(2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-2-propan-2-ylnonanamide

• 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
• 英文名称: (2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-2-propan-2-ylnonanamide
• 英文别名: 5-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-2-propan-2-ylnonanamide
• 化学式: C₃₀H₅₃N₃O₆
• 分子量: 551.8
• InChiKey: UXOWGYHJODZGMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  39
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  146
• 氢给体数：
  4
• 氢受体数：
  7

文献信息

• [EN] FACTOR IXa INHIBITORS<br/>[FR] INHIBITEURS DE FACTEUR IXA
  申请人：MERCK SHARP & DOHME

  公开号：WO2014099694A1

  公开（公告）日：2014-06-26

  The present invention provides a compound of Formula (I) wherein A is a heterocycle ring system and B is a heterocycle ring system or aryl ring system, and pharmaceutical compositions comprising one or more of said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes.

  本发明提供了一种化合物，其化学式为（I），其中A是一个杂环环系统，B是一个杂环环系统或芳香环系统，以及包含一种或多种所述化合物的药物组合物，以及使用所述化合物用于治疗或预防血栓、栓塞、高凝血性或纤维变化的方法。
• 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。
• SUBSTITUTED BISPHENYL BUTANOIC ESTER DERIVATIVES AS NEP INHIBITORS
  申请人：NOVARTIS AG

  公开号：US20190240177A1

  公开（公告）日：2019-08-08

  The present disclosure provides a compound of Formula (I); or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are defined herein. The disclosure also relates to a method for manufacturing the compounds of the disclosure, and its therapeutic uses. The present disclosure further provides pharmaceutical composition of the compounds of the disclosure and a combination of pharmacologically active agents and a compound of the disclosure.

  本公开提供一种式（I）的化合物；或其药学上可接受的盐，其中R1和R2在此定义。本公开还涉及一种制造本公开化合物的方法，以及其治疗用途。本公开进一步提供本公开化合物的药物组合物和药理活性剂与本公开化合物的组合。
• Manufacturing process for 8-aryloctanoic acids such as Aliskiren
  申请人：SOUKUP MILAN

  公开号：US20120296100A1

  公开（公告）日：2012-11-22

  The present invention relates to a novel manufacturing process and novel intermediates useful in the synthesis of pharmaceutically active compound such as Aliskiren. The invention describes preparation of enantiomerically pure 8-aryloctanoic acid of formula I from a chiral compound of formula IV. Friedel-Crafts reaction of this compound of formula IV with a compound of formula III provides compound of formula II which is converted reductively in a few steps into the compound of formula V, a know intermediate in the synthesis of compound of formula I. According to the disclosed process, Aliskiren can be now prepared from commercial starting materials (Guajacol or 2-bromoanisole, cis- or trans-1,4-dichloro-2-butene and 4(S)-benzyl-3-isovaleroyl-oxazolidin-2-one) in less than 8 process steps.

  本发明涉及一种新型制造工艺和新型中间体，用于合成药用活性化合物如阿利司琼。该发明描述了从式IV手性化合物制备式I式的对映纯8-芳基辛酸的方法。将该式IV化合物与式III化合物进行弗里德尔-克拉夫茨反应，得到式II化合物，经过几个步骤还原转化为式V化合物，这是合成式I化合物的已知中间体。根据披露的工艺，现在可以从商业起始原料（愈创木酚或2-溴苯甲醚、顺式或反式-1,4-二氯-2-丁烯和4(S)-苄基-3-异戊酰氧唑啉-2-酮）中在不到8个步骤内制备阿利司琼。
• PREPARATION OF N-SUBSTITUTED 2,7-DIALKYL-4-HYDROXY-5-AMINO-8-ARYL-OCTANOYL AMIDES
  申请人：Herold Peter

  公开号：US20060041169A1

  公开（公告）日：2006-02-23

  From compounds of formula II wherein R 1 and R 2 are independently of one another H, C 1 -C 6 alkyl, C 1 -C 6 halogenalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkoxy-C 1 -C 6 alkyl, or C 1 -C 6 alkoxy-C 1 -C 6 alkyloxy, R 3 is C 1 -C 6 alkyl, and R 5 is C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 alkanoyloxy-C 1 -C 6 alkyl, C 1 -C 6 aminoalkyl, C 1 -C 6 alkylamino-C 1 -C 6 -alkyl, C 1 -C 6 -dialkylamino-C 1 -C 6 -alkyl, C 1 -C 6 -alkanoylamido-C 1 -C 6 -alkyl, HO(O)C—C 1 -C 6 -alkyl, C 1 -C 6 alkyl-O—(O)C—C 1 -C 6 alkyl, H 2 N—C(O)—C 1 -C 6 alkyl, C 1 -C 6 alkyl-HN—C(O)—C 1 -C 6 alkyl or (C 1 -C 6 alkyl) 2 N—C(O)—C 1 -C 6 -alkyl, R 6 is C 1 -C 6 alkyl, R 7 is C 1 -C 6 alkyl or C 1 -C 6 alkoxy, or R 6 and R 7 together are tetramethylene, pentamethylene, 3-oxa-1,5-pentylene or —CH 2 CH 2 O— substituted, if necessary, with C 1 -C 4 -Alkyl, phenyl or benzyl, it is possible—through halolactonization, azidation of the halogen group, ring opening with an amine R 5 —NH 2 , and reduction of the azide group to form the amino group—to prepare compounds of formula I wherein R 5 is C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkoxy-C 1 -C 6 alkyl, C 1 -C 6 alkanoyloxy-C 1 -C 6 alkyl, C 1 -C 6 aminoalkyl, C 1 -C 6 alkylamino-C 1 -C 6 alkyl, C 1 -C 6 dialkylamino-C 1 -C 6 alkanoylamido-C 1 -C 6 alkyl, HO(O)C—C 1 -C 6 alkyl, C 1 -C 6 alkyl-O—(O)C—C 1 -C 6 alkyl, H 2 N—C(O)—C 1 -C 6 alkyl, C 1 -C 6 alkyl-HN—C(O)—C 1 -C 6 alkyl or (C 1 -C 6 alkyl) 2 —N—C(O)—C 1 -C 6 alkyl. If 2(S),7(R)-diastereomer of formula II is used, the 2(S),4(S),5(S),7(S)-diastereomer of formula Ia is obtained in a high degree of purity.

  从公式II的化合物中，其中R1和R2分别是H、C1-C6烷基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6烷氧基-C1-C6烷基、或C1-C6烷氧基-C1-C6烷氧基，R3是C1-C6烷基，R5是C1-C6烷基、C1-C6羟基烷基、C1-C6烷氧基-C1-C6-烷基、C1-C6酰氧基-C1-C6烷基、C1-C6氨基烷基、C1-C6烷基氨基-C1-C6烷基、C1-C6二烷基氨基-C1-C6-烷基、C1-C6-酰胺基-C1-C6-烷基、HO（O）C—C1-C6-烷基、C1-C6烷氧基-O—（O）C—C1-C6-烷基、H2N—C（O）—C1-C6-烷基、C1-C6烷基-HN—C（O）—C1-C6-烷基或（C1-C6烷基）2N—C（O）—C1-C6-烷基，R6是C1-C6烷基，R7是C1-C6烷基或C1-C6烷氧基，或R6和R7一起是四亚甲基、五亚甲基、3-氧代-1,5-戊二烯或-CH2CH2O-取代，必要时用C1-C4烷基、苯基或苄基取代，可以通过卤代内酯化、卤素基的氮化、胺R5—NH2的环开放和氮化物基的还原形成氨基基团来制备公式I的化合物，其中R5是C1-C6烷基、C1-C6羟基烷基、C1-C6烷氧基-C1-C6烷基、C1-C6酰氧基-C1-C6烷基、C1-C6氨基烷基、C1-C6烷基氨基-C1-C6烷基、C1-C6二烷基氨基-C1-C6-烷基、C1-C6-酰胺基-C1-C6-烷基、HO（O）C—C1-C6-烷基、C1-C6烷氧基-O—（O）C—C1-C6-烷基、 —C（O）—C1-C6-烷基、C1-C6烷基-HN—C（O）—C1-C6-烷基或（C1-C6烷基）2—N—C（O）—C1-C6-烷基。如果使用公式II的2（S），7（R）-对映异构体，则可以获得公式I的2（S），4（S），5（S），7（S）-对映异构体，其纯度高。