(S)-吗啉-3-羧酸盐酸盐 | 1187929-04-9

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (S)-吗啉-3-羧酸盐酸盐
• 中文别名: (S)-3-吗啉甲酸盐酸盐；(S)-3-吗啉基羧酸；S-3-吗啉甲酸盐酸盐
• 英文名称: (3S)-morpholine-3-carboxylic acid hydrochloride
• 英文别名: (S)-Morpholine-3-carboxylic acid hydrochloride；(3S)-morpholine-3-carboxylic acid;hydrochloride
• CAS: 1187929-04-9
• 化学式: C₅H₉NO₃*ClH
• 分子量: 167.592
• InChiKey: CWSLARZELUGARZ-WCCKRBBISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.52
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  58.6
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  (S)-吗啉-3-羧酸盐酸盐 、 (R)-methyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (S)-4-[(R)-6-(2-bromo-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-3,6-dihydro-pyrimidin-4-ylmethyl]-morpholine-3-carboxylic acid
  参考文献：
  名称：

  Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors

  摘要：

  Described herein are the discovery and structure activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of.analogue 12 (HAP_iR01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen' onding interactions with capsid protein and coordinated waters. The representative analogue 10 (HAP_R10) was extensively characterized in vitro (ADMET) and in vivo (mouse PK and PD) and subsequently selected for further devehipffientas oral anti-HBV infection agent.

  DOI：

  10.1021/acs.jmedchem.7b00083

文献信息

• [EN] PROCESS FOR THE PREPARATION OF 4-PHENYL-5-ALKOXYCARBONYL-2-THIAZOL-2-YL-1,4-DIHYDROPYRIMIDINE ANALOGUES<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ANALOGUES DE 4-PHÉNYL-5-ALCOXYCARBONYL-2-THIAZOL-2-YL-1,4-DIHYDROPYRIMIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2016102438A1

  公开（公告）日：2016-06-30

  The present invention relates to a process for synthesizing a compound of formula (I), (I), wherein R1 is phenyl, which is unsubstituted, or once, twice or three times substituted by halogen; R2 is C1-6alkyl; R3 is heterocyclyl; and diastereomer, pharmaceutically acceptable salts thereof, which is useful for prophylaxis and treatment of a viral disease in a patient relating to hepatitis B infection or a disease caused by hepatitis B infection.

  本发明涉及一种合成化合物的方法，该化合物的化学式为(I)，其中R1为苯基，未被取代，或者被卤素取代一次、两次或三次；R2为C1-6烷基；R3为杂环烷基；以及该化合物的对映体、药学上可接受的盐，用于预防和治疗与乙型肝炎感染有关的病毒疾病或由乙型肝炎感染引起的疾病的方法。
• A New Approach of Mitigating CYP3A4 Induction Led to the Discovery of Potent Hepatitis B Virus (HBV) Capsid Inhibitor with Optimal ADMET Profiles
  作者：Xianfeng Lin、Houguang Shi、Weixing Zhang、Zongxing Qiu、Zheng Zhou、Fabian Dey、Sheng Zhong、Hongxia Qiu、Jianxun Xie、Xue Zhou、Guang Yang、Guozhi Tang、Hong C. Shen、Wei Zhu

  DOI：10.1021/acs.jmedchem.9b01421

  日期：2019.11.27

  imidine (HAP) class of capsid inhibitors successfully altered the structure–activity−relationships (SARs) of the unwanted CYP3A4 induction and the desired HBV capsid inhibition to more favorable values. This eventually led to the discovery of a new capsid inhibitor with significantly reduced CYP3A4 induction, excellent anti-HBV activity, favorable preclinical PK/PD profiles, and no early safety flags

  本文描述了减轻CYP3A4诱导的新方法。在这种非常规方法中，C4苯基和杂芳基二氢嘧啶（HAP）类衣壳抑制剂的二氢嘧啶核之间的二面角微调成功地改变了不需要的CYP3A4诱导和所需的结构-活性-关系（SARs） HBV衣壳抑制达到更有利的值。这最终导致发现了一种新的衣壳抑制剂，该抑制剂具有显着降低的CYP3A4诱导作用，优异的抗HBV活性，有利的临床前PK / PD谱，且无早期安全性标志。
• [EN] DIHYDROPYRIMIDINE COMPOUND AND APPLICATION THEREOF<br/>[FR] COMPOSÉ DIHYDROPYRIMIDINE ET SON UTILISATION<br/>[ZH] 二氢嘧啶类化合物、其应用
  申请人：HEPAGENE THERAPEUTICS HK LTD

  公开号：WO2022052923A1

  公开（公告）日：2022-03-17

  提供了一种如式(I)所示的二氢嘧啶类化合物、其互变异构体或其药学上可接受的盐、及其应用。该二氢嘧啶类化合物具有较好的抗HBV活性，可用于制备治疗和/或预防HBV感染的药物。
• [EN] 6-SUBSTITUTED INDOLE COMPOUNDS<br/>[FR] COMPOSÉS INDOLES SUBSTITUÉS EN POSITION 6
  申请人：GILEAD SCIENCES INC

  公开号：WO2022140325A1

  公开（公告）日：2022-06-30

  The present disclosure relates generally to certain compounds, pharmaceutical compositions comprising said compounds, and methods of making and using said compounds and pharmaceutical compositions. The compounds and compositions provided herein may be used for the treatment or prevention of an autoimmune disease and/or inflammatory condition, including systemic lupus erythematosus and cutaneous lupus erythematosus.

  本公开涉及某些化合物、包含所述化合物的制药组合物以及制备和使用所述化合物和制药组合物的方法。本文提供的化合物和组合物可用于治疗或预防自身免疫性疾病和/或炎症病状，包括全身性红斑狼疮和皮肤型红斑狼疮。
• [EN] DIHYDROPYRIMIDINE DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS DE DIHYDROPYRIMIDINE ET LEUR UTILISATION<br/>[ZH] 二氢嘧啶衍生物及其用途
  申请人：HENAN TIANSHENG TAIFENG PHARMACEUTICAL TECH CO LTD

  公开号：WO2020001592A1

  公开（公告）日：2020-01-02

  本发明涉及通式(I)的二氢嘧啶类衍生物，它们可用于治疗和预防乙型肝炎病毒感染。本发明还涉及含有通式(I)化合物的药物组合物，及其用于治疗和预防乙型肝炎病毒感染的用途。