O)Rc, —C(O)ORc, —C(O)NRcRd, —NRdC(O)Rc, —NRdC(O)ORc, —S(O)2Rc, —S(O)2NRcRd, RS1, —NHRS1, or —N(RS1)2, in which each of Rc and Rd, independently is H or RS2, each of RS1 and RS2, independently, is C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 4 to 12-membered heterocycloalkyl, or 5- or 6-membered heteroaryl; or Rc and Rd, together with the N atom to which they are attached, form a 4 to 12-membered heterocycloalkyl ring having 0 or 1 additional heteroatom or 5 to 14-membered heteroaryl.
地址 Palo Alto CA US