NEW PYRIDINE DERIVATIVES AS LEPTIN RECEPTOR MODULATOR MIMETICSThe present invention relates to new compounds of formula (I), to pharmaceutical compositions comprising these compounds and to the use of these compounds as leptin receptor modulator mimetics in the preparation of medicaments against conditions associated with weight gain, type 2 diabetes and dyslipidemias.A compound of formula (I)or a pharmaceutically acceptable salt, solvate, hydrate, geometrical isomer, tautomer or optical isomer thereof, wherein:each R1 is independently selected from Ci_4-alkyl, Ci_4-alkoxy, halogen, cyano andCF3;R2 is Ci_6-alkyl (optionally substituted with one or more substituents selected from hydroxy, halogen and cyano) or -[C(R4A)(R4B)]m-R5;R3 is hydrogen, Ci_4-alkyl or fluoro-Ci_4-alkyl; R4A and R4B are each independently selected from hydrogen, halogen, hydroxy, C1-4- alkyl, fluoro-Ci_4-alkyl and hydroxy-Ci_4-alkyl;R5 is C3-8-cycloalkyl, Cβ-io-aryl, heterocyclyl or heteroaryl, each of which is optionally substituted with one or more substituents selected from hydroxy, halogen, cyano, nitro, CF3 and Ci_4-alkyl;m is 0, 1 or 2; and n is O, 1, 2, 3 or 4;with the proviso that the compound is not selected from: • pyridin-4-ylmethyl bis(2-chloroethyl)carbamate;• (2,6-dichloropyridin-4-yl)methyl dimethylcarbamate;• (2,6-dichloropyridin-4-ylmethyl propylcarbamate;• pyridin-4-ylmethyl methylcarbamate;• pyridin-4-ylmethyl isopropylcarbamate; • pyridin-4-ylmethyl [3 -(trifluoromethyl)phenyl] carbamate; - -• pyridin-4-ylmethyl (5-chloro-2-methoxyphenyl)carbamate;• pyridin-4-ylmethyl (2-methoxyphenyl)carbamate;• pyridin-4-ylmethyl (2,6-dimethylphenyl)carbamate;• pyridin-4-ylmethyl (2,4,6-trimethylphenyl)carbamate; • pyridin-4-ylmethyl (5-chloro-2,4-dimethoxyphenyl)carbamate;• pyridin-4-ylmethyl (2-methyl-5-nitrophenyl)carbamate;• pyridin-4-ylmethyl (3-ethylphenyl)carbamate;• pyridin-4-ylmethyl (2,4-dimethylphenyl)carbamate;• pyridin-4-ylmethyl (3,4,5-trimethoxyphenyl)carbamate; • pyridin-4-ylmethyl cyclohexyl(methyl)carbamate;• pyridin-4-ylmethyl pyridin-3-ylcarbamate;• pyridin-4-ylmethyl (4-methoxyphenyl)carbamate;• pyridin-4-ylmethyl (2,6-dichlorophenyl)carbamate;• pyridin-4-ylmethyl cyclohexylcarbamate; • pyridin-4-ylmethyl pyridin-4-ylcarbamate;• pyridin-4-ylmethyl (4-fluorophenyl)carbamate;• pyridin-4-ylmethyl [(2-chlorophenyl)methyl] carbamate;• pyridin-4-ylmethyl (3-nitrophenyl)carbamate;• pyridin-4-ylmethyl (3,5-dimethoxyphenyl)carbamate; • pyridin-4-ylmethyl (4-methylphenyl)carbamate;• pyridin-4-ylmethyl (3-chlorophenyl)carbamate;• pyridin-4-ylmethyl (4-chlorophenyl)carbamate;• (2,6-dichloropyridin-4-yl)methyl phenylcarbamate;• (2,6-dimethylpyridin-4-yl)methyl phenylcarbamate; • pyridin-4-ylmethyl phenylcarbamate; and• pyridin-4-ylmethyl (3,4-dimethoxyphenyl)carbamate.
렙틴 수용체 조절제 유사체로서의 신규한 피리딘 유도체본 발명은 하기 화학식 I의 신규한 화합물, 상기 화합물을 포함하는 약학적 조성물 및 체중 증가, 2형 당뇨병 및 이상지질혈증과 연관된 병태에 대한 약제의 제조에서 렙틴 수용체 조절제 유사체로서 상기 화합물의 용도에 관한 것이다: 화학식 I하기 화학식 I의 화합물 또는 이의 약학적으로 허용되는 염, 용매화물, 수화물, 기하 이성체, 호변 이성체 또는 광학 이성체:화학식 I상기 화학식에서, 각각의 R1은 독립적으로 C1-4-알킬, C1-4-알콕시, 할로겐, 시아노 및 CF3에서 선택되고;R2는 C1-6-알킬(히드록시, 할로겐 및 시아노에서 선택되는 1 이상의 치환기로 임의로 치환됨) 또는 -[C(R4A)(R4B)]m-R5이며;R3은 수소, C1-4-알킬 또는 플루오로-C1-4-알킬이고;R4A 및 R4B는 각각 독립적으로 수소, 할로겐, 히드록시, C1-4-알킬, 플루오로-C1-4-알킬 및 히드록시-C1-4-알킬에서 선택되고;R5는 C3-8-시클로알킬, C6-10-아릴, 헤테로시클릴 또는 헤테로아릴이고, 이들 각각은 히드록시, 할로겐, 시아노, 니트로, CF3 및 C1-4-알킬에서 선택되는 1 이상의 치환기로 임의로 치환되며;m은 0, 1 또는 2이고;n은 0, 1, 2, 3 또는 4이며;단, 화합물은 하기에서 선택되지 않는다:· 피리딘-4-일메틸 비스(2-클로로에틸)카르바메이트;· (2,6-디클로로피리딘-4-일)메틸 디메틸카르바메이트;· (2,6-디클로로피리딘-4-일메틸 프로필카르바메이트;· 피리딘-4-일메틸 메틸카르바메이트;· 피리딘-4-일메틸 이소프로필카르바메이트;· 피리딘-4-일메틸 [3-(트리플루오로메틸)페닐]카르바메이트;· 피리딘-4-일메틸 (5-클로로-2-메톡시페닐)카르바메이트;· 피리딘-4-일메틸 (2-메톡시페닐)카르바메이트;· 피리딘-4-일메틸 (2,6-디메틸페닐)카르바메이트;· 피리딘-4-일메틸 (2,4,6-트리메틸페닐)카르바메이트;· 피리딘-4-일메틸 (5-클로로-2,4-디메톡시페닐)카르바메이트;· 피리딘-4-일메틸 (2-메틸-5-니트로페닐)카르바메이트;· 피리딘-4-일메틸 (3-에틸페닐)카르바메이트;· 피리딘-4-일메틸 (2,4-디메틸페닐)카르바메이트;· 피리딘-4-일메틸 (3,4,5-트리메톡시페닐)카르바메이트;· 피리딘-4-일메틸 시클로헥실(메틸)카르바메이트;· 피리딘-4-일메틸 피리딘-3-일카르바메이트;· 피리딘-4-일메틸 (4-메톡시페닐)카르바메이트;· 피리딘-4-일메틸 (2,6-디클로로페닐)카르바메이트;· 피리딘-4-일메틸 시클로헥실카르바메이트;· 피리딘-4-일메틸 피리딘-4-일카르바메이트;· 피리딘-4-일메틸 (4-플루오로페닐)카르바메이트;· 피리딘-4-일메틸 [(2-클로로페닐)메틸]카르바메이트;· 피리딘-4-일메틸 (3-니트로페닐)카르바메이트;· 피리딘-4-일메틸 (3,5-디메톡시페닐)카르바메이트;· 피리딘-4-일메틸 (4-메틸페닐)카르바메이트;· 피리딘-4-일메틸 (3-클로로페닐)카르바메이트;· 피리딘-4-일메틸 (4-클로로페닐)카르바메이트;· (2,6-디클로로피리딘-4-일)메틸 페닐카르바메이트;· (2,6-디메틸피리딘-4-일)메틸 페닐카르바메이트;· 피리딘-4-일메틸 페닐카르바메이트; 및· 피리딘-4-일메틸 (3,4-디메톡시페닐)카르바메이트.