中文摘要：本发明公开了一种不依赖于TLR的佐剂化合物，其结构由所述的组合1，或者该组合的药用盐组成；所述的组合物包括X， Y， Z， n， R1， R2， R3， R4和W；本发明还公开了该佐剂、以该佐剂为成分的药用化合物的制备方法和作用。
外文摘要：A TLR-independent adjuvant compound that corresponds in structure to Formula I, below, or its pharmaceutically acceptable salt is disclosed in which X, Y, Z, n, R1, R2, R3, R4 and W are defined within. Also disclosed are a method of its preparation and use, as well as a pharmaceutical composition containing the same.
NOVELTY - Substituted 4-carbamoylphenylcarbamoyl compounds (I) are new.
USE - The compounds (I) are useful as adjuvants for vaccination (claimed) and useful in the prevention of premature death by infections and for inducing the secretion of TNF- alpha . The ability of (I) to induce TNF- alpha was tested in THP-1 cells. The results showed that the cells treated with N-(4-(3-chlorophenethylcarbamoyl)-2-(4-hydroxyphenethoxy)phenyl)benzofuran-2-carboxamide exhibited TNF- alpha levels of 2477 pg/ml.
ADVANTAGE - The compounds (I): are TLR-independent adjuvants; do not exhibit the toxicity of lipopolysaccharide while exhibiting activation of many similar cellular signaling pathways; are easy to prepare; and exhibit robust and dose-dependent adjuvant activity.
主权项：Substituted 4-carbamoylphenylcarbamoyl compounds of formula (I) and their salts are new.
X1 = O, S, NR5 or -CH2;
R5 = hydrido or 1-4C hydrocarbyl;
Y 1 = O, CH2, or absent;
Z1 = O, S, NR6 or CH2;
R6 = hydrido or 1-4C hydrocarbyl;
n = 0-2, where n is only zero when Z1 is -CH2; either
R1, R2 = H or OH, where at least one of R1 and R2 is OH;
R3, R4 = hydrido, halo, azido, 1-4C hydrocarbyl, 1-4C hydrocarbyloxy or trifluoromethyl; and
W1 = 5-12-membered ring structure containing one or two rings that optionally contain 1-4 heteroatoms comprising O, N or S, and 1-3 substituents comprising hydrido, OH, 1-4C hydrocarbyl, 1-4C hydrocarbyloxy, halo and trifluoromethyl bonded to at least one ring atom.
An INDEPENDENT CLAIM is also included for an improved method of vaccination, comprising contacting mammalian cells with an immunizing composition that comprises an immunogen and adjuvant.
 
申请号：WO2015US43830
公开/公告号：WO2016022700A2
申请日：2015-08-05
公开/公告日：2016-02-11
申请/专利权人：SCRIPPS RESEARCH INST; UNIV TEXAS SYSTEM AUSTIN BOARD OF REGENTS
发明/设计人：BOGER DALE L; BEUTLER BRUCE
分类号：C07D209/18; C07D307/85; C07D403/12; C07D405/12; C07D409/12
主分类号：A61K31/343; A61K31/404; C07D209/04; C07D209/12; C07D307/78
法律状态：公开发明
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