NEW COMPOUNDS VThe 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, optical isomer or JV-oxide thereof, wherein:A is a pyridine ring;Y is O, N(R3) or CH2; W is O, N(R4) or CH2;each R1 is independently selected from Ci_4-alkyl, Ci_4-alkoxy, halogen, cyano and CF3; each R2 is independently selected from hydroxy and Ci_4-alkyl;R3 is hydrogen or Ci_4-alkyl;R4 is selected from hydrogen, Ci_6-alkyl, Ci_6-acyl, phenyl and benzyl, wherein phenyl and benzyl are optionally substituted with one or more substituents selected from halogen, cyano, CF3, C^-alkyl, Ci_6-alkoxy, phenyl and phenoxy;a and b are each independently 0, 1 or 2; c is 1 or 2; and d is 0, 1 or 2;provided that the compound is not selected from the group consisting of:• N-(4-pyridinylmethyl)-4-morpho linecarboxamide;• 4-(3 -methylphenyl)-N-(2-pyridinylmethyl)- 1 -piperazinecarboxamide;• 4-(4-fluorophenyl)-N-(3 -pyridinylmethyl)- 1 -piperazinecarboxamide; • N-(2-pyridinylmethyl)-4-morpho linecarboxamide; - -• 4-(2-methylphenyl)-N-(3 -pyridinylmethyl)- 1 -piperazinecarboxamide;• 4-(5 -chloro-2-methylphenyl)-N-(3 -pyridinylmethyl)- 1 -piperazinecarboxamide;• N-(3 -pyridinylmethyl)-4-morpho linecarboxamide;• (2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-N,2,5-trimethyl-N-(2-pyridinyl- 5 methyl)- 1 -piperazinecarboxamide;• (2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[(3-methyl-2- pyridinyl)methyl] - 1 -piperazinecarboxamide;• (2-pyridinyl)methyl 4-methylpiperazine-l-carboxylate;• (2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-(3-pyridinyl- i o methyl)- 1 -piperazinecarboxamide;• 2-(2-pyridinyl)ethyl 4-methylpiperazine-l-carboxylate;• 4-phenyl-N-[2-(2-pyridinyl)ethyl]- 1 -piperazinecarboxamide;• 4-(2,3-dimethylphenyl)-N-(3-pyridinylmethyl)- 1 -piperazinecarboxamide;• (2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[2-(4-pyridinyl)- 15 ethyl] - 1 -piperazinecarboxamide;• 4-(4-chlorophenyl)-N-(3 -pyridinylmethyl)- 1 -piperidinecarboxamide;• N- [2-(4-pyridinyl)ethyl]-4-morpho linecarboxamide;• 4-phenyl-N-(3 -pyridinylmethyl)- 1 -piperazinecarboxamide;• (2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-N,2,5-trimethyl-N-(3-pyridinyl- 20 methyl)- 1 -piperazinecarboxamide;• 4-phenyl-N-(2 -pyridinylmethyl)- 1 -piperazinecarboxamide;• N-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl]-4-morpholinecarboxamide;• (2R,5S)-N-[(6-chloro-2-pyridinyl)methyl]-4-[4-cyano-3-(trifluoromethyl)phenyl]- 2,5-dimethyl- 1 -piperazinecarboxamide;25 • (2R,5S)-N-[(6-chloro-3-pyridinyl)methyl]-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl- 1 -piperazinecarboxamide;• 1 -[3-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]- 1 -oxopropyl]-4-phenyl- piperazine;• 1 -[3-(2-pyridyl)propionyl]-piperidine;30 • l-methyl-4-[l-oxo-3-(3-pyridinyl)propyl]-piperazine;• 1 -[3-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]- 1 -oxopropyl]-4-methyl- piperazine;• 4-[3-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]- 1 -oxopropyl]-morpholine; - -• (6-methylpyridin-2-yl)methyl 4-(2,4,6-trimethoxybenzyl)-piperazine- 1 - carboxylate;• 4-(5-fluoro-2-methoxybenzyl)-N-[2-(pyridin-2-yl)ethyl]- 1 - piperazinecarboxamide; • N- [(6-methoxy-3 -pyridinyl)methyl] -4-phenyl- 1 -piperazinecarboxamide;• 4-(4-fluorophenyl)-N- [(6-methoxy-3 -pyridinyl)methyl] - 1 -piperazinecarboxamide;• 4-(2-fluorophenyl)-N- [(6-methoxy-3 -pyridinyl)methyl] - 1 -piperazinecarboxamide;• (2R,5 S)-4- [4-cyano-3 -(trifluoromethyl)phenyl] -N- [(6-methoxy-3 -pyridinyl)- methyl]-2,5-dimethyl- 1 -piperazinecarboxamide; • l-[l-oxo-3-(3-pyridinyl)propyl]-piperazine;• 4-[ 1 -oxo-3-(2-pyridinyl)propyl]-morpholine;• 4-(3 -chlorophenyl)-N- [(6-methoxy-3 -pyridinyl)methyl] - 1 -piperazinecarboxamide;• 4-(4-methoxyphenyl)-N-(3 -pyridinylmethyl)- 1 -piperazinecarboxamide; and• N- [(I -oxidopyridin-3-yl)methyl]piperidine- 1 -carboxamide.
신규한 화합물 Ｖ본 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, 광학 이성체 또는 N-옥시드:화학식 I상기 화학식에서,A는 피리딘 고리이고;Y는 O, N(R3) 또는 CH2이며;W는 O, N(R4) 또는 CH2이며;각각의 R1은 독립적으로 C1-4-알킬, C1-4-알콕시, 할로겐, 시아노 및 CF3에서 선택되고;각각의 R2는 독립적으로 히드록시 및 C1-4-알킬에서 선택되며;R3은 수소 또는 C1-4-알킬이고;R4는 수소, C1-6-알킬, C1-6-아실, 페닐 및 벤질에서 선택되고, 여기서 페닐 및 벤질은 할로겐, 시아노, CF3, C1-6-알킬, C1-6-알콕시, 페닐 및 페녹시에서 선택되는 1 이상의 치환기로 임의로 치환되고;a 및 b는 독립적으로 0, 1 또는 2이고;c는 1 또는 2이고;d는 0, 1 또는 2이고;단, 상기 화합물은 하기로 구성된 군에서 선택되지 않는다:· N-(4-피리디닐메틸)-4-모르폴린카르복스아미드;· 4-(3-메틸페닐)-N-(2-피리디닐메틸)-1-피페라진카르복스아미드;· 4-(4-플루오로페닐)-N-(3-피리디닐메틸)-1-피페라진카르복스아미드;· N-(2-피리디닐메틸)-4-모르폴린카르복스아미드;· 4-(2-메틸페닐)-N-(3-피리디닐메틸)-1-피페라진카르복스아미드;· 4-(5-클로로-2-메틸페닐)-N-(3-피리디닐메틸)-1-피페라진카르복스아미드;· N-(3-피리디닐메틸)-4-모르폴린카르복스아미드;· (2R,5S)-4-[4-시아노-3-(트리플루오로메틸)페닐]-N,2,5-트리메틸-N-(2-피리디닐메틸)-1-피페라진카르복스아미드;· (2R,5S)-4-[4-시아노-3-(트리플루오로메틸)페닐]-2,5-디메틸-N-[(3-메틸-2-피리디닐)메틸]-1-피페라진카르복스아미드;· (2-피리디닐)메틸 4-메틸피페라진-1-카르복실레이트;· (2R,5S)-4-[4-시아노-3-(트리플루오로메틸)페닐]-2,5-디메틸-N-(3-피리디닐메틸)-1-피페라진카르복스아미드;· 2-(2-피리디닐)에틸 4-메틸피페라진-1-카르복실레이트;· 4-페닐-N-[2-(2-피리디닐)에틸]-1-피페라진카르복스아미드;· 4-(2,3-디메틸페닐)-N-(3-피리디닐메틸)-1-피페라진카르복스아미드;· (2R,5S)-4-[4-시아노-3-(트리플루오로메틸)페닐]-2,5-디메틸-N-[2-(4-피리디닐)에틸]-1-피페라진카르복스아미드;· 4-(4-클로로페닐)-N-(3-피리디닐메틸)-1-피페리딘카르복스아미드;· N-[2-(4-피리디닐)에틸]-4-모르폴린카르복스아미드;· 4-페닐-N-(3-피리디닐메틸)-1-피페라진카르복스아미드;· (2R,5S)-4-[4-시아노-3-(트리플루오로메틸)페닐]-N,2,5-트리메틸-N-(3-피리디닐메틸)-1-피페라진카르복스아미드;· 4-페닐-N-(2-피리디닐메틸)-1-피페라진카르복스아미드;· N-[[3-클로로-5-(트리플루오로메틸)-2-피리디닐]메틸]-4-모르폴린카르복스아미드;· (2R,5S)-N-[(6-클로로-2-피리디닐)메틸]-4-[4-시아노-3-(트리플루오로메틸)페닐]-2,5-디메틸-1-피페라진카르복스아미드;· (2R,5S)-N-[(6-클로로-3-피리디닐)메틸]-4-[4-시아노-3-(트리플루오로메틸)페닐]-2,5-디메틸-1-피페라진카르복스아미드;· 1-[3-[3-클로로-5-(트리플루오로메틸)-2-피리디닐]-1-옥소프로필]-4-페닐-피페라진;· 1-[3-(2-피리딜)프로피오닐]-피페리딘;· 1-메틸-4-[1-옥소-3-(3-피리디닐)프로필]-피페라진;· 1-[3-[3-클로로-5-(트리플루오로메틸)-2-피리디닐]-1-옥소프로필]-4-메틸-피페라진;· 4-[3-[3-클로로-5-(트리플루오로메틸)-2-피리디닐]-1-옥소프로필]-모르폴린;· (6-메틸피리딘-2-일)메틸 4-(2,4,6-트리메톡시벤질)-피페라진-1-카르복실레이트;· 4-(5-플루오로-2-메톡시벤질)-N-[2-(피리딘-2-일)에틸]-1-피페라진카르복스아미드;· N-[(6-메톡시-3-피리디닐)메틸]-4-페닐-1-피페라진카르복스아미드;· 4-(4-플루오로페닐)-N-[(6-메톡시-3-피리디닐)메틸]-1-피페라진카르복스아미드;· 4-(2-플루오로페닐)-N-[(6-메톡시-3-피리디닐)메틸]-1-피페라진카르복스아미드;· (2R,5S)-4-[4-시아노-3-(트리플루오로메틸)페닐]-N-[(6-메톡시-3-피리디닐)메틸]-2,5-디메틸-1-피페라진카르복스아미드;· 1-[1-옥소-3-(3-피리디닐)프로필]-피페라진;· 4-[1-옥소-3-(2-피리디닐)프로필]-모르폴린;· 4-(3-클로로페닐)-N-[(6-메톡시-3-피리디닐)메틸]-1-피페라진카르복스아미드;· 4-(4-메톡시페닐)-N-(3-피리디닐메틸)-1-피페라진카르복스아미드; 및· N-[(1-옥시도피리딘-3-일)메틸]피페리딘-1-카르복스아미드.