BENZIMIDAZOLE DERIVATIVES, COMPOSITIONS CONTAINING THEM, PREPARATION THEREOF AND USES THEREOFCompounds of formula (I) or pharmaceutically acceptable salts thereof: wherein R1, R2, R3, R4 and Z are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.A compound of foπnula I or a pharmaceutically acceptable salt thereof:whereinZ is selected from O= and S=;R1 is selected from CMoalkyl, C2-ι0alkenyl, C2-ι0alkynyl, R5R°N-C1-6alkyl, R5O-C].6 alkyl, R5C(=O)N(-R6)-C1-6alkyl, R5R6NS(=O)2-Cι-6alkyl, R5CS(=O)2N(-R6)-Cι-6alkyl, R5R°NC(=O)N(-R7)-Cι_6alkyl, R5R6NS(=O)2N(R7)-C,-6alkyl, C6-ι0aryl-Cι-6alkyl, C6-10aryl- C(=O)-C].6alkyl, C3-ιocycloalkyl-Cι-6alkyl, C4-8cycloalkenyl-C]-6alkyl, C3-6heterocyclyl-Cι- 6alkyl, C3-6heterocyclyl-C(=O)-C1-6alkyl, CMOhydrocarbylamino, R5R°N-, R5O-, R5C(=O)N(- R6)-, R5R6NS(=O)2-, R5CS(=O)2N(-R6)-, R5R°NC(=O)N(-R7)-, R5R6NS(=O)2N(R7)-, C6. loaryl, C6-ιoaryl-C(=O)-, C3-ιocycloalkyl, C -8cycloalkenyl, C3-6heterocyclyl and C3-6heterocyclyl-C(=O)-; wherein said Ci-ioalkyl, C2-ιoalkenyl, C2-ιoalkynyl, C6-ιoaryl-Cι-6alkyl, C6-ιoaryl-C(=O)-C1-6alkyl, C3.ιocycloalkyl-Cι.6alkyl, C -8cycloalkenyl-Cι-6alkyl, Cs-όheterocyclyl-Ci-ealkyl, C3-6heterocyclyl-C(=O)-Cι.6alkyl, Ci-iohydrocarbylamino, Cδ-ioaryl, C6-ιoaryl-C(=O)-, C3-ιocycloalkyl, C4.gcycloalkenyl, C3-6heterocyclyl or C3-6heterocyclyl-C(=O)- used in defining R1 is optionally substituted by one or more groups selected from halogen, cyano, nitro, methoxy, ethoxy, methyl, ethyl, hydroxy, and -NR5R6; R2 is selected from the group consisting of CMoalkyl, C2-ιoalkenyl, C2-ιoalkynyl, C3-10cycloalkyl, C3-ι0cycloalkyl-Cι-6alkyl, C4-8cycloalkenyl-Cι-6alkyl, C3-6heterocycloalkyl-Cι.. 6alkyl, C4-8cycloalkenyl, R5R°N-, C3-5heteroaryl, C6-ιoaryl and C3-6heterocycloalkyl, wherein said Cμioalkyl, C2-ιoalkenyl, C2-ιoalkynyl, C3-8cycloalkyl, C3-8cycloalkyl-Cι-6alkyl, C4-8cycloalkenyl-Cι-6alkyl, C3-6heterocycloalkyl-Cι-6alkyl, C4-8cycloalkenyl, C3-5heteroaryl, C6-ιoaryl or C3-6heterocycloalkyl used in defining R2 is optionally substituted by one or more groups selected from halogen, cyano, nitro, methoxy, ethoxy, methyl, ethyl, hydroxy, and - NR5R6; wherein R , R and R are independently selected from -H, Cι_6alkyl, C2-6alkenyl, C2-6alkynyl, and a divalent Cι-6group that together with another divalent R5, R6 or R7 forms a portion of a ring; andR3 is selected from R8, R8O-, and R'R'N-; each of R4, R8 and R9 is independently selected from -H, Ci-ioalkyl, C2-ιoalkenyl, C2-loalkynyl, C3-ιocycloalkyl, C3-ιocycloalkyl-Cι_6alkyl, C3-6heterocyclyl, C6-ιo ryl, C3-6heterocylcyl-Cι.6alkyl, C6-ιoaryl-Cι-6alkyl, and a divalent C1-6group that together with another divalent group selected from R4, R8 and R9 forms a portion of a ring, wherein said Ci-ioalkyl, C2-ιoalkenyl, C2-ιoalkynyl, C3_ιocycloalkyl, C3-ιocycloalkyl-Cι-6alkyl, C3_ όheterocyclyl, C6-ιoaryl, C3-6heterocylcyl-Cι_6alkyl, C6.ιoaryl-Cι-6alkyl, or divalent Cι-6group is optionally substituted by one or more groups selected from halogen, cyano, nitro, methoxy, ethoxy, methyl, ethyl, hydroxy and amino.
벤즈이미다졸 유도체, 그를 포함하는 조성물, 및 그의 제조방법 및 그의 용도하기 화학식 I의 화합물 또는 그의 제약상 허용가능한 염, 및 상기 화합물을 포함하는 제약 조성물이 제조된다. 이들은 치료, 특히 통증 치료에 유용하다. <화학식 I>  상기 화학식에서, R1, R2, R3, R4 및 Z는 본원에 정의된 바와 같다. 하기 화학식 I의 화합물 또는 그의 제약상 허용가능한 염. <화학식 I>  상기 화학식에서, Z는 O= 및 S=로부터 선택되고; R1은 C1-10알킬, C2-10알케닐, C2-10알키닐, R5R6N-C1-6알킬, R5O-C1-6알킬, R5C(=O)N(-R6)-C1-6알킬, R5R6NS(=O)2-C1-6알킬, R5CS(=O)2N(-R6)-C1-6알킬, R5R6NC(=O)N(-R7)-C1-6알킬, R5R6NS(=O)2N(R7)-C1-6알킬, C6-10아릴-C1-6알킬, C6-10아릴-C(=O)-C1-6알킬, C3-10시클로알킬-C1-6알킬, C4-8시클로알케닐-C1-6알킬, C3-6헤테로시클릴-C1-6알킬, C3-6헤테로시클릴-C(=O)-C1-6알킬, C1-10히드로카르빌아미노, R5R6N-, R5O-, R5C(=O)N(-R6)-, R5R6NS(=O)2-, R5CS(=O)2N(-R6)-, R5R6NC(=O)N(-R7)-, R5R6NS(=O)2N(R7)-, C6-10아릴, C6-10아릴-C(=O)-, C3-10시클로알킬, C4-8시클로알케닐, C3-6헤테로시클릴 및 C3-6헤테로시클릴-C(=O)-로부터 선택되며; 여기서 R1을 정의하는데 사용되는 상기 C1-10알킬, C2-10알케닐, C2-10알키닐, C6-10아릴-C1-6알킬, C6-10아릴-C(=O)-C1-6알킬, C3-10시클로알킬-C1-6알킬, C4-8시클로알케닐-C1-6알킬, C3-6헤테로시클릴-C1-6알킬, C3-6헤테로시클릴-C(=O)-C1-6알킬, C1-10히드로카르빌아미노, C6-10아릴, C6-10아릴-C(=O)-, C3-10시클로알킬, C4-8시클로알케닐, C3-6헤테로시클릴 또는 C3-6헤테로시클릴-C(=O)-는 할로겐, 시아노, 니트로, 메톡시, 에톡시, 메틸, 에틸, 히드록시 및 -NR5R6으로부터 선택되는 1개 이상의 기로 임의로 치환되고; R2는 C1-10알킬, C2-10알케닐, C2-10알키닐, C3-10시클로알킬, C3-10시클로알킬-C1-6알킬, C4-8시클로알케닐-C1-6알킬, C3-6헤테로시클로알킬-C1-6알킬, C4-8시클로알케닐, R5R6N-, C3-5헤테로아릴, C6-10아릴 및 C3-6헤테로시클로알킬로 구성된 군으로부터 선택되며; 여기서 R2를 정의하는데 사용되는 상기 C1-10알킬, C2-10알케닐, C2-10알키닐, C3-8시클로알킬, C3-8시클로알킬-C1-6알킬, C4-8시클로알케닐-C1-6알킬, C3-6헤테로시클로알킬-C1-6알킬, C4-8시클로알케닐, C3-5헤테로아릴, C6-10아릴 또는 C3-6헤테로시클로알킬은 할로겐, 시아노, 니트로, 메톡시, 에톡시, 메틸, 에틸, 히드록시, 및 -NR5R6으로부터 선택되는 1개 이상의 기로 임의로 치환되고; 여기서 R5, R6 및 R7은 독립적으로 -H, C1-6알킬, C2-6알케닐, C2-6알키닐, 및 또 다른 2가 R5, R6 또는 R7과 함께 고리의 일부분을 형성하는 2가 C1-6기로부터 선택되고; R3은 R8, R8O- 및 R8R9N-으로부터 선택되고; 각각의 R4, R8 및 R9는 독립적으로 -H, C1-10알킬, C2-10알케닐, C2-10알키닐, C3-10시클로알킬, C3-10시클로알킬-C1-6알킬, C3-6헤테로시클릴, C6-10아릴, C3-6헤테로시클릴-C1-6알킬, C6-10아릴-C1-6알킬, 및 R4, R8 및 R9로부터 선택되는 또 다른 2가 기와 함께 고리의 일부분을 형성하는 2가 C1-6기로부터 선택되며, 상기 C1-10알킬, C2-10알케닐, C2-10알키닐, C3-10시클로알킬, C3-10시클로알킬-C1-6알킬, C3-6헤테로시클릴, C6-10아릴, C3-6헤테로시클릴-C1-6알킬, C6-10아릴-C1-6알킬, 및 2가 C1-6기는 할로겐, 시아노, 니트로, 메톡시, 에톡시, 메틸, 에틸, 히드록시 및 아미노로부터 선택되는 1개 이상의 기로 임의로 치환된다.