C-benzo[1,2,5]oxadiazol-5-yl-methylamine | 321330-19-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶二唑类
• 英文名称: C-benzo[1,2,5]oxadiazol-5-yl-methylamine
• 英文别名: 2,1,3-Benzoxadiazole-5-methanamine；2,1,3-benzoxadiazol-5-ylmethanamine
• CAS: 321330-19-2
• 化学式: C₇H₇N₃O
• mdl: MFCD03086104
• 分子量: 149.152
• InChiKey: SJBQXDAJQLKGKC-UHFFFAOYSA-N

物化性质

• 沸点：
  276.3±32.0 °C(Predicted)
• 密度：
  1.322±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  64.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  C-benzo[1,2,5]oxadiazol-5-yl-methylamine 、 (3S,11aR)-6-(benzyloxy)-8-bromo-3-methyl-2,3,11,11a-tetrahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-5,7-dione 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 为溶剂， 反应 22.0h， 生成 (3S,11aR)-N-(benzo[c][1,2,5]oxadiazol-5-ylmethyl)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide
  参考文献：
  名称：

  新型整合酶链转移抑制剂（INSTI）的合成，生物学评估和计算机模拟。

  摘要：

  尽管目前有相对广泛的治疗选择可用于治疗HIV / AIDS，但它仍然是最严重和最致命的疾病之一，并且死亡率很高。整合酶链转移抑制剂（INSTI），例如FDA批准的dolutegravir（DTG），bictegravir（BIC）和cabo​​tegravir（CAB），最近已作为标准的高效抗逆转录病毒疗法（HAART）方案中的五种主要成分之一获得最有益的临床结果。在本文中，我们描述了包含杂芳族生物等位取代而不是经过充分研究的卤素取代的苄基片段的新型INSTI的组合酰胺合成，生物学评估和计算机模拟。着眼于上述多样性点，选择了中等大小的化合物文库进行合成。一项生物学研究表明，许多分子是高活性的INSTI（EC50 <10 nM）。两种化合物1 {4}和1 {26}表现出与CAB相当的皮摩尔抗病毒活性，并且比DTG和BIC更具活性。进行了分子对接研究以评估化合物在HIV-1 IN活性位点的结合模式。在大鼠中，铅化合物1

  DOI：

  10.1016/j.ejmech.2020.112064
• 作为产物：
  描述：

  5-(bromomethyl)benzofuroxan 生成 C-benzo[1,2,5]oxadiazol-5-yl-methylamine
  参考文献：
  名称：

  WO2007/71393

  摘要：

  公开号：

文献信息

• [EN] COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR<br/>[FR] COMPOSÉS ET MÉTHODES UTILISÉS POUR LA MODULATION DES KINASES ET INDICATIONS À CET EFFET
  申请人：PLEXXIKON INC

  公开号：WO2011063159A1

  公开（公告）日：2011-05-26

  Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.

  描述了化合物及其盐、配方、共轭物、衍生物、形式和用途。在某些方面和实施例中，所述化合物或其盐、配方、共轭物、衍生物、形式对至少一种Raf蛋白激酶具有活性。在某些方面和实施例中，所述化合物在抑制Ras突变细胞系增殖方面具有活性。还描述了使用这些方法来治疗疾病和病况，包括与B-Raf V600E突变蛋白激酶活性相关的疾病和病况，包括黑色素瘤、胶质瘤、胶质母细胞瘤、乳头状星形细胞瘤、结直肠癌、甲状腺癌、肺癌、卵巢癌、前列腺癌、肝癌、胆囊癌、胃肠间质瘤、胆道癌和胆管癌。还描述了使用这些方法来治疗与c-Raf-1蛋白激酶活性相关的疾病和病况，包括急性疼痛、慢性疼痛或多囊肾病。
• Pyridine matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20020161000A1

  公开（公告）日：2002-10-31

  Selective MMP-13 inhibitors are pyridine derivatives of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: R 1 and R 2 independently are hydrogen, halo, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, NO 2 , NR 4 R 5 , CN, or CF 3 , E is independently O or S; A and B independently are OR 4 or NR 4 R 5 ; R 4 and R 5 independently are H. C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (CH 2 ) n aryl, (CH 2 ) n cycloalkyl, (CH 2 ) n heteroaryl, or R 4 and R 5 when taken together with the nitrogen to which they are attached complete a 3 to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NH, and optionally substituted or unsubstituted, n is an integer of from 0 to 6.

  选择性MMP-13抑制剂是符合以下结构式1的吡啶衍生物或其药用盐，其中： R1和R2独立地是氢、卤素、羟基、C1-C6烷基、C1-C6烷氧基、C2-C6烯基、C2-C6炔基、NO2、NR4R5、CN或CF3； E独立地是O或S； A和B独立地是OR4或NR4R5； R4和R5独立地是H、C1-C6烷基、C2-C6烯基、C2-C6炔基、(CH2)n芳基、(CH2)n环烷基、(CH2)n杂环芳基，或者R4和R5当与它们连接的氮一起形成含碳原子的3至8元环，可选地含有O、S或NH等杂原子，并可选择性地取代或未取代； n是0到6的整数。
• Quinazolines as MMP-13 inhibitors
  申请人：——

  公开号：US20020193377A1

  公开（公告）日：2002-12-19

  A compound selected from those of formula (I): 1 in which: R 1 represents a group selected from hydrogen, amino, alkyl, alkenyl, aminoalkyl, aryl, arylalkyl, heterocycle, and cycloalkylalkyl, optionally substituted, W represents oxygen, sulfhur, or ═N—R′, in which R′ is as defined in the description, X 1 , X 2 and X 3 represent nitrogen or —C—R 6 in which R 6 is as defined in the description, Y represents oxygen, sulfhur, —NH, or —N(C 1 -C 6 )alkyl, Z represents oxygen, sulfhur, —NR 7 in which R 7 is as defined in the description, and 59 optionally carbon atom, n is an integer from 1 to 8 inclusive, Z 1 represents —CR 8 R 9 wherein R 8 and R 9 are as defined in the description, A represents aromatic or non-aromatic, heterocyclic or non-heterocyclic ring system, m is an integer from 0 to 7 inclusive, the group(s) R 2 is (are) is as defined in the description, R 3 represents hydrogen, alkyl, alkenyl, alkynyl, ot a group of formula: 2 in which Z 2 , B, R 5 , P and q are as defined in the description, optionally, the racemic forms thereof, isomers thereof, N-oxydes thereof, and the pharmaceutically acceptable salts thereof, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix metalloprotease.

  从以下化学式（I）中选择的一种化合物： 其中： R1代表从氢、氨基、烷基、烯基、氨基烷基、芳基、芳基烷基、杂环和环烷基烷基中选择的基团，可选择取代； W代表氧、硫或═N—R′，其中R′如描述中定义； X1、X2和X3代表氮或—C—R6，其中R6如描述中定义； Y代表氧、硫、—NH或—N（C1-C6）烷基； Z代表氧、硫、—NR7，其中R7如描述中定义，且可选地是碳原子； n为1到8之间的整数； Z1代表—CR8R9，其中R8和R9如描述中定义； A代表芳香或非芳香、杂环或非杂环环系统； m为0到7之间的整数； R2代表如描述中定义的基团； R3代表氢、烷基、烯基、炔基或化学式2中的基团： 其中Z2、B、R5、P和q如描述中定义； 可选地，它们的外消旋体、异构体、N-氧化物和药学上可接受的盐，以及含有它们的药物制剂，可用作特异性抑制剂13型基质金属蛋白酶。
• Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib
  申请人：——

  公开号：US20040019053A1

  公开（公告）日：2004-01-29

  This invention provides a combination, comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. The invention combination may also be further combined with other pharmaceutical agents depending on the disease being treated.

  该发明提供了一种组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐。该发明还提供了一种治疗对MMP-13和环氧合酶-2抑制敏感的疾病的方法，包括向患有这种疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐的组合物。该发明还提供了一种药物组合物，包括包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐的组合物，以及药用载体、稀释剂或赋形剂。该发明组合物还可以根据所治疗的疾病进一步与其他药物代理结合。
• Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib
  申请人：——

  公开号：US20040019054A1

  公开（公告）日：2004-01-29

  This invention provides a combination, comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a combination comprising an NSAID, or a pharmaceutically acceptable salt thereof, and an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-1 or cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof. The invention combinations may also be further combined with other pharmaceutical agents depending on the disease being treated.

  本发明提供一种组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐，但不包括司来昔布或瓦来昔布。本发明还提供一种治疗对MMP-13和环氧合酶-2抑制响应的疾病的方法，包括向患有该疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐的本发明组合物，但不包括司来昔布或瓦来昔布。本发明还提供一种药物组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐的本发明组合物，但不包括司来昔布或瓦来昔布，以及药用载体、稀释剂或赋形剂。本发明还提供一种组合物，包括NSAID或其药用盐，以及MMP-13的变构羧酸抑制剂或其药用盐。本发明还提供一种药物组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及NSAID或其药用盐的本发明组合物，以及药用载体、稀释剂或赋形剂。本发明还提供一种治疗对MMP-13和环氧合酶-1或环氧合酶-2抑制响应的疾病的方法，包括向患有该疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，以及NSAID或其药用盐的本发明组合物。根据所治疾病的不同，本发明组合物也可以与其他药物组合。