5-chloro-2,3-dihydro-1H-inden-2-amine | 73536-83-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5-chloro-2,3-dihydro-1H-inden-2-amine
• CAS: 73536-83-1
• 化学式: C₉H₁₀ClN
• mdl: MFCD13190211
• 分子量: 167.638
• InChiKey: KBMVAIAEDLKXCX-UHFFFAOYSA-N

物化性质

• 沸点：
  261.5±40.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5-chloro-2,3-dihydro-1H-inden-2-amine 在 盐酸 、 三乙胺 作用下， 以 氯仿 、 溶剂黄146 为溶剂， 反应 12.0h， 生成 (S)-5-chloro-2,3-dihydro-1H-inden-2-amine
  参考文献：
  名称：

  A Novel Approach for the Development of Selective Cdk4 Inhibitors:  Library Design Based on Locations of Cdk4 Specific Amino Acid Residues

  摘要：

  Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding pattern. To address this issue, we applied the following structure-based approach for designing selective Cdk4 inhibitors: (1) identification of specifically altered amino acid residues around the ATP binding pocket in Cdk4 by comparison of 390 representative kinases, (2) prediction of appropriate positions to introduce substituents in lead compounds based on the locations of the altered amino acid residues and the binding modes of lead compounds, and (3) library design to interact with the altered amino acid residues supported by de novo design programs. Accordingly, Asp99, Thr102, and Gln98 of Cdk4, which are located in the p16 binding region, were selected as first target residues for specific interactions with Cdk4. Subsequently, the 5-position of the pyrazole ring in the pyrazol-3-ylurea class of lead compound (2a) was predicted to be a suitable position to introduce substituents. We then designed a chemical library of pyrazol-3-ylurea substituted with alkylaminomethyl groups based on the output structures of de novo design programs. Thus we identified a highly selective and potent Cdk4 inhibitor, 15b, substituted with a 5-chloroindan-2-ylaminomethyl group. Compound 15b showed higher selectivity on Cdk4 over those on not only Cdk1/2 (780-fold/190-fold) but also many other kinases (> 430-fold) that have been tested thus far. The structural basis for Cdk4 selective inhibition by 15b was analyzed by combining molecular modeling and the X-ray analysis of the Cdk4 mimic Cdk2-inhibitor complex. The results suggest that the hydrogen bond with the carboxyl group of Asp99 and hydrophobic van der Waals contact with the side chains of Thr102 and Gln98 are important. Compound 15b was found to cause cell cycle arrest of the Rb(+) cancer cell line in the G(1) phase, indicating that it is a good biological tool.

  DOI：

  10.1021/jm010326y
• 作为产物：
  描述：

  2-氨基茚 在 氯 、 溶剂黄146 作用下， 反应 0.25h， 生成 5-chloro-2,3-dihydro-1H-inden-2-amine
  参考文献：
  名称：

  A Novel Approach for the Development of Selective Cdk4 Inhibitors:  Library Design Based on Locations of Cdk4 Specific Amino Acid Residues

  摘要：

  Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding pattern. To address this issue, we applied the following structure-based approach for designing selective Cdk4 inhibitors: (1) identification of specifically altered amino acid residues around the ATP binding pocket in Cdk4 by comparison of 390 representative kinases, (2) prediction of appropriate positions to introduce substituents in lead compounds based on the locations of the altered amino acid residues and the binding modes of lead compounds, and (3) library design to interact with the altered amino acid residues supported by de novo design programs. Accordingly, Asp99, Thr102, and Gln98 of Cdk4, which are located in the p16 binding region, were selected as first target residues for specific interactions with Cdk4. Subsequently, the 5-position of the pyrazole ring in the pyrazol-3-ylurea class of lead compound (2a) was predicted to be a suitable position to introduce substituents. We then designed a chemical library of pyrazol-3-ylurea substituted with alkylaminomethyl groups based on the output structures of de novo design programs. Thus we identified a highly selective and potent Cdk4 inhibitor, 15b, substituted with a 5-chloroindan-2-ylaminomethyl group. Compound 15b showed higher selectivity on Cdk4 over those on not only Cdk1/2 (780-fold/190-fold) but also many other kinases (> 430-fold) that have been tested thus far. The structural basis for Cdk4 selective inhibition by 15b was analyzed by combining molecular modeling and the X-ray analysis of the Cdk4 mimic Cdk2-inhibitor complex. The results suggest that the hydrogen bond with the carboxyl group of Asp99 and hydrophobic van der Waals contact with the side chains of Thr102 and Gln98 are important. Compound 15b was found to cause cell cycle arrest of the Rb(+) cancer cell line in the G(1) phase, indicating that it is a good biological tool.

  DOI：

  10.1021/jm010326y

文献信息

• Dihydro-indene-amine-dihydrooxazoles
  申请人：Beecham Group plc

  公开号：US04861789A1

  公开（公告）日：1989-08-29

  A compound of formula (I): ##STR1## or a pharmaceutically acceptable acid addition salt and/or a pharmaceutically acceptable solvate thereof, wherein A represents a residue of a benzene ring optionally having up to four substituents selected from the group consisting of halogen, C.sub.1-6 alkyl aNd C.sub.1-6 alkoxy; R.sup.1 and R.sup.2 each independently represent a hydrogen atom or a C.sub.1-6 alkyl group; X represents a bond or a moiety CHR.sup.1 wherein R.sup.1 is as defined above; and Z represents O, NH or S.

  化合物的化学式（I）：##STR1## 或其药用可接受的酸盐和/或药用可接受的溶剂化合物，其中A代表苯环的残基，可选择具有最多四个取代基，所选自卤素、C.sub.1-6烷基和C.sub.1-6烷氧基；R.sup.1和R.sup.2各自独立地代表氢原子或C.sub.1-6烷基基团；X代表键或基团CHR.sup.1，其中R.sup.1如上所定义；Z代表O、NH或S。
• [EN] 6-SUBSTITUTED PHENOXYCHROMAN CARBOXYLIC ACID DERIVATIVES<br/>[FR] DÉRIVÉS DE L'ACIDE CARBOXYLIQUE PHÉNOXYCHROMANE SUBSTITUÉS EN 6
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2009158426A1

  公开（公告）日：2009-12-30

  Compounds of Formula (I): in which A1, A2, W, L, G, R7a, R7b, R8, R9 and R10 have the meanings given in the specification, are DP2 receptor modulators useful in the treatment of immunologic diseases.

  式（I）的化合物：其中A1、A2、W、L、G、R7a、R7b、R8、R9和R10具有规范中给定的含义，是DP2受体调节剂，可用于治疗免疫性疾病。
• [EN] AMINOAZINE AMIDES<br/>[FR] AMIDES D'AMINOAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2020123426A1

  公开（公告）日：2020-06-18

  The disclosure provides novel compounds having the general formula (I) or a pharmaceutically acceptable salt, solvate or salt of the solvate thereof, compositions including the compounds and methods of using the compounds.

  该披露提供了具有一般式(I)或其药用可接受盐、溶剂或其溶剂盐的新化合物，包括这些化合物的组合物以及使用这些化合物的方法。
• [EN] CYCLIC PYRIDYL-N-(1,3,4)-THIADIAZOL-2-YL-BENZENE SULFONAMIDES, PROCESSES FOR THEIR PREPARATION AND THEIR USE AS PHARMACEUTICALS<br/>[FR] PYRIDYL-N-(1,3,4)-THIADIAZOL-2-YL-BENZÈNESULFONAMIDES CYCLIQUES, LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION COMME PRODUITS PHARMACEUTIQUES
  申请人：SANOFI AVENTIS

  公开号：WO2009080223A1

  公开（公告）日：2009-07-02

  The invention relates to cyclic N-[1,3,4]-thiadiazol-2-yl-benzene sulfonamides and to their physiologically acceptable salts and physiologically functional derivatives showing PPARdelta or PPARdelta and PPARgamma agonist activity. What is described are compounds of the Formula (I), in which the radicals are as defined, and their physiologically acceptable salts and processes for their preparations. The compounds are suitable for the treatment and/or prevention of disorders of fatty acid metabolism and glucose utilization disorders as well as of disorders in which insulin resistance is involved and demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.

  该发明涉及环状N-[1,3,4]-噻二唑-2-基苯磺酰胺及其生理上可接受的盐和生理功能衍生物，显示出PPARδ或PPARδ和PPARγ激动剂活性。所描述的是Formula (I)的化合物，其中基团如所定义，并且它们的生理上可接受的盐及其制备方法。这些化合物适用于治疗和/或预防脂肪酸代谢障碍和葡萄糖利用障碍，以及胰岛素抵抗相关的疾病，以及中枢和外周神经系统的脱髓鞘化和其他神经退行性疾病。
• [EN] INHIBITING USP36<br/>[FR] INHIBITION DE USP36
  申请人：INTEGRAL EARLY DISCOVERY INC

  公开号：WO2020223548A1

  公开（公告）日：2020-11-05

  The present disclosure is directed to compounds of formulas (I) - (VI), which are useful as modulators of USP36. The compounds are further useful in the inhibition of USP36 and the treatment of diseases or disorders associated with the inhibition of USP36. For instance, the disclosure is concerned with compounds and compositions for inhibition of USP36, methods of treating diseases associated with the inhibition of USP36 (e.g., certain forms of cancer), and methods of synthesis of these compounds.

  本公开涉及的化合物具有(I) - (VI)的结构式，可用作USP36的调节剂。这些化合物进一步用于抑制USP36并治疗与USP36抑制相关的疾病或疾病。例如，本公开涉及用于抑制USP36的化合物和组合物，治疗与USP36抑制相关的疾病的方法（例如，某些癌症形式），以及这些化合物的合成方法。