发明名称 Opsin-Binding Ligands, Compositions and Methods of Use
摘要 Compounds and compositions of said compounds along with methods of use of compounds are disclosed for treating ophthalmic conditions related to mislocalization of opsin proteins, the misfolding of mutant opsin proteins and the production of toxic visual cycle products that accumulate in the eye. Compounds and compositions useful in the these methods, either alone or in combination with other therapeutic agents, are also described.
申请公布号 US2017037018(A1) 申请公布日期 2017.02.09
申请号 US201615204577 申请日期 2016.07.07
申请人 BIKAM PHARMACEUTICALS INC. 发明人 Garvey David S.;LaRosa Gregory J.;Greenwood Jeremy R.;Brewer Mark L.;Quach Tan;Cöté Jamie B.;Berman Judd
分类号 C07D295/215;C07D295/185;C07D295/205;C07D295/26;C07D207/12;C07D241/04;C07B59/00;C07D211/38;C07D241/08;C07D205/04;C07C275/14;C07C233/10;C07D207/14 主分类号 C07D295/215
代理机构 代理人
主权项 1. A compound having the structure of Formula I A-B-Q-V   Formula I wherein A is: B is —(CH2)n—, —CH═CH—, —CH2—N(R22)—, —CH2—O—, —C(O)—CH2—C(O)—,or —C(O)NR22—, wherein n=0, 1 or 2; E is —N(R22)— or oxygen; Q is —C(O)—, —(CH2)a—, —S(O2)— or —CH2—C(O)—, wherein a is 1 or 2; V is NR21R22, wherein b is 1 or 2 and a is 1 or 2; Y is NR22, N-Q-U, CR22R23, oxygen, S(O)n, N—C(S)—NR22R23, N—(C═N—CN)—NR22R23, N—(C═N—SO2CH3)—NR22R23, C═NOR22, C═N—NR22R23 or CH-Q-U, n is 0, 1 or 2; U is NR22R23, lower alkyl, haloalkyl, alkoxy, OR22 or hydrogen; X is hydrogen, alkyl, or —C≡CR9; R1 and R2 are independently —CH3 or —CH2CH3; R3 is hydrogen, —CH3 or —CH2CH3; Ra and Rb, are each independently hydrogen, deuterium or —CH3—; Rc and Rd, are each independently hydrogen, alkoxy, lower alkyl or alkenyl; R4 is —CH3, —CF3, —C2H5 or —C3H5; R5, R6 and R7 are each independently hydrogen, lower alkyl, halogen, dialkylamine, nitro or dialkylamine; Z is CR3, CH or nitrogen; R8 is —CH2— or —C(O)—; R9, R14 and R16 are each independently hydrogen, or —CH3; R10 is N—R13, sulfur or oxygen; R11 is ═N—, or ═C(CH3)—; R12 is lower alkyl, alkoxy or haloalkyl; R13 is phenyl, lower alkyl or haloalkyl; R15 is hydrogen or —C(O)CH3; R17 and R18 together are —(CH2)4— or —CH═CH—CH═CH—; R19 and R20 together are —CH2-C(CH3)2-CH2-C(O)— or —CH═CH—CH═CH—; R21 is hydrogen, —C(O)CH3, —CH3 or —CH2CH3; R22 and R23 are each independently hydrogen or lower alkyl; R24 and R25 are each independently hydrogen or —CH3; R26 is NR22R23 or alkoxy; or wherein R1 and R2 taken together or Ra and Rb taken together along with the carbon to which they are attached are cyclopropyl; or R24 and R25 taken together along with the two carbons to which they are attached are cyclopropyl; or R24 and R25 taken together is oxo; T is oxygen, —N(R16)— or sulfur; and E is oxygen, —N(R16)—, sulfur or —C(O)—; including pharmaceutically acceptable salts, solvates and hydrates thereof.
地址 Cambridge MA US