(R)-1-(3-(cyclopentyloxy)phenyl)ethan-1-amine hydrochloride | 1198223-03-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-1-(3-(cyclopentyloxy)phenyl)ethan-1-amine hydrochloride
• 英文别名: (R)-1-(3-(cyclopentyloxy)phenyl)ethanamine hydrochloride；(1R)-1-(3-cyclopentyloxyphenyl)ethanamine;hydrochloride
• CAS: 1198223-03-8
• 化学式: C₁₃H₁₉NO*ClH
• 分子量: 241.761
• InChiKey: CYVBLVQCGGRCBA-HNCPQSOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  35.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-1-(3-(cyclopentyloxy)phenyl)ethan-1-amine hydrochloride 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 (R)-3-chloro-N-(1-(3-(cyclopentyloxy)phenyl)ethyl)-N-(methoxymethyl)propane-1-sulfonamide
  参考文献：
  名称：

  Discovery of Highly Potent Human Deoxyuridine Triphosphatase Inhibitors Based on the Conformation Restriction Strategy

  摘要：

  Human deoxyuridine triphosphatase (dUTPase) inhibition is a promising approach to enhance the efficacy of thymidylate synthase (TS) inhibitor based chemotherapy. In this study, we describe the discovery of a novel class of human dUTPase inhibitors based on the conformation restriction strategy. On the basis of the X-ray cocrystal structure of dUTPase and its inhibitor compound 7, we designed and synthesized two conformation restricted analogues, i.e., compounds 8 and 9. These compounds exhibited increased in vitro potency compared with the parent compound 7. Further structure activity relationship (SAR) studies identified a compound 43 with the highest in vitro potency (IC50 = 39 nM, EC50 = 66 nM). Furthermore, compound 43 had a favorable oral PK profile and exhibited potent antitumor activity in combination with 5-fluorouracil (5-FU) in the MX-1 breast cancer xenograft model. These results suggested that a dUTPase inhibitor may have potential for clinical usage.

  DOI：

  10.1021/jm300416h
• 作为产物：
  描述：

  (S,E)-N-(3-(cyclopentyloxy)benzylidene)-2-methylpropane-2-sulfinamide 在 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 为溶剂， 反应 12.5h， 生成 (R)-1-(3-(cyclopentyloxy)phenyl)ethan-1-amine hydrochloride
  参考文献：
  名称：

  Discovery of Highly Potent Human Deoxyuridine Triphosphatase Inhibitors Based on the Conformation Restriction Strategy

  摘要：

  Human deoxyuridine triphosphatase (dUTPase) inhibition is a promising approach to enhance the efficacy of thymidylate synthase (TS) inhibitor based chemotherapy. In this study, we describe the discovery of a novel class of human dUTPase inhibitors based on the conformation restriction strategy. On the basis of the X-ray cocrystal structure of dUTPase and its inhibitor compound 7, we designed and synthesized two conformation restricted analogues, i.e., compounds 8 and 9. These compounds exhibited increased in vitro potency compared with the parent compound 7. Further structure activity relationship (SAR) studies identified a compound 43 with the highest in vitro potency (IC50 = 39 nM, EC50 = 66 nM). Furthermore, compound 43 had a favorable oral PK profile and exhibited potent antitumor activity in combination with 5-fluorouracil (5-FU) in the MX-1 breast cancer xenograft model. These results suggested that a dUTPase inhibitor may have potential for clinical usage.

  DOI：

  10.1021/jm300416h

文献信息

• ANTI-TUMOR EFFECT POTENTIATOR
  申请人：Fukuoka Masayoshi

  公开号：US20120225838A1

  公开（公告）日：2012-09-06

  There is provided an agent for potentiating the effects of an anti-tumor agent. An anti-tumor effect potentiator containing, as an active ingredient, a uracil compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: wherein X represents a C 1-5 alkylene group and one of methylene groups constituting the alkylene group is optionally substituted with an oxygen atom; R 1 represents a hydrogen atom or a C 1-6 alkyl group; R 2 represents a hydrogen atom or a halogen atom; and R 3 represents a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 3-6 cycloalkyl group, a (C 3-6 cycloalkyl) C 1-6 alkyl group, a halogeno-C 1-6 alkyl group or a saturated heterocyclic group.

  提供了一种用于增强抗肿瘤药物效果的药剂。 一种抗肿瘤效应增强剂，其包含以下式(I)所代表的尿嘧啶化合物或其药用可接受的盐作为活性成分： 其中X代表一个C1-5烷基基团，构成该烷基基团的亚甲基基团之一可以选择性地被氧原子取代； R1代表氢原子或一个C1-6烷基基团；R2代表氢原子或卤原子；R3代表一个C1-6烷基基团，一个C2-6烯基基团，一个C3-6环烷基基团，一个(C3-6环烷基)C1-6烷基基团，一个卤代C1-6烷基基团或一个饱和杂环基团。
• [EN] HYDANTOIN CONTAINING DEOXYURIDINE TRIPHOSPHATASE INHIBITORS<br/>[FR] HYDANTOÏNE CONTENANT DES INHIBITEURS DE LA DÉSOXYURIDINE TRIPHOSPHATASE
  申请人：CV6 THERAPEUTICS NI LTD

  公开号：WO2018098206A1

  公开（公告）日：2018-05-31

  Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

  提供的是dUTPase抑制剂，包含此类化合物的组合物以及使用此类化合物和组合物的方法。
• [EN] 6-MEMBERED URACIL ISOSTERES<br/>[FR] ISOSTÈRES D'URACILE À 6 CHAÎNONS
  申请人：CV6 THERAPEUTICS NI LTD

  公开号：WO2018098204A1

  公开（公告）日：2018-05-31

  Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

  本文件提供了dUTPase抑制剂，包含此类化合物的组合物以及使用此类化合物和组合物的方法。
• NOVEL URACIL COMPOUND OR SALT THEREOF HAVING HUMAN DEOXYURIDINE TRIPHOSPHATASE INHIBITORY ACTIVITY
  申请人：Fukuoka Masayoshi

  公开号：US20110082163A1

  公开（公告）日：2011-04-07

  Provided is a uracil compound or a salt thereof, which has potent human dUTPase inhibitory activity and is useful as, for example, an antitumor drug. A uracil compound represented by the general formula (I) or a salt thereof: wherein n represents an integer of 1 to 3; X represents a bond, an oxygen atom, a sulfur atom, or the like; Y represents a linear or branched alkylene group having 1 to 8 carbon atoms, or the like; and Z represents —SO 2 NR 1 R 2 or —NR 3 SO 2 —R 4 , wherein R 1 and R 2 each represent an alkyl group having 1 to 6 carbon atoms, an aralkyl group which is optionally substituted, or the like; R 3 represents an alkyl group having 1 to 6 carbon atoms, or the like; and R 4 represents an aromatic hydrocarbon group, an unsaturated heterocyclic group, or the like.

  提供了一种尿嘧啶化合物或其盐，具有强效的人类dUTPase抑制活性，可用作例如抗肿瘤药物。一种由通式（I）表示的尿嘧啶化合物或其盐：其中n表示1至3的整数；X表示键，氧原子，硫原子或类似物；Y表示具有1至8个碳原子的线性或支链烷基或类似物；Z表示—SO2NR1R2或—NR3SO2—R4，其中R1和R2分别表示具有1至6个碳原子的烷基，可选择取代的芳基烷基或类似物；R3表示具有1至6个碳原子的烷基或类似物；R4表示芳香族碳氢基，不饱和杂环基或类似物。
• NOVEL URACIL COMPOUND HAVING INHIBITORY ACTIVITY ON HUMAN DEOXYURIDINE TRIPHOSPHATASE OR SALT THEREOF
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：EP2295414A1

  公开（公告）日：2011-03-16

  Provided is a uracil compound or a salt thereof, which has potent human dUTPase inhibitory activity and is useful as, for example, an antitumor drug. A uracil compound represented by the general formula (I) or a salt thereof: wherein n represents an integer of 1 to 3; X represents a bond, an oxygen atom, a sulfur atom, or the like; Y represents a linear or branched alkylene group having 1 to 8 carbon atoms, or the like; and Z represents -SO2NR1R2 or -NR3SO2-R4, wherein R1 and R2 each represent an alkyl group having 1 to 6 carbon atoms, an aralkyl group which is optionally substituted, or the like; R3 represents an alkyl group having 1 to 6 carbon atoms, or the like; and R4 represents an aromatic hydrocarbon group, an unsaturated heterocyclic group, or the like.

  本文提供了一种尿嘧啶化合物或其盐，它具有强效的人类 dUTP 酶抑制活性，可用作抗肿瘤药物等。 一种由通式（I）代表的尿嘧啶化合物或其盐： 其中 n 代表 1 至 3 的整数；X 代表键、氧原子、硫原子或类似物；Y 代表具有 1 至 8 个碳原子的直链或支链亚烷基或类似物；Z 代表-SO2NR1R2 或-NR3SO2-R4，其中 R1 和 R2 分别代表具有 1 至 6 个碳原子的烷基、任选取代的芳烷基或类似基团；R3 代表具有 1 至 6 个碳原子的烷基或类似基团；R4 代表芳香烃基团、不饱和杂环基团或类似基团。