(2S)-N-[1-[[(2S,3R,4S)-1-环己基-3,4-二羟基-6-甲基庚烷-2-基]氨基]-1-氧代-3-(1,3-噻唑-4-基)丙-2-基]-2-[(4-甲基哌嗪-1-基)磺酰基甲基]-3-苯丙酰胺 | 138742-43-5

• 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: (2S)-N-[1-[[(2S,3R,4S)-1-环己基-3,4-二羟基-6-甲基庚烷-2-基]氨基]-1-氧代-3-(1,3-噻唑-4-基)丙-2-基]-2-[(4-甲基哌嗪-1-基)磺酰基甲基]-3-苯丙酰胺
• 中文别名: 碘化二(二甲氨基)-甲基-(1,4,7,10-四氧杂-13-氮杂环十五碳-13-基)磷烷正离子；二乙醇胺夫西地
• 英文名称: zankiren
• 英文别名: (2S)-N-{2-benzyl-3-[(1-methylpiperazin-4-yl)sulfonyl]propionyl}-3-thiazol-4-yl-L-alanine amide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane；(2S)-2-benzyl-N-[(2S)-1-[[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]amino]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl]-3-(4-methylpiperazin-1-yl)sulfonylpropanamide
• CAS: 138742-43-5
• 化学式: C₃₅H₅₅N₅O₆S₂
• 分子量: 705.984
• InChiKey: YFDSDRDMDDGDFC-HOQQKOLYSA-N

物化性质

• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  48
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  189
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (Z)-methyl 2-(bromomethyl)-3-phenylacrylate 在 镍 五氯化磷 、 水 、 氢气 、 sodium sulfite 作用下， 以 甲醇 、 水 、 丙酮 、 甲苯 为溶剂， 反应 72.0h， 生成 (2S)-N-[1-[[(2S,3R,4S)-1-环己基-3,4-二羟基-6-甲基庚烷-2-基]氨基]-1-氧代-3-(1,3-噻唑-4-基)丙-2-基]-2-[(4-甲基哌嗪-1-基)磺酰基甲基]-3-苯丙酰胺
  参考文献：
  名称：

  Enzyme-catalyzed synthesis of optically Pure β-sulfonamidopropionic acids. Useful starting materials for P-3 site modified renin inhibitors.

  摘要：

  The novel and efficient preparation of several racemic beta-sulfonamidopropionate esters is described. Treatment of the racemic esters with Chymotrypsin or Subtilisin Carlsberg (purified or detergent grade) provided the corresponding (S)-carboxylic acids in 60-90% yield. These acids (75 to >98 % e.e.) are useful starting materials for the synthesis of P-3 site modified renin inhibitors.

  DOI：

  10.1016/0040-4039(93)85095-e

文献信息

• Novel Heterocyclic Derivatives and Their Use in the Treatment of Neurological Disorders
  申请人：BADIGER Sangamesh

  公开号：US20120184539A1

  公开（公告）日：2012-07-19

  The invention relates to novel heterocyclic compounds of the formula in which all of the variables are as defined in the specification, pharmaceutical compositions thereof, combinations thereof, and their use as medicaments, particularly for the treatment of Alzheimer's Disease or diabetes via inhibition of BACE-1 or BACE-2.

  这项发明涉及公式的新异环化合物 其中所有变量均如规范中定义，其药物组成物，其组合物，以及它们作为药物的用途，特别是用于通过抑制BACE-1或BACE-2治疗阿尔茨海默病或糖尿病。
• [EN] ARYLPYRAZOLES AND ARYLISOXAZOLES AND THEIR USE AS PKD MODULATORS<br/>[FR] ARYLPYRAZOLES ET ARYLISOXAZOLES ET LEUR UTILISATION EN TANT QUE MODULATEURS DE LA PROTÉINE KINASE C (PKD)
  申请人：NOVARTIS AG

  公开号：WO2011009484A1

  公开（公告）日：2011-01-27

  The present invention provides novel organic compounds of formula (I) or (Ia): which may be inhibitors of a selective subset of kinases belonging to the AGC or calmodulin kinase family, such as for example PKD-1/2/3, inhibitors of histone deacetylase (HDAC) phosphorylation, or inhibitors of other kinases. The selectivity of which would depend on the structural variation thereof, and for treatment of a disorder or disease mediated by those selected AGC or calmodulin family kinases. These organic compounds can be used to treat various PKD associated states such as heart failure, colorectal cancer, regulation of cell growth, autoimmune disorders, or hyperproliferative skin disorders.

  本发明提供了化学式(I)或(Ia)的新型有机化合物：这些化合物可能是AGC或钙调素激酶家族中的一部分激酶的抑制剂，例如PKD-1/2/3，组蛋白去乙酰化酶（HDAC）磷酸化的抑制剂，或其他激酶的抑制剂。其选择性取决于其结构变化，用于治疗由这些选定的AGC或钙调素家族激酶介导的疾病或疾病。这些有机化合物可用于治疗各种PKD相关状态，如心力衰竭、结直肠癌、细胞生长调节、自身免疫性疾病或过度增生性皮肤疾病。
• [EN] 2,4'-BIPYRIDINYL COMPOUNDS AS PROTEIN KINASE D INHIBITORS USEFUL FOR THE TREATMENT OF IA HEART FAILURE AND CANCER<br/>[FR] COMPOSÉS DE 2,4'-BIPYRIDINYLE COMME INHIBITEURS DE LA PROTÉINE KINASE D UTILES POUR LE TRAITEMENT DE L'INSUFFISANCE CARDIAQUE ET DU CANCER
  申请人：NOVARTIS AG

  公开号：WO2009150230A1

  公开（公告）日：2009-12-17

  The present invention provides novel organic compounds of Formula I: methods of use, and pharmaceutical compositions thereof.

  本发明提供了式I的新型有机化合物：其使用方法和药物组合物。
• CYCLIC TETRAMER COMPOUNDS AS PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) INHIBITORS FOR THE TREATMENT OF METABOLIC DISORDERS
  申请人：NOVARTIS AG

  公开号：US20200164024A1

  公开（公告）日：2020-05-28

  The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , R 1 , X 1 , X 2 , and X 3 are described herein.

  该披露涉及对PCSK9的抑制剂，用于治疗胆固醇脂质代谢以及其他PCSK9发挥作用的疾病，其化学式为(I)： 或其药用可接受的盐、水合物、溶剂合物、前药、立体异构体、N-氧化物或互变异构体，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、X1、X2和X3如本文所述。
• [EN] ARYL-PYRIDINE DERIVATIVES AS ALDOSTERONE SYNTHASE INHIBITORS<br/>[FR] DÉRIVÉS D'ARYL-PYRIDINE EN TANT QU'INHIBITEURS D'ALDOSTÉRONE SYNTHASE
  申请人：NOVARTIS AG

  公开号：WO2011061168A1

  公开（公告）日：2011-05-26

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5 and n are defined herein. The invention also relates to a method for manufacturing compounds of the invention, and their therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了式（I）的化合物或其药学上可接受的盐，其中R1、R2、R3、R4、R5和n在此处定义。该发明还涉及一种制造该发明化合物的方法，以及它们的治疗用途。本发明还提供了一种药理活性剂的组合和制药组合物。