1-chloro-3-o-tolyl-propan-2-one | 38694-33-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-chloro-3-o-tolyl-propan-2-one
• 英文别名: 1-Chlor-3-(o-methylphenyl)-propanon；1-Chloro-3-(2-methylphenyl)propan-2-one
• CAS: 38694-33-6
• 化学式: C₁₀H₁₁ClO
• 分子量: 182.65
• InChiKey: WLVGLKYQYWYFDX-UHFFFAOYSA-N

物化性质

• 沸点：
  267.4±20.0 °C(Predicted)
• 密度：
  1.116±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险类别：
  8
• 危险性防范说明：
  P501,P234,P264,P280,P390,P303+P361+P353,P301+P330+P331,P363,P304+P340+P310,P305+P351+P338+P310,P406,P405
• 危险品运输编号：
  3265
• 危险性描述：
  H314,H290
• 包装等级：
  II
• 储存条件：
  2-8°C，惰性气体

反应信息

• 作为反应物：
  描述：

  1-chloro-3-o-tolyl-propan-2-one 在 一水合肼 、 三乙胺 、 N,N'-羰基二咪唑 、 lithium hexamethyldisilazane 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 1-benzyl-4-[5-methyl-4-(2-methylphenyl)-1H-pyrazol-3-ylmethyl]piperazine
  参考文献：
  名称：

  Substituted pyrazoles as novel selective ligands for the human dopamine D 4 receptor

  摘要：

  Two novel series of 3-(heterocyclylmethyl)pyrazoles have been synthesised and evaluated as ligands for the human dopamine D-4 receptor. Compounds in series I (exemplified by 8k) have a phenyl ring joined to the 4-position of the pyrazole while those in series II (exemplified by 15j) have a 5-phenyl ring linked by a saturated chain to the 4-position of the pyrazole. Both series supplied compounds with excellent affinity for the human D-4 and good selectivity over other dopamine receptors. Excellent selectivity over calcium, sodium, and potassium ion channels was also achieved. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00134-5
• 作为产物：
  描述：

  在 盐酸 、 水 作用下， 以 乙醚 为溶剂， 生成 1-chloro-3-o-tolyl-propan-2-one
  参考文献：
  名称：

  Synthesis and biological activity of N4-phenylsubstituted-6-(2,4-dichloro phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as vascular endothelial growth factor receptor-2 inhibitors and antiangiogenic and antitumor agents

  摘要：

  A series of eight N-4-phenylsubstituted-6-(2,4-dichlorophenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines 8-15 were synthesized as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors with varied substitutions in the phenyl ring of the 4-anilino moiety. In addition, five N-4-phenylsubstituted-6-phenylmethylsubstituted-7H-pyrrolo[2,3-d]pyrimidin-4-amines 16-20 were synthesized to evaluate the importance of the 2-NH2 moiety for multiple receptor tyrosine kinase (RTK) inhibition. Cyclocondensation of alpha-halomethylbenzylketones with 2,6-diamino-4-hydroxypyrimidine afforded 2-amino-6-(2,4-dichlorophenylmethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one, 23 and reaction of alpha-bromomethylbenzylketones with ethylamidinoacetate followed by cyclocondensation with formamide afforded the 6-phenylmethylsubstituted-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-ones, 40-42, respectively. Chlorination of the 4-position and displacement with appropriate anilines afforded the target compounds 8-20. Compounds 8, 10 and 14 were potent VEGFR-2 inhibitors and were 100-fold, 40-fold and 8-fold more potent than the standard semaxanib, respectively. Previously synthesized multiple RTK inhibitor, 5 and the VEGFR-2 inhibitor 8 from this study, were chosen for further evaluation in a mouse orthotopic model of melanoma and showed significant inhibition of tumor growth, angiogenesis and metastasis. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.052

文献信息

• [EN] 5-ARYL-THIAZOL-2-YL-AMINE COMPOUNDS AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS 5-ARYL-THIAZOL -2-YL-AMINE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：CHARLES MARK DAVID

  公开号：WO2015025172A1

  公开（公告）日：2015-02-26

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 5-aryl-thiazol-2-yl-amine compounds of the following formula (I) (for convenience, collectively referred to herein as "5AT2A compounds"), which, inter alia, inhibit LIM kinase (LIMK) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit LIMK activity, and in the treatment of diseases and conditions that are mediated by LIMK, that are ameliorated by the inhibition of LIMK activity, etc., including proliferative conditions such as cancer (e.g., breast cancer, prostate cancer, melanoma, glioma, etc.), as well as vasodilation (including, e.g., hypertension, angina, cerebral vasospasm, and ischemia following subarachnoid hemorrhage), neurodegenerative disorders, atherosclerosis, fibrosis, and inflammatory diseases (including, e.g., Crohn's disease and chronic obstructive pulmonary disease (COPD)), and glaucoma (also known as ocular hypertension). (Formula (I))

  本发明一般涉及治疗化合物领域，更具体地涉及以下式(I)的某些5-芳基噻唑-2-基胺化合物（为方便起见，以下统称为“5AT2A化合物”），其中，这些化合物等抑制LIM激酶（LIMK）活性。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物和组合物，无论是体外还是体内，来抑制LIMK活性，并在治疗由LIMK介导的疾病和症状中发挥作用，这些疾病和症状通过抑制LIMK活性得到改善，等等，包括增生性疾病，如癌症（例如乳腺癌、前列腺癌、黑色素瘤、胶质瘤等），以及血管舒张（包括高血压、心绞痛、脑血管痉挛以及蛛网膜下腔出血后的缺血），神经退行性疾病、动脉粥样硬化、纤维化和炎症性疾病（包括克罗恩病和慢性阻塞性肺病（COPD）等），以及青光眼（也称为眼压增高）。
• THIAZOLOPYRIMIDINONE COMPOUNDS AND PREPARATION METHODS AND USE THEREOF
  申请人：PEKING UNIVERSITY

  公开号：US20180155366A1

  公开（公告）日：2018-06-07

  The present invention provides structural details of a thiazolopyrimidinone compound, a preparation method thereof, and use thereof in the manufacture of a medicament for the treatment of central nervous system diseases.

  本发明提供了一种噻唑吡咯啉酮化合物的结构细节，其制备方法以及在制造用于治疗中枢神经系统疾病的药物中的应用。
• [EN] ISOXAZOLE AND PYRAZOLE DERIVATIVES AS DOPAMINE RECEPTOR SUBTYPE LIGANDS<br/>[FR] DERIVES D'ISOXAZOLE ET DE PYRAZOLE EN TANT QUE LIGANDS DE SOUS-TYPES DE RECEPTEURS DE LA DOPAMINE
  申请人：MERCK SHARP & DOHME LIMITED

  公开号：WO1995014672A1

  公开（公告）日：1995-06-01

  (EN) A class of substituted isoxazole and pyrazole derivatives of formula (I), or a salt thereof or a prodrug thereof, wherein the broken circle represents two non-adjacent double bonds whereby the five-membered ring containing X and Y is aromatic; one of X and Y represents nitrogen, and the other of X and Y represents oxygen or N-R5; R1 represents hydrogen, C1-6 alkyl or trifluoromethyl; R2 and R3 independently represent hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, nitro, -ORa, -SRa, -SORa, -SO2Ra, -SO2NRaRb, -NRaRb, -NRaCORb, -NRaCO2Rb, -CORa, -CO2Ra or -CONRaRb; R4 represents hydrocarbon or a heterocyclic group; R5 represents hydrogen or C1-6 alkyl; and Ra and Rb independently represent hydrogen, hydrocarbon or a heterocyclic group, are ligands for dopamine receptor subtypes within the body and are therefore useful in the treatment and/or prevention of disorders of the dopamine system, in particular schizophrenia.(FR) L'invention se rapporte à une classe de dérivés d'isoxazole et de pyrazole substitués de la formule (I), ou à un sel de ces dérivés ou à un promédicament les contenant. Dans cette formule, le cercle en pointillé représente deux doubles liaisons non adjacentes grâce auxquelles le noyau à cinq éléments contenant X et Y est aromatique; un des éléments X et Y représente azote, et l'autre représente oxygène ou N-R5; R1 représente hydrogène, alkyle C1-6 ou trifluorométhyle; R2 et R3 représentent indépendamment hydrogène, hydrocarbure, un groupe hétérocyclique, halogène, cyano, trifluorométhyle, nitro, -ORa, -SRa, -SORa, -SO2Ra, -SO2NRaRb, -NRaRb, -NRaCORb, -NRaCO2Rb, -CORa, -CO2Ra ou -CONRaRb; R4 représente hydrocarbure ou un groupe hétérocyclique; R5 représente hydrogène ou alkyle C1-6; et Ra et Rb représentent indépendamment hydrogène, hydrocarbure ou un groupe hétérocyclique. Ces dérivés sont des ligands de sous-types de récepteurs de la dopamine agissant dans le corps humain et sont par conséquent utiles dans le traitement et/ou la prévention de troubles du système dopamine, notamment de la schizophrénie.

  本发明涉及一类亚恶唑和吡唑衍生物，其通式为(I)，或这些衍生物的盐或前药。其中虚线圆环代表两个非相邻双键，使得含有X和Y的五元环是芳香族的；X和Y之一代表氮原子，另一者代表氧原子或N-R5；R1表示氢、C1-6烷基或三氟甲基；R2和R3各自独立地表示氢、烃类、杂环基团、卤素、氰基、三氟甲基、硝基、-ORa、-SRa、-SORa、-SO2Ra、-SO2NRaRb、-NRaRb、-NRaCORb、-NRaCO2Rb、-CORa、-CO2Ra或-CONRaRb；R4表示烃类或杂环基团；R5表示氢或C1-6烷基；Ra和Rb各自独立地表示氢、烃类或杂环基团。这些衍生物是体内多巴胺受体亚型的配体，因此可用于治疗和/或预防多巴胺系统相关的疾病，特别是精神分裂症。
• ISOXAZOLE AND PYRAZOLE DERIVATIVES AS DOPAMINE RECEPTOR SUBTYPE LIGANDS
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0730582A1

  公开（公告）日：1996-09-11
• US5684006A
  申请人：——

  公开号：US5684006A

  公开（公告）日：1997-11-04