5-(1H-苯并[d]咪唑-2-基)-2-甲基苯胺 | 292644-33-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 5-(1H-苯并[d]咪唑-2-基)-2-甲基苯胺
• 英文名称: 5-(1H-benzo[d]imidazol-2-yl)-2-methylaniline
• 英文别名: 5(1H-benzoimidazol-2-yl)-2-methyl-phenylamine；5-(1H-Benzoimidazol-2-yl)-2-methyl-phenylamine；5-(1H-benzimidazol-2-yl)-2-methylaniline
• CAS: 292644-33-8
• 化学式: C₁₄H₁₃N₃
• mdl: MFCD00852063
• 分子量: 223.277
• InChiKey: NWYALKGHFGHBQP-UHFFFAOYSA-N

物化性质

• 沸点：
  478.0±55.0 °C(Predicted)
• 密度：
  1.247±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  54.7
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  3,4-(亚甲二氧基)苯甲基硫代异氰酸酯 、 5-(1H-苯并[d]咪唑-2-基)-2-甲基苯胺 以 丙酮 为溶剂， 反应 1.0h， 生成 1-(5-(1H-benzo[d]imidazol-2-yl)-2-methylphenyl)-3-(benzo[d][1,3]dioxol-5-ylmethyl)thiourea
  参考文献：
  名称：

  Synthesis and structure–activity relationship of non-peptidic antagonists of neuropilin-1 receptor

  摘要：

  Neuropilins (NRPs) are VEGF-A165 co-receptors over-expressed in tumor cells, and considered as targets in angiogenic-related pathologies. We previously identified compound 1, the first non-peptidic antagonist of the VEGF-A165/NRP binding, which exhibits in vivo anti-angiogenic and anti-tumor activities. We report here the synthesis and biological evaluations of new antagonists structurally-related to compound 1. Among these molecules, 4a, 4c and 4d show cytotoxic effects on HUVEC and MDA-MB-31 cells, and antagonize VEGF-A165/NRP-1 binding. This study confirmed our key structure-activity relationships hypothesis and paved the way to compound 1 'hit to lead' optimization.

  DOI：

  10.1016/j.bmcl.2014.07.028
• 作为产物：
  描述：

  2-(4-methyl-3-nitro-phenyl)-1H-benzimidazole 在 iron(III) chloride 肼 作用下， 以 甲醇 为溶剂， 反应 2.33h， 生成 5-(1H-苯并[d]咪唑-2-基)-2-甲基苯胺
  参考文献：
  名称：

  [EN] HETEROCYCLIC AMIDES USEFUL FOR THE TREATMENT OF CANCER AND PSORIASIS
  [FR] AMIDES HÉTÉROCYCLIQUES UTILES DANS LE TRAITEMENT DU CANCER ET DU PSORIASIS

  摘要：

  本公开涉及杂环酰胺化合物，这些化合物对抑制Hedgehog途径有用，并且它们在治疗由Hedgehog途径抑制单独或部分介导的疾病或医疗状况中的用途。还公开了这些化合物的制造方法，包括这些化合物的药物组合物，以及利用这些化合物制造用于治疗受试者中的这些疾病和医疗状况的药物的方法。公式（IA），条件是R2或R3中的一个是（Z）。

  公开号：

  WO2009027746A1

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS COMPRISING NEUROPILIN INHIBITORS, AND THEIR USE FOR THE PREVENTION AND/OR TREATMENT OF ANGIOGENIC DISORDERS AND CANCERS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES COMPRENANT DES INHIBITEURS DE NEUROPILINE, ET LEUR UTILISATION DANS LA PRÉVENTION ET/OU LE TRAITEMENT DE TROUBLES ANGIOGÉNIQUES ET DE CANCERS
  申请人：TRAGEX PHARMA

  公开号：WO2012156289A1

  公开（公告）日：2012-11-22

  The present invention relates to a compound of general formula (I), wherein Z1 is S or O, preferably S; -Z2- is -NRa-, wherein Ra is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, preferably Ra is H; -N=; O; S; -CRb=, wherein Rb is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F, preferably H; -CHRC- wherein Rc is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F, or -CH2-; preferably -Z2- is -NH- or -N=; each of R1 and R2 independently is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F; preferably R1 and R2 together and with N and Z2 form an heterocycle eventually substituted, provided that said heterocycle is not an indole; R5 is H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, preferably R5 is NH2, NO2, C1, F, Br, I; more preferably R5 is H or CH3; even more preferably R5 is CH3; each of R8 and R9 independently is, H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F; preferably R8 and R9 together form a cycle comprising 5 or 6 atoms, preferably an heterocycle comprising 5 or 6 atoms, more preferably a 1,3- dioxacyclopentene or a 1,4-dioxane; and - each of R3, R4, R6, R7, R10 and R11 independently is, H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, NO2, F, C1, Br, I; preferably H, CH3, OCH3, OH, NH2, NO2, C1, F, Br, I; more preferably is H or CH3; even more preferably is H; and to a pharmaceutical composition comprising a compound of general formula (I) or esters or salts thereof, in association with at least one pharmaceutically acceptable vehicle; and to the use thereof for inhibiting the Neuropilin pathways in the treatment of cancer and of angiogenic diseases.

  本发明涉及一般式(I)的化合物，其中Z1为S或O，优选为S；-Z2-为-NRa-，其中Ra为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺，优选Ra为H；-N=；O；S；-CRb=，其中Rb为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺、NO2、C1、Br、I、F，优选为H；-CHRC-，其中Rc为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺、NO2、C1、Br、I、F，或-CH2-；优选-Z2-为-NH-或-N=；R1和R2各自独立为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺、NO2、C1、Br、I、F，优选R1和R2一起与N和Z2形成最终可能被取代的杂环，前提是该杂环不是吲哚；R5为H、OH、C1-4烷基、C1-4烷氧基、C1-4烯基、C1-4炔基、胺，优选R5为NH2、NO2、C1、F、Br、I，更优选R5为H或CH3，甚至更优选R5为CH3；R8和R9各自独立为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺、NO2、C1、Br、I、F，优选R8和R9一起形成包括5或6个原子的环，优选为包括5或6个原子的杂环，更优选为1,3-二氧杂环戊烯或1,4-二氧杂环戊烷；每个R3、R4、R6、R7、R10和R11各自独立为H、OH、C1-4烷基、C1-4烷氧基、C1-4烯基、C1-4炔基、胺、NO2、F、C1、Br、I，优选为H、CH3、OCH3、OH、NH2、NO2、C1、F、Br、I，更优选为H或CH3，甚至更优选为H；以及包含一般式(I)的化合物或其酯或盐的药物组合物，与至少一种药用可接受载体结合使用，用于抑制神经丝蛋白途径，治疗癌症和血管生成性疾病。
• Pharmaceutical compositions comprising Neuropilin inhibitors, and their use for the prevention and/or treatment of angiogenic disorders and cancers
  申请人：Tragex Pharma

  公开号：EP2522341A1

  公开（公告）日：2012-11-14

  The present invention relates to a pharmaceutical composition comprising a compound of general formula (I), wherein - Z1 is S or O, preferably S; - -Z2- is -NRa-, wherein Ra is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, preferably Ra is H; -N=; O; S; -CRb=, wherein Rb is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, Cl, Br, I, F, preferably H; -CHRc-, wherein Rc is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, Cl, Br, I, F, or -CH2-; preferably -Z2- is -NH- or -N=; - each of R1 and R2 is independently H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, Cl, Br, I, F; preferably R1 and R2 together and with N and Z2 form an heterocycle eventually substituted, more preferably a substituted azocine, 3H-indole, indazole, 2-imidazoline, 2-pyrazoline, benzthiazole, purine, pyrimidine, pyridine, pyridazine, pyrazine, pyrazole, thiazole, isothiazole, oxazole, isoxazole, quinoline, isoquinoline, quinoxaline, quinazoline, 1-8-naphthyridine, perimidine, [1,10]-phenantroline, phthalazine, pteridine, triazole, triazine, furazan, 6H-1,2,5-thiadiazine, 1,3,4-thiadiazole, tetrazole, or a substituted imidazole and even more preferably a benzimidazole; - R5 is H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, preferably R5 is NH2, NO2, Cl, F, Br, I; more preferably R5 is H or CH3; even more preferably R5 is CH3; - each of R8 and R9 is independently, H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, Cl, Br, I, F; preferably R8 and R9 together form a cycle comprising 5 or 6 atoms, preferably an heterocycle comprising 5 or 6 atoms, more preferably a 1,3-dioxacyclopentene or a 1,4-dioxane; and - each of R3, R4, R6, R7, R10 and R11 is independently, H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, NO2, F, Cl, Br, I; preferably H, CH3, OCH3, OH, NH2, NO2, Cl, F, Br, I; more preferably is H or CH3; even more preferably is H, or esters or salts thereof; in association with at least one pharmaceutically acceptable vehicle; and to the use thereof for inhibiting the Neuropilin pathways in the treatment of cancer and of angiogenic diseases.

  本发明涉及一种包含一般式(I)化合物的药物组合物，其中- Z1为S或O，优选S；- -Z2-为-NRa-，其中Ra为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺，优选Ra为H；-N=；O；S；-CRb=，其中Rb为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺、NO2、Cl、Br、I、F，优选H；-CHRc-，其中Rc为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺、NO2、Cl、Br、I、F，或-CH2-；优选-Z2-为-NH-或-N=；- R1和R2中的每一个独立地为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺、NO2、Cl、Br、I、F；优选R1和R2连同N和Z2形成最终被取代的杂环，更优选为取代的氮杂环、3H-吲哚、吲哚唑、2-咪唑啉、2-吡唑啉、苯并噻唑、嘧啶、嘧啶、吡啶、吡啶啉、吡啶二唑、吡啶啉、噻唑、异噻唑、噁唑、异噁唑、喹啉、异喹啉、喹啉、1-8-萘啉、邻苯二嗪、邻苯二氮杂吡啉、邻苯二氮杂吡啉、[1,10]-邻菲啉、邻苯二甲酸咪唑啉、喹啉、三唑、三嗪、呋喃唑、6H-1,2,5-二噻二氮杂嗪、1,3,4-二噻二唑、四唑，或取代的咪唑并且更优选为苯并咪唑；- R5为H、OH、C1-4烷基、C1-4烷氧基、C1-4烯基、C1-4炔基、胺，优选R5为NH2、NO2、Cl、F、Br、I；更优选R5为H或CH3；甚至更优选R5为CH3；- R8和R9中的每一个独立地为H、OH、烷基、烷氧基、芳基、烯基、炔基、胺、NO2、Cl、Br、I、F；优选R8和R9连同形成包含5或6个原子的环，优选为包含5或6个原子的杂环，更优选为1,3-二氧杂环戊烯或1,4-二氧杂环戊烷；- R3、R4、R6、R7、R10和R11中的每一个独立地为H、OH、C1-4烷基、C1-4烷氧基、C1-4烯基、C1-4炔基、胺、NO2、F、Cl、Br、I；优选H、CH3、OCH3、OH、NH2、NO2、Cl、F、Br、I；更优选为H或CH3；甚至更优选为H，或其酯或盐；与至少一种药学上可接受的载体结合；以及将其用于抑制神经丝蛋白途径在癌症和血管生成性疾病治疗中的应用。
• TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY
  申请人：Wynne Graham Michael

  公开号：US20090075938A1

  公开（公告）日：2009-03-19

  There are disclosed compound of Formula (1): A 1 , A 2 , A 3 and A 4 which may be the same or different, represent N or CR 1 , X is a divalent group selected from O, S(O) n , C═W, NR 4 , NC(═O)R 5 and CR 6 R 7 , W is O, S, NR 20 , Y is N or CR 8 , one of R 4 , R 5 , R 6 , R 8 , R 9 and NR 20 represents -L-R 3 , in which L is a single bond or a linker group, additionally, R 1 , R 3 -R 9 , which may be the same or different, independently represent hydrogen or a substituent and R 20 represents hydrogen, hydroxyl, alkyl optionally substituted by aryl, alkoxy optionally substituted by aryl, aryl, CN, optionally substituted alkoxy, optionally substituted aryloxy, optionally substitute alkanoyl, optionally substituted aroyl, NO 2 , NR 30 R 31 , in which R 30 and R 31 , which may be the same or different, represent hydrogen, optionally substituted alkyl or optionally substituted aryl; additionally, one of R 30 and R 31 may represent optionally substituted alkanoyl or optionally substituted aroyl, n represents an integer from 0 to 2, in addition, when an adjacent pair of A 1 -A 4 each represent CR 1 , then the adjacent carbon atoms, together with their substituents may form a ring B, when X is CR 6 R 7 , R 6 and R 7 , together with the carbon atom to which they are attached may form a ring C, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the therapeutic and/or prophylactic treatment of Duchenne muscular dystrophy, Becker muscular dystrophy or cachexia.

  公式（1）的化合物被揭示：A1，A2，A3和A4，它们可以相同或不同，代表N或CR1，X是从O，S（O）n，C═W，NR4，NC（═O）R5和CR6R7中选择的二价基团，W是O，S，NR20，Y是N或CR8，R4，R5，R6，R8，R9和NR20中的一个表示-L-R3，在其中L是单键或连接基团，此外，R1，R3-R9可以相同或不同，独立地表示氢或取代基，R20表示氢，羟基，可以用芳基取代的烷基，可以用芳基取代的烷氧基，芳基，CN，可以用芳基取代的烷氧基，可以用芳基取代的芳氧基，可以用取代基取代的烷酰基，可以用取代基取代的芳酰基，NO2，NR30R31，在其中R30和R31可以相同或不同，表示氢，可选地取代的烷基或可选地取代的芳基；此外，R30和R31中的一个可以表示可选地取代的烷酰基或可选地取代的芳酰基，n表示从0到2的整数，另外，当相邻的A1-A4中的一对表示CR1时，那么相邻的碳原子及其取代基可以形成环B，当X为CR6R7时，R6和R7与它们附着的碳原子一起可以形成环C，或其药学上可接受的盐，在制造用于治疗和/或预防杜氏肌萎缩症，贝克肌萎缩症或消瘦症的药物时使用。
• Drug Combinations for the Treatment of Duchenne Muscular Dystrophy
  申请人：Wynne Graham Michael

  公开号：US20110195932A1

  公开（公告）日：2011-08-11

  Combinations comprising (or consisting essentially of) one or more compounds of formula (1) with one or more ancillary agents, to processes for preparing the combinations, and to various therapeutic uses of the combinations. Also provided are pharmaceutical compositions containing the combinations as well as a method of treatment of Duchenne muscular dystrophy, Becker muscular dystrophy or cachexia using the combinations.

  本发明涉及与一种或多种化合物（1）的一个或多个辅助剂组合的组合物，以制备这些组合物的过程，以及这些组合物的各种治疗用途。还提供了包含这些组合物的制药组合物，以及使用这些组合物治疗杜氏肌营养不良症、贝克肌营养不良症或消瘦的方法。
• PHARMACEUTICAL COMPOSITIONS COMPRISING NEUROPILIN INHIBITORS, AND THEIR USE FOR THE PREVENTION AND/OR TREATMENT OF ANGIOGENIC DISORDERS AND CANCERS
  申请人：TRAGEX PHARMA

  公开号：US20130041005A1

  公开（公告）日：2013-02-14

  The present invention relates to a compound of general formula (I), and to a pharmaceutical composition comprising a compound of general formula (I) or esters or salts thereof, in association with at least one pharmaceutically acceptable vehicle; and to the use thereof for inhibiting the Neuropilin pathways in the treatment of cancer and of angiogenic diseases.

  本发明涉及一种通式(I)的化合物，以及包含通式(I)的化合物或其酯或盐与至少一种药用载体结合的制药组合物；以及在抑制神经粘附蛋白途径治疗癌症和血管生成性疾病方面的应用。