Arylhydrazides containing a 2-pyridone moiety as selective antibacterial agentsThe present invention belongs to the field of antibacterial agents, more specifically to antibacterials for treating Acinetobacter baumannii infections. The invention provides arylhydrazides containing a 2-pyridone moiety, according to formula (I), which show selective antibacterial activity against A. baumannii. The invention also relates to their use as medicaments and specifically as antibacterials for the treatment of A. baumannii infections, as well as to a process for their preparation and to pharmaceutical compositions containing them.A kind of compound of formulas of 1.- (I)：Or its pharmaceutically acceptable salt or its solvate,WhereinA is selected from A1、A2、A3And A4Group；A1ForA2ForA3ForA4ForR1And R2Independently selected from hydrogen, C1-4Alkyl, halo C1-4Alkyl, hydroxyl C1-4Alkyl and C1-4Alkoxy C1-4Alkyl；R3、R4、R5、R6And R7Independently selected from hydrogen ,-OH, halogen, C1-6Alkyl, C3-6Cycloalkyl ,-NR12R13、-N(R12)COR13、- N(R12)SO2R13, halo C1-6Alkyl, hydroxyl C1-6Alkyl, C1-4Alkoxyl, C1-4Alkoxy C1-6Alkyl ,-COOR12、-CN、- CONR12R13、-SO2-C1-4Alkyl ,-SO2-O-C1-4Alkyl and-SO2-NR12R13；R8Selected from C1-6Alkyl, C2-6Thiazolinyl, C2-6Alkynyl, halo C1-6Alkyl, hydroxyl C1-4Alkyl, C1-4Alkoxyl, C1-4Alkoxyl C1-4Alkyl, C3-6Cycloalkyl C1-4Alkyl, PhC1-4Alkyl and-C1-4Alkyl-CONR12R13；R9、R10And R11Independently selected from hydrogen, C1-6Alkyl, C3-6Cycloalkyl C0-4Alkyl ,-NR12R13、-N(R12)COR13、-N(R12) SO2R13, halo C1-6Alkyl, hydroxyl C1-6Alkyl, C1-4Alkoxyl, C1-4Alkoxy C1-6Alkyl ,-COOR12、-CN、- CONR12R13、-SO2-C1-4Alkyl ,-SO2-O-C1-4Alkyl and-SO2-NR12R13；AndEach R12And R13Independently selected from hydrogen and C1-4Alkyl；Condition is to exclude following product：1- methyl -6- oxo -1,6- dihydro-pyrido -2- carboxylic acid N '-phenyl hydrazide,1- benzyl -2- oxo -1,2- dihydro-pyrido -3- carboxylic acid N '-(2- (trifluoromethyl) phenyl)-hydrazides,1- benzyl -4,6- dimethyl -2- oxo -1,2- dihydro-pyrido -3- carboxylic acid N '-phenyl-hydrazides,1- methyl -2- oxo -1,2- dihydro-pyrido -4- carboxylic acid N '-(2,4,6- trichloro-benzene base)-hydrazides,1- ((3- aminomethyl phenyls) methyl) -2- oxo -1,2- dihydro-pyrido -3- carboxylic acid N '-(3- (trifluoromethyl) phenyl)-acyl Hydrazine and1- ((2- chlorophenyls) methyl) -6- oxo -1,6- dihydro-pyrido -3- carboxylic acid N '-phenyl-N '-methyl-hydrazEde.
선택적 항균제로서의 2-피리돈 모이어티를 함유하는 아릴하이드라자이드본 발명은 항균제의 분야, 더욱 구체적으로는 아시네토박터 바우마니이(Acinetobacter baumannii) 감염을 치료하기 위한 항균제에 속한다. 본 발명은, 에이. 바우마니이에 대해서 선택적 항균 활성을 나타내는, 하기 화학식 (I)에 따른 2-피리돈 모이어티를 함유하는 아릴하이드라자이드를 제공한다. 본 발명은 또한 약제로서의, 그리고 구체적으로는 에이. 바우마니이 감염의 치료를 위한 항균제로서의 그의 용도뿐만 아니라, 이의 제조방법과, 이를 함유하는 약제학적 조성물에 관한 것이다.하기 화학식 (I)의 화합물, 또는 이의 약제학적으로 허용 가능한 염 또는 용매화물:[이미지]식 중,A는 A1, A2, A3 및 A4로부터 선택된 라디칼이고;A1은 [이미지]이며;A2는 [이미지]이고;A3은 [이미지]이며;A4는 [이미지]이고;R1 및 R2는 독립적으로 수소, C1-4알킬, 할로C1-4알킬, 하이드록시C1-4알킬 및 C1-4알콕시C1-4알킬로부터 선택되며;R3, R4, R5, R6 및 R7은 독립적으로 수소, -OH, 할로겐, C1-6알킬, C3-6사이클로알킬, -NR12R13, -N(R12)COR13, -N(R12)SO2R13, 할로C1-6알킬, 하이드록시C1-6알킬, C1-4알콕시, C1-4알콕시C1-6알킬, -COOR12, -CN, -CONR12R13,-SO2-C1-4알킬, -SO2-O-C1-4알킬 및 -SO2-NR12R13으로부터 선택되며;R8은 C1-6알킬, C2-6알켄일, C2-6알킨일, 할로C1-6알킬, 하이드록시C1-4알킬, C1-4알콕시, C1-4알콕시C1-4알킬, C3-6사이클로알킬C1-4알킬, PhC1-4알킬 및 -C1-4알킬- CONR12R13으로부터 선택되며;R9, R10 및 R11은 독립적으로 수소, C1-6알킬, C3-6사이클로알킬C0-4알킬, -NR12R13, -N(R12)COR13, -N(R12)SO2R13, 할로C1-6알킬, 하이드록시C1-6알킬, C1-4알콕시, C1-4알콕시C1-6알킬, -COOR12, -CN, -CONR12R13,-SO2-C1-4알킬, -SO2-O-C1-4알킬 및 -SO2-NR12R13으로부터 선택되며; 그리고각각의 R12 및 R13은 독립적으로 수소 및 C1-4알킬로부터 선택되되;단, 이하의 생성물은 배제된다:1-메틸-6-옥소-1,6-다이하이드로-피리딘-2-카복실산 N'-페닐하이드라자이드,1-벤질-2-옥소-1,2-다이하이드로-피리딘-3-카복실산 N'-(2-(트라이플루오로메틸)페닐)-하이드라자이드,1-벤질-4,6-다이메틸-2-옥소-1,2-다이하이드로-피리딘-3-카복실산 N'-페닐-하이드라자이드,1-메틸-2-옥소-1,2-다이하이드로-피리딘-4-카복실산 N'-(2,4,6-트라이클로로페닐)-하이드라자이드,1-((3-메틸페닐)메틸)-2-옥소-1,2-다이하이드로-피리딘-3-카복실산 N'-(3-(트라이플루오로메틸)페닐)-하이드라자이드 및1-((2-클로로페닐)메틸)-6-옥소-1,6-다이하이드로-피리딘-3-카복실산 N'-페닐-N'-메틸-하이드라자이드.