methyl (3S)-1,2-diazinane-3-carboxylate dihydrochloride

• 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: methyl (3S)-1,2-diazinane-3-carboxylate dihydrochloride
• 英文别名: Methyl (S)-Hexahydropyridazine-3-carboxylate Hydrochloride；methyl (3S)-diazinane-3-carboxylate;hydrochloride
• 化学式: C₆H₁₂N₂O₂*2ClH
• 分子量: 217.095
• InChiKey: SKHQENDPKXVMIR-JEDNCBNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.16
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  50.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (3S)-1,2-diazinane-3-carboxylate dihydrochloride 、 2-((S)-2-(((benzyloxy)carbonyl)(methyl)amino)-3-methylbutanamido)-3-(4-((R)-3-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-1-ethyl-2-(2-((S)-1-methoxyethyl)pyridin-3-yl)-1H-indol-5-yl)-1,1-dioxidothiomorpholin-2-yl)propanoic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以96 %的产率得到(3S)-methyl 1-(2-((S)-2-(((benzyloxy)carbonyl)(methyl)amino)-3-methylbutanamido)-3-(4-((R)-3-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-1-ethyl-2-(2-((S)-1-methoxyethyl)pyridin-3-yl)-1H-indol-5-yl)-1,1-dioxidothiomorpholin-2-yl)propanoyl)hexahydropyridazine-3-carboxylate
  参考文献：
  名称：

  [EN] METHODS FOR INHIBITING RAS
  [FR] PROCÉDÉS D'INHIBITION DE RAS

  摘要：

  该披露涉及抑制RAS蛋白的方法。该披露还包含治疗癌症的方法。

  公开号：

  WO2022251292A1

文献信息

• Caspase inhibitors and uses thereof
  申请人：——

  公开号：US20020045623A1

  公开（公告）日：2002-04-18

  This invention provides novel caspase inhibitors of formula I: 1 wherein R 1 is hydrogen, CHN 2 , R, or —CH 2 Y; R is an aliphatic group, an aryl group, an aralkyl group, a heterocyclyl group, or a heterocyclylalkyl group; Y is an electronegative leaving group; R 2 is CO 2 H, CH 2 CO 2 H, or esters, amides or isosteres thereof; X 2 —X 1 is N(R 3 )—C(R 3 ), C(R 3 ) 2 —C(R 3 ), C(R 3 ) 2 —N, N═C, C(R 3 )═C, C(═O)—N, or C(═O)—C(R 3 ); each R 3 is independently selected from hydrogen or C 16 aliphatic; Ring C is a fused aryl ring; n is 0, 1 or 2; and each methylene carbon in Ring A is optionally and independently substituted by ═O, or one or more halogen, C 1-4 alkyl, or C 1-4 alkoxy. The compounds are useful for treating caspase-mediated diseases.

  本发明提供了新型的caspase抑制剂，其化学式为I：1，其中R1为氢、CHN2、R或—CH2Y；R为脂肪基、芳基、芳基烷基、杂环基或杂环基烷基；Y为电负性离去基；R2为CO2H、CH2CO2H或其酯、酰胺或同分异构体；X2—X1为N(R3)—C(R3)、C(R3)2—C(R3)、C(R3)2—N、N═C、C(R3)═C、C(═O)—N或C(═O)—C(R3)；每个R3独立选择自氢或C16脂肪基；环C为融合的芳基环；n为0、1或2；环A中的每个亚甲基碳原子可以选择性地且独立地被═O或一个或多个卤素、C1-4烷基或C1-4烷氧基取代。这些化合物对于治疗caspase介导的疾病是有用的。
• CAPASE INHIBITORS AND USES THEREOF
  申请人：Charrier Jean-Damien

  公开号：US20090023739A1

  公开（公告）日：2009-01-22

  This invention provides novel caspase inhibitors of formula I: wherein R 1 is hydrogen, CHN 2 , R, or —CH 2 Y; R is an aliphatic group, an aryl group, an aralkyl group, a heterocyclyl group, or a heterocyclylalkyl group; Y is an electronegative leaving group; R 2 is CO 2 H, CH 2 CO 2 H, or esters, amides or isosteres thereof; X 2 —X 1 is N(R 3 )—C(R 3 ), C(R 3 ) 2 —C(R 3 ), C(R 3 ) 2 —N, N═C, C(R 3 )═C, C(═O)—N, or C(═O)—C(R 3 ); each R 3 is independently selected from hydrogen or C 1-6 aliphatic; Ring C is a fused aryl ring; n is 0, 1 or 2; and each methylene carbon in Ring A is optionally and independently substituted by ═O, or one or more halogen, C 1-4 alkyl, or C 1-4 alkoxy. The compounds are useful for treating caspase-mediated diseases.

  本发明提供了一种新颖的caspase抑制剂，其化学式为I：其中R1为氢、CHN2、R或—CH2Y；R为脂肪基、芳基、芳基烷基、杂环基或杂环基烷基；Y为电负性离去基团；R2为CO2H、CH2CO2H或其酯、酰胺或同分异构体；X2—X1为N(R3)—C(R3)、C(R3)2—C(R3)、C(R3)2—N、N═C、C(R3)═C、C(═O)—N或C(═O)—C(R3)；每个R3独立地选择自氢或C1-6脂肪基；环C为融合的芳基环；n为0、1或2；环A中的每个亚甲基碳原子可选且独立地被═O、一个或多个卤素、C1-4烷基或C1-4烷氧基取代。这些化合物可用于治疗caspase介导的疾病。
• Caspase Inhibitors and Uses Thereof
  申请人：Charrier Jean-Damien

  公开号：US20110003824A1

  公开（公告）日：2011-01-06

  This invention provides novel caspase inhibitors of formula I: wherein R 1 is hydrogen, CHN 2 , R, or —CH 2 Y; R is an aliphatic group, an aryl group, an aralkyl group, a heterocyclyl group, or a heterocyclylalkyl group; Y is an electronegative leaving group; R 2 is CO 2 H, CH 2 CO 2 H, or esters, amides or isosteres thereof; X 2 -X 1 is N(R 3 )—C(R 3 ), C(R 3 ) 2 —C(R 3 ), C(R 3 ) 2 —N, N═C, C(R 3 )═C, C(═O)—N, or C(═O)—C(R 3 ); each R 3 is independently selected from hydrogen or C 1-6 aliphatic; Ring C is a fused aryl ring; n is 0, 1 or 2; and each methylene carbon in Ring A is optionally and independently substituted by ═O, or one or more halogen, C 1-4 alkyl, or C 1-4 alkoxy. The compounds are useful for treating caspase-mediated diseases.

  本发明提供了式I的新型caspase抑制剂： 其中，R1是氢，CHN2，R或—CH2Y; R是脂肪基团，芳基团，芳基烷基团，杂环基团或杂环基烷基团; Y是电负性离去基团; R2是CO2H，CH2CO2H或其酯，酰胺或异构体; X2-X1是N（R3）—C（R3），C（R3）2—C（R3），C（R3）2—N，N═C，C（R3）═C，C（═O）—N或C（═O）—C（R3）; 每个R3独立地选择自氢或C1-6脂肪基; 环C是螺合芳基环; n为0、1或2; 环A中的每个亚甲基碳原子可以选择性地且独立地被═O或一个或多个卤素、C1-4烷基或C1-4烷氧基取代。这些化合物可用于治疗caspase介导的疾病。
• [EN] METHODS FOR INHIBITING RAS<br/>[FR] PROCÉDÉS D'INHIBITION DE RAS
  申请人：REVOLUTION MEDICINES INC

  公开号：WO2022251292A1

  公开（公告）日：2022-12-01

  The disclosure features methods for inhibiting RAS proteins. The disclosure also contains methods for the treatment of cancer.

  该披露涉及抑制RAS蛋白的方法。该披露还包含治疗癌症的方法。
• [EN] HALOINDOLE MACROCYCLIC COMPOUNDS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS MACROCYCLIQUES HALOINDOLES POUR LE TRAITEMENT DU CANCER
  申请人：HOFFMANN LA ROCHE

  公开号：WO2023232776A1

  公开（公告）日：2023-12-07

  The present invention relates to compounds of formula (I), wherein R1to R7, A1and A2are as described herein, and their pharmaceutically acceptable salt thereof, and compositions including the compounds and methods of using the compounds.

  本发明涉及式（I）化合物（其中 R1 至 R7、A1 和 A2 如本文所述）及其药学上可接受的盐，以及包括该化合物的组合物和使用该化合物的方法。