发明名称 Compounds (cystein based lipopeptides) and compositions as TLR2 agonists used for treating infections, inflammations, respiratory diseases etc
摘要 The invention provides a novel class of compounds viz. generally lipopeptides like Pam3CSK4, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 2. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness a vaccine.
申请公布号 US8808703(B2) 申请公布日期 2014.08.19
申请号 US201113636328 申请日期 2011.03.23
申请人 发明人 Wu Tom Yao-Hsiang;Zou Yefen;Hoffman Timothy Z.;Pan Jianfeng
分类号 A61K49/00;A61K39/385;A61K39/12;A61K39/02;A61K45/00 主分类号 A61K49/00
代理机构 Genomics Institute of the Novartis Research Foundation 代理人 Raymond Daniel E.;Genomics Institute of the Novartis Research Foundation
主权项 1. A compound of Formula (I), or pharmaceutically acceptable salt thereof: wherein: R1 is H, —C(O)—C7-C18alkyl or —C(O)—C1-C6alkyl;R2 is C7-C18alkyl;R3 is C7-C18alkyl;L1 is —CH2O—, —CH2NR7C(O)— or —CH2OC(O)NR7—;L2 is —O—, —NR7C(O)— or —OC(O)NR7—;R4 is -L3R5 or -L4R5;R5 is —N(R7)2, -OR7, —P(O)(OR7)2, —C(O)OR7, —NR7C(O)L3R8, —NR7C(O)L4R8, —OL3R6, —C(O)NR7L3R8, —C(O)NR7L4R8, —S(O)20R7, —OS(O)2OR7, C1-C6alkyl, a C6aryl, a C10aryl, a C14aryl, 5 to 14 ring membered heteroaryl containing 1 to 3 heteroatoms selected from O, S and N, C3-C8cycloalkyl or a 5 to 6 ring membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O, S and N, wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R5 are each unsubstituted or the aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R5 are each substituted with 1 to 3 substituents independently selected from —OR9, —OL3R6, —OL4R6, —OR7, and —C(O)OR7;L3 is a C1-C10alkylene, substituted with 1 to 4 R6 groups, or the C1-C10alkylene of L3 is substituted with 2 C1-C6alkyl groups on the same carbon atom which together, along with the carbon atom they are attached to, form a C3-C8cycloakyl;L4 is —((CR7R7)pO)q(CR10R10)p— or —(CR11R11)((CR7R7)pO)q((CR10R10)p—, wherein each R11 is a C1-C6alkyl groups which together, along with the carbon atom they are attached to, form a C3-C8cycloakyl;each R6 is independently selected from halo, C1-C6alkyl, C1-C6alkyl substituted with 1-2 hydroxyl groups, —OR7, —N(R7)2, —C(O)N(R7)2, —P(O)(OR7)2, a C6aryl, a C10aryl and a C14aryl;each R7 is independently selected from H and C1-C6alkyl;R8 is selected from —SR7, —C(O)OH, —P(O)(OR7)2, and a 5 to 6 ring membered heterocycloalkyl containing 1 to 3 heteroatoms selected from O and N;R9 is phenyl;each R10 is independently selected from H and halo;each p is independently selected from 1, 2, 3, 4, 5 and 6, andq is 1, 2, 3 or 4.
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