公开(公告)号：KR100847448B1

公开(公告)日：2008-07-21

申请号：KR1020070028181

申请日：2007-03-22

Applicant: 한국화학연구원

Inventor： 안미자 ,  정명희 ,  조남옥 ,  이병호

IPC: C07D271/06 ,  C07D413/06 ,  A61K31/535 ,  A61P3/04

Abstract: 3-Aryl-5-alkyl-1,2,4-oxadiazole derivatives are provided to reduce eating by competing with MCH R1(melanin-concentrating hormone receptor subtype-1) associated with obesity, so that the compounds are useful for preventing or treating obesity. The 3-aryl-5-alkyl-1,2,4-oxadiazole derivatives represented by the formula(1) are useful as antagonist of MCH R1, wherein R1 is (C3-C5) branched alkyl, (C1-C3)dialkylamino(C1-C3)alkyl or (C1-C3) linear alkyl which is optionally substituted by pyridine, piperidine or (C5-C7) cycloalkyl; R2 is halogen-substituted phenyl, CF3-substituted phenyl, phenyl substituted by phenoxy which is optionally substituted by halogen or (benzo[1,3]dioxol-5-yl)phenyl; and X is -NHCO or -NHCONH-. A method for preparing the 3-aryl-5-alkyl-1,2,4-oxadiazole derivatives represented by the formula(1a) comprises the steps of: (1) reacting 4-aminobenzonitrile represented by the formula(2) with organic acid(R2COOH) in the presence of solvent and binding reagent to prepare amide compounds represented by the formula(3); (2) reacting the amide compounds represented by the formula(3) with hydroxylamine hydrochloride in the presence of solvent to prepare amidoxime represented by the formula(4); and (3) reacting the amidoxime represented by the formula(4) with another organic acid(R1COOH) in the presence of solvent and binding reagent to prepare 1,2,4-oxadiazole ring.

Abstract translation: 提供3-芳基-5-烷基-1,2,4-恶二唑衍生物以通过与与肥胖相关的MCH R1（黑色素浓缩激素受体亚型-1）竞争来减少进食，使得该化合物可用于预防或治疗 肥胖。 由式（1）表示的3-芳基-5-烷基-1,2,4-恶二唑衍生物可用作MCH R 1的拮抗剂，其中R 1是（C 3 -C 5）支链烷基，（C 1 -C 3）二烷基氨基（ C1-C3）烷基或任选被吡啶，哌啶或（C5-C7）环烷基取代的（C1-C3）直链烷基; R 2是卤素取代的苯基，CF 3取代的苯基，被苯氧基取代的苯基，其被卤素或（苯并[1,3]二氧杂环戊烯-5-基）苯基任选取代; X是-NHCO或-NHCONH-。 制备由式（1a）表示的3-芳基-5-烷基-1,2,4-恶二唑衍生物的方法包括以下步骤：（1）使由式（2）表示的4-氨基苄腈与有机酸 （R2COOH）在溶剂和结合试剂存在下反应制备式（3）表示的酰胺化合物。 （2）在溶剂存在下使式（3）表示的酰胺化合物与羟胺盐酸盐反应，制备由式（4）表示的偕胺肟; 和（3）在溶剂和结合试剂的存在下使由式（4）表示的偕胺肟与另一种有机酸（R1COOH）反应以制备1,2,4-恶二唑环。