(S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanoic acid | 1263819-22-2

• 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: (S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanoic acid
• 英文别名: (2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanamido]-3-methylbutanoic acid；Maleimidocaproyl valine；(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methylbutanoic acid
• CAS: 1263819-22-2
• 化学式: C₁₅H₂₂N₂O₅
• 分子量: 310.35
• InChiKey: OKLMYGIYGMPXPN-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanoic acid 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)propanamido)benzyl (4-nitrophenyl)carbonate
  参考文献：
  名称：

  NOVEL CAMPTOTHECIN DERIVATVES AS ANTIBODY-DRUG CONJUGATES (ADC) PAYLOADS

  摘要：

  The present invention describes novel camptothecin derivatives and methods for preparing camptothecin derivative payloads bearing a linker with a functional group that can be used for conjugation to cell binding agents to generate cytotoxic drug conjugates. The present invention further relates to antibody drug conjugates made with camptothecin derivative payloads bearing a linker moiety conjugated to tumor associated antigen (TAA) antibody, preparation methods, pharmaceutical compositions and uses thereof for the treatment of cancer. Methods relating to the use of the novel ADCs to treat antigen positive cells in cancers and immunological disorders are also provided herein.

  公开号：

  WO2024050031A2
• 作为产物：
  描述：

  L-缬氨酸叔丁酯盐酸盐 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 5.0h， 生成 (S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanoic acid
  参考文献：
  名称：

  [EN] ENEDIYNE COMPOUNDS, CONJUGATES THEREOF, AND USES AND METHODS THEREFOR
  [FR] COMPOSÉS D'ÈNEDIYNE, LEURS CONJUGUÉS AINSI QU'UTILISATIONS ET PROCÉDÉS S'Y RATTACHANT

  摘要：

  具有如下式（I）所示结构的恩二烯化合物，其中R0、R2、R3、R4、R5、R6和R7如本文所定义，可用于化疗药物，特别是在联合物中，用于治疗癌症等疾病。

  公开号：

  WO2013122823A1

文献信息

• [EN] FUNCTIONALIZED MORPHOLINYL ANTHRACYCLINE DERIVATIVES<br/>[FR] DÉRIVÉS DE MORPHOLINYLANTHRACYCLINE FONCTIONNALISÉS
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2016071418A1

  公开（公告）日：2016-05-12

  The present invention relates to new functionalized morpholinyl anthracycline derivatives which have cytotoxic activity and are useful in treating diseases such as cancer, cellular proliferation disorders and viral infections. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising them and methods of treating diseases utilizing such compounds, or the pharmaceutical compositions containing them. The invention also relates to the use of these derivatives in the preparation of conjugates. The morpholinyl anthracycline derivatives are of the formula Ant-L-W-Z-RM (I) wherein RM is null or a reactive moiety; Z is null or a peptidic, non peptidic or hybrid - peptidic and non peptidic - linker; W is null or a self-immolative system, comprising one or more self-immolative groups; L is null or a conditionally-cleavable moiety; Ant is an anthracycline moiety selected from the formulas (II), (III), (IV) and (V), wherein the wavy line indicates the attachment to the conditionally-cleavable moiety L, or to the self-immolative system W, or to the linker Z, or to the reactive moiety RM; provided that at least one of L, W, Z and RM is not null; R1 is halogen or NR4R5; R2 is OR6, NR7R8 or an optionally substituted group selected from straight or branched C1C4alkyl-, NR7R8-C1C4alkyl- and R60-C1C4alkyl-; R4 and R5 are independently hydrogen, a monosubstituted-benzyl, a disubstituted-benzyl, or an optionally substituted group selected from straight or branched C1-C6alkyl, NR7R8-C1-C6alkyl-, R60-C1-C6alkyl-, R7R8N-C1-C6alkylcarbonyl-, R60-C1-C6alkylcarbonyl-, R7R8N-C1-C6alkoxycarbonyl- and R60-C1-C6alkoxycarbonyl-; or R4 and R5, taken together with the nitrogen atom to which they are bound, form a heterocyclyl substituted with R4', wherein R4' is hydrogen or a group selected from straight or branched C1-C6alkyl and NR7R8-C1-C6alkyl-; R15 is null or an optionally substituted bivalent group selected from -NR7-C1-C6alkyl*, -O-C1-C6alkyl*, -NR7-C1-C6alkylcarbonyl*, -O-C1-C6alkylcarbonyl*, -NR7-C1-C6alkoxycarbonyl* and -O-C1-C6alkoxycarbonyl*, wherein * indicates the point of attachment to -NH-Ant; R6, R7 and R8 are independently hydrogen or an optionally substituted straight or branched C1-C6alkyl; or a pharmaceutically acceptable salt thereof.

  本发明涉及具有细胞毒活性并用于治疗癌症、细胞增殖紊乱和病毒感染等疾病的新功能化吗啉基蒽环素衍生物。本发明还提供了制备这些化合物的方法、包含它们的药物组合物以及利用这些化合物或含有它们的药物组合物治疗疾病的方法。该发明还涉及将这些衍生物用于制备共轭物的用途。吗啉基蒽环素衍生物的化学式为Ant-L-W-Z-RM（I），其中RM为空或为反应性基团；Z为空或为肽、非肽或混合肽和非肽连接物；W为空或为自解离系统，包括一个或多个自解离基团；L为空或为条件可切割基团；Ant为从化学式（II）、（III）、（IV）和（V）中选择的蒽环素基团，其中波浪线表示与条件可切割基团L、自解离系统W、连接物Z或反应性基团RM的连接；但要求至少有一个L、W、Z和RM不为空；R1为卤素或NR4R5；R2为OR6、NR7R8或从直链或支链C1-C4烷基、NR7R8-C1-C4烷基和R60-C1-C4烷基中选择的可选择取代基团；R4和R5独立地为氢、单取代苄基、双取代苄基或从直链或支链C1-C6烷基、NR7R8-C1-C6烷基、R60-C1-C6烷基、R7R8N-C1-C6烷基羰基、R60-C1-C6烷基羰基、R7R8N-C1-C6烷氧羰基和R60-C1-C6烷氧羰基中选择的可选择取代基团；或R4和R5与它们结合的氮原子一起形成与R4'取代的杂环烷基，其中R4'为氢或从直链或支链C1-C6烷基和NR7R8-C1-C6烷基中选择的基团；R15为空或从-NR7-C1-C6烷基*、-O-C1-C6烷基*、-NR7-C1-C6烷基羰基*、-O-C1-C6烷基羰基*、-NR7-C1-C6烷氧羰基*和-O-C1-C6烷氧羰基*中选择的可选择取代的二价基团，其中*表示与-NH-Ant的连接点；R6、R7和R8独立地为氢或可选择取代的直链或支链C1-C6烷基；或其药学上可接受的盐。
• [EN] NEODEGRADER CONJUGATES<br/>[FR] CONJUGUÉS DE TYPE NEODEGRADER
  申请人：ORUM THERAPEUTICS INC

  公开号：WO2021198965A1

  公开（公告）日：2021-10-07

  The present disclosure provides neoDegraders and neoDegraders conjugated to binding moieties. Also provided are compositions comprising the conjugates. The compounds and compositions are useful for treating a disease or condition, e.g., cancer, in a subject in need thereof.

  本公开提供了与结合基团结合的neoDegraders和neoDegraders。还提供了包含这些结合物的组合物。这些化合物和组合物对于治疗患有疾病或症状的受试者（例如癌症）是有用的。
• Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
  申请人：E. R. Squibb & Sons, L.L.C.

  公开号：US09226974B2

  公开（公告）日：2016-01-05

  Antiproliferative compounds having a structure represented by formula (II), where n, R1, R2, R3, R4, and R5 are as defined herein, can be used to treat tumors, optionally when conjugated to a ligand such as an antibody:

  具有由式(II)表示的结构的抗增殖化合物，其中n、R1、R2、R3、R4和R5如本文所定义，可用于治疗肿瘤，优选地当与配体（如抗体）偶联时使用。
• ENEDIYNE COMPOUNDS, CONJUGATES THEREOF, AND USES AND METHODS THEREFOR
  申请人：Bristol-Myers Squibb Company

  公开号：US20130209494A1

  公开（公告）日：2013-08-15

  Enediyne compounds having a structure according to formula (I), where R 0 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are defined herein, can be used in chemotherapeutic drugs, especially in conjugates, for the treatment of diseases such as cancer.

  恩二烯化合物具有如下式（I）所示的结构，其中R0、R2、R3、R4、R5、R6和R7的定义见本文，可用于化疗药物，特别是在共轭物中，用于治疗癌症等疾病。
• [EN] NEODEGRADER-ANTI-CD33 ANTIBODY CONJUGATES<br/>[FR] CONJUGUÉS NÉODÉGRADEUR-ANTICORPS ANTI-CD33
  申请人：ORUM THERAPEUTICS INC

  公开号：WO2022254377A1

  公开（公告）日：2022-12-08

  The present disclosure provides neoDegraders conjugated to anti-CD33 antibodies. Also provided are compositions comprising the conjugates. The compounds and compositions are useful for treating a disease or condition, e.g., cancer, in a subject in need thereof.

  本公开提供了与抗CD33抗体结合的neoDegraders。还提供了包括这些结合物的组合物。这些化合物和组合物可用于治疗需要治疗的主体的疾病或状况，例如癌症。