6-acetamido-3-hydroxy-7-methyl-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole-5,8-dione 3-methoxyacetate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-acetamido-3-hydroxy-7-methyl-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole-5,8-dione 3-methoxyacetate
• 英文别名: (6-acetamido-7-methyl-5,8-dioxo-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-3-yl) 2-methoxyacetate；NSC651084；1H-Pyrrolo[1,2-a]benzimidazole-5,8-dione, 6-(acetylamino)-2,3-dihydro-3-[methoxy(acetyloxy)]-7-methyl-
• 化学式: C₁₆H₁₇N₃O₆
• 分子量: 347.327
• InChiKey: IEGPEJKOKNPIHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  甲氧基乙酰氯 、 6-acetamido-3-hydroxy-7-methyl-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole-5,8-dione 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以73%的产率得到6-acetamido-3-hydroxy-7-methyl-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole-5,8-dione 3-methoxyacetate
  参考文献：
  名称：

  Pyrrolo[1,2-a]benzimidazole-Based Quinones and Iminoquinones. The Role of the 3-Substituent on Cytotoxicity

  摘要：

  The influence of the 3-substituent on the cytotoxicity of the 6-aziridinylpyrrolo[1,2-a]benzimidazole quinones (PBIs), the 6-acetamidopyrrolo[1,2-a]benzimidazole quinones (APBIs), and the 6-acetamidopyrrolo[1,2-a]benzimidazole iminoquinones (imino-APBIs) was investigated by comparing LC(50) mean graphs consisting of 60 cancer lines. Increasing lipophilicity of the 3-substituent of PBIs and APBIs increased the cytotoxicity specifically in melanoma cell lines. The 3-substituent does not influence DNA cleavage by reduced PBIs, except for the S-carbamate derivative which shows enhanced cleavage. This property of the 3-carbamate is rationalized in terms of the PBI major groove binding model. The imino-APBIs show enhanced cytotoxicity in melanoma and renal cancer cell lines; the correlation coefficient for log LC(50) VS log lipophilicity is 0.8 to 0.9. COMPARE correlations revealed that the PBIs are activated by DT-diaphorase but that the APBIs and imino-APBIs are inactivated by this enzyme. Thus the latter two agents are cytotoxic only as quinones. It was noted that APBIs possess a similar cytotoxic profile to three anthracycline analogues. This observation suggests mechanistic similarities between both types of cytotoxic agents. Major conclusions of this study pertain to the design of agents displaying cytotoxicity specifically against melanoma and renal cancers and to the use of 60-cell line mean graphs and COMPARE in cancer drug QSAR.

  DOI：

  10.1021/jm00001a016

文献信息

• Bone morphogenetic protein pathway activation, compositions for ossification, and methods related thereto
  申请人：EMORY UNIVERSITY

  公开号：US10434220B2

  公开（公告）日：2019-10-08

  The disclosure relates to compounds and compositions for bone formation, fracture treatment, bone grafting, bone fusion, cartilage maintenance and repair, and methods related thereto. In certain embodiments, the disclosure relates to compositions comprising one or more compound(s) disclosed herein derivatives, or salt thereof, for use in bone growth processes. In a typical embodiment, a bone graft composition is implanted in a subject at a site of desired bone growth or enhancement. In certain embodiments, compounds disclosed herein are useful for managing obesity and diabetes or other metabolic syndromes by modulation of brown fat.

  本公开涉及用于骨形成、骨折治疗、骨移植、骨融合、软骨维护和修复的化合物和组合物，以及与之相关的方法。在某些实施方案中，本公开涉及包含一种或多种本文公开的化合物衍生物或其盐的组合物，用于骨生长过程。在一个典型的实施方案中，骨移植组合物被植入受试者所需骨生长或增强的部位。在某些实施方案中，本文公开的化合物可通过调节棕色脂肪来控制肥胖和糖尿病或其他代谢综合征。
• BONE MORPHOGENETIC PROTEIN PATHWAY ACTIVATION, COMPOSITIONS FOR OSSIFICATION, AND METHODS RELATED THERETO
  申请人：EMORY UNIVERSITY

  公开号：US20150148292A1

  公开（公告）日：2015-05-28

  The disclosure relates to compounds and compositions for bone formation, fracture treatment, bone grafting, bone fusion, cartilage maintenance and repair, and methods related thereto. In certain embodiments, the disclosure relates to compositions comprising one or more compound(s) disclosed herein, such as 2-(2-Methoxybenzylidene)-1-indan-one; N-(4-arsonophenyl)glycine; 1,2-Benzenedicarboxylic acid, 1-(1-methylheptyl)ester; (4′-hydroxybiphenyl-4-yl) (phenyl)methanone; 2,2-dimethylchroman-6-carboxylic acid, (4,7-dihydroxy-8-methyl-2-oxo-2H-chromen-3-yl)amide; Ethyl 2-((4-chlorophenyl)thio)-1,3-benzothiazol-6-yl carbamate; Ethyl (2-(azepan-1-yl)benzo[d]thiazol-6-yl) carbamate; Porfiromycin; 1,3-benzodioxol-5-yl-[4-(3,4,5-trimethoxybenzoyl)-3-furyl]methanone; Tricinolone acetophenonide; 2,4-bis(3,4-dimethoxyphenyl)-4H-pyrano[3,2-c]chromen-5-one; Methyl 5-fluoro-4-methoxy-2,6-dioxohexahydro-5-pyrimidine carboxylate; 5-(naphthalen-1-yl)-1-phenyl-1h-tetrazole; 5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazol-2-ol; N-[2,4,5-trimethyl-4-(trichloromethyl)cyclohexa-2,5-dien-1-ylidene]hydroxylamine; 4-benzoyl-3,4-dihydro-Benzo[f]quinoline-3-carbonitrile; 2-nitro-3-phenylspiro[cyclopropane-1,9′-fluorene]; 3-[4-(furan-2-ylmethyl)-5-sulfanylidene-1,2,4-dithiazolidin-3-ylidene]-1,1-dimethyl-thiourea; (6-acetamido-7-methyl-5,8-dioxo-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-3-yl)2-methoxyacetate; 5-Iodo-1H-indole-2,3-dione; 4,5-dihydro-1,2,9,10-tetramethoxy dibenzo[de,g]quinoline-6-carboxylic acid, ethyl ester; [2,6-bis(2,4-dimethylphenyl)-4-(2-methoxyacetyl)oxy-phenyl]2-methoxyacetate; 5,11-dimethyl-2-(2-piperidin-1-ylethyl)-6H-pyrido[4,3-b]carbazol-2-ium-9-ol; 2-[3-[[4-[(3-nitroacridin-9-yl)amino]phenyl]sulfamoyl]propyl]guanidine; 1-[[2-(dimethylamino)ethyl]amino]-7-hydroxy-4-methyl-9H-thioxanthen-9-one; 5-amino-1H-1,2,4-triazole-3-carboxylic acid, methyl ester; methyl N-cyano-N′-prop-2-en-1-ylcarbamimidothioate; 5,7-dinitro-8-quinolinol; 5-nitrosoquinolin-8-ol; Cantharidin; 1,7-Diaminoacridine; 3-Methyl-3-(1-naphthyl)-2-benzofuran-1(3H)-one; Dichlorolapachol; Lycobetaine; 6-(1-aziridinyl)-2,3-dihydro-3-(propionyl)-7-methyl-1H-Pyrrolo[1,8]-dione; 4-Nitroestrone 3-methyl ether; 5,11-dimethyl-6H-pyrido[4,3-b]carbazole-1-carboxamide hydrochloride; 5-Methoxysterigmatocysin; (6-acetamido-7-methyl-5,8-dioxo-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-3-yl)2-methoxyacetate; Horminon; 7′,8′-dimethyl-2′-oxo-4′,4a′,6a′,7′-tetrahydro-2′H-spiro[oxirane-2,1′-pentaleno[1,6a-c]pyran]-5′-carboxylate; Nybomycin acetate; 5H-[1,6]indeno[1,2-c]isoquinoline-5,12-dione; 2,3-dimethoxy-6-methyl-Nitidine; Iproplatin; 3-[(deoxyhexosyl)oxy]-2-(3,4-di-hydroxyphenyl)-6,8-dihdroxy-4H-1-Benzopyran-4-one; 2-O-benzyl 8-O-methyl 3-(4-methylphenyl)sulfonyl-4,5-dioxo-6H-pyrrolo[3,2-e]indole-2,8-dicarboxylate; 6-bromo-5,8-dihydroxy-7-[4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]naphthalene-1,4-dione; 5-methylbenzo[c]phenanthridin-5-ium-2,3,8,9-tetrol; (6-acetyl-4-oxo-1,3-diphenyl-2-sulfanylidenethieno[2,3-d]pyrimidin-5-yl)-2,4-dichlorobenzoate; N—[C-[4-[bis(2-cyanoethyl)amino]-2-methylphenyl]-N-(4-methylanilino)carbonimidoyl]imino-4-methylbenzamide; Gelcohol; Curcumin; Tirandamycin; Noscapine; Aristolochic acid; Himbacine; Fumagillin; Fumitremorgin C; Physalin B; derivatives, or salt thereof, for use in bone growth processes. In a typical embodiment, a bone graft composition is implanted in a subject at a site of desired bone growth or enhancement. In certain embodiments, compounds disclosed herein are useful for managing obesity and diabetes or other metabolic syndromes by modulation of brown fat.
• [EN] BONE MORPHOGENETIC PROTEIN PATHWAY ACTIVATION, COMPOSITIONS FOR OSSIFICATION, AND METHODS RELATED THERETO<br/>[FR] ACTIVATION DE LA VOIE DES PROTÉINES MORPHOGÉNÉTIQUES OSSEUSES, COMPOSITIONS POUR UNE OSSIFICATION ET PROCÉDÉS ASSOCIÉS
  申请人：UNIV EMORY

  公开号：WO2014011540A1

  公开（公告）日：2014-01-16

  The disclosure relates to compounds and compositions for bone formation, fracture treatment, bone grafting, bone fusion, cartilage maintenance and repair, and methods related thereto. In certain embodiments, the disclosure relates to compositions comprising one or more compound(s) disclosed herein, such as 2-(2-Methoxybenzylidene)-1-indanone; N-(4-arsonophenyl)glycine; 1,2-Benzenedicarboxylic acid, 1-(1-methylheptyl) ester; (4'-hydroxybiphenyl-4-yl)(phenyl)methanone; 2,2-dimethylchroman-6-carboxylic acid, (4,7-dihydroxy-8-methyl-2-oxo-2H-chromen-3-yl)amide; Ethyl 2-((4-chlorophenyl)thio)-1,3-benzothiazol-6-yl carbamate; Ethyl (2-(azepan-1-yl)benzo[d]thiazol-6-yl) carbamate; Porfiromycin;1,3-benzodioxol-5-yl-[4-(3,4,5-trimethoxybenzoyl)-3-furyl]methanone; Tricinolone acetophenonide; 2,4-bis(3,4-dimethoxyphenyl)-4H-pyrano[3,2-c]chromen-5-one; Methyl 5-fluoro-4-methoxy-2,6-dioxohexahydro-5-pyrimidine carboxylate; 5-(naphthalen-1-yl)-1-phenyl-1h-tetrazole; 5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazol-2-ol; N-[2,4,5-trimethyl-4-(trichloromethyl)cyclohexa-2,5-dien-1-ylidene]hydroxylamine; 4-benzoyl-3,4-dihydro-Benzo[f]quinoline-3-carbonitrile; 2-nitro-3-phenylspiro[cyclopropane-1,9'-fluorene]; 3-[4-(furan-2-ylmethyl)-5-sulfanylidene-1,2,4-dithiazolidin-3-ylidene]-1,1-dimethylthiourea; (6-acetamido-7-methyl-5,8-dioxo-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-3-yl) 2-methoxyacetate; 5-Iodo-1H-indole-2,3-dione; 4,5-dihydro-1,2,9,10-tetramethoxy dibenzo[de,g]quinoline-6-carboxylic acid, ethyl ester; [2,6-bis(2,4-dimethylphenyl)-4-(2-methoxyacetyl)oxy-phenyl] 2-methoxyacetate; 5,11-dimethyl-2-(2-piperidin-1-ylethyl)-6H-pyrido[4,3-b]carbazol-2-ium-9-ol; 2-[3-[[4-[(3-nitroacridin-9-yl)amino]phenyl]sulfamoyl] propyl]guanidine; 1-[[2-(dimethylamino)ethyl]amino]-7-hydroxy-4-methyl-9H-thioxanthen-9-one; 5-amino-1H-1,2,4-triazole-3-carboxylic acid, methyl ester; methyl N-cyano-N'-prop-2-en-1-ylcarbamimidothioate; 5,7-dinitro-8-quinolinol; 5-nitrosoquinolin-8-ol; Cantharidin; 1,7-Diaminoacridine; 3-Methyl-3-(1-naphthyl)-2-benzofuran-1(3H)-one; Dichlorolapachol; Lycobetaine; 6-(1-aziridinyl)- 2,3-dihydro-3-(propionyl)-7-methyl-1H-Pyrrolo [1,8]-dione; 4-Nitroestrone 3-methyl ether; 5,11-dimethyl-6H-pyrido[4,3-b] carbazole-1-carboxamide hydrochloride; 5-Methoxysterigmatocysin; (6-acetamido-7-methyl-5,8-dioxo-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-3-yl) 2-methoxyacetate; Horminon; 7',8'-dimethyl-2'-oxo-4',4a',6a',7'- tetrahydro-2'H-spiro[oxirane-2,1'-pentaleno[1,6a-c]pyran]-5'-carboxylate; Nybomycin acetate; 5H-[1,6]indeno[1,2-c]isoquinoline-5,12-dione; 2,3-dimethoxy-6-methyl-Nitidine; Iproplatin; 3-[(deoxyhexosyl)oxy]-2-(3,4-dihydroxyphenyl)-6,8-dihdroxy-4H-1-Benzopyran-4-one; 2-O-benzyl 8-O-methyl 3-(4-methylphenyl)sulfonyl-4,5-dioxo-6H- pyrrolo[3,2-e]indole-2,8- dicarboxylate;6-bromo-5,8-dihydroxy-7-[4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl] naphthalene -1,4-dione; 5-methylbenzo[c]phenanthridin-5-ium-2,3,8,9-tetrol; (6-acetyl-4-oxo-1,3-diphenyl-2-sulfanylidenethieno[2,3-d]pyrimidin-5-yl)-2,4-dichlorobenzoate; N-[C-[4-[bis(2-cyanoethyl)amino]-2-methylphenyl]-N-(4-methylanilino)carbonimidoyl]imino-4-methylbenzamide; Gelcohol; Curcumin; Tirandamycin; Noscapine; Aristolochic acid; Himbacine; Fumagillin; Fumitremorgin C; Physalin B; derivatives, or salt thereof, for use in bone growth processes. In a typical embodiment, a bone graft composition is implanted in a subject at a site of desired bone growth or enhancement. In certain embodiments, compounds disclosed herein are useful for managing obesity and diabetes or other metabolic syndromes by modulation of brown fat.
• Pyrrolo[1,2-a]benzimidazole-Based Quinones and Iminoquinones. The Role of the 3-Substituent on Cytotoxicity
  作者：William G. Schulz、Imadul Islam、Edward B. Skibo

  DOI：10.1021/jm00001a016

  日期：1995.1

  The influence of the 3-substituent on the cytotoxicity of the 6-aziridinylpyrrolo[1,2-a]benzimidazole quinones (PBIs), the 6-acetamidopyrrolo[1,2-a]benzimidazole quinones (APBIs), and the 6-acetamidopyrrolo[1,2-a]benzimidazole iminoquinones (imino-APBIs) was investigated by comparing LC(50) mean graphs consisting of 60 cancer lines. Increasing lipophilicity of the 3-substituent of PBIs and APBIs increased the cytotoxicity specifically in melanoma cell lines. The 3-substituent does not influence DNA cleavage by reduced PBIs, except for the S-carbamate derivative which shows enhanced cleavage. This property of the 3-carbamate is rationalized in terms of the PBI major groove binding model. The imino-APBIs show enhanced cytotoxicity in melanoma and renal cancer cell lines; the correlation coefficient for log LC(50) VS log lipophilicity is 0.8 to 0.9. COMPARE correlations revealed that the PBIs are activated by DT-diaphorase but that the APBIs and imino-APBIs are inactivated by this enzyme. Thus the latter two agents are cytotoxic only as quinones. It was noted that APBIs possess a similar cytotoxic profile to three anthracycline analogues. This observation suggests mechanistic similarities between both types of cytotoxic agents. Major conclusions of this study pertain to the design of agents displaying cytotoxicity specifically against melanoma and renal cancers and to the use of 60-cell line mean graphs and COMPARE in cancer drug QSAR.