5-Chloro-2-[3-(4-chloro-phenyl)-2-methylsulfanyl-propionylamino]-benzoic acid | 868526-86-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-Chloro-2-[3-(4-chloro-phenyl)-2-methylsulfanyl-propionylamino]-benzoic acid
• 英文别名: 5-Chloro-2-[3-(4-chlorophenyl)-2-methylsulfanyl-propionylamino]benzoic acid；5-chloro-2-[[3-(4-chlorophenyl)-2-methylsulfanylpropanoyl]amino]benzoic acid
• CAS: 868526-86-7
• 化学式: C₁₇H₁₅Cl₂NO₃S
• 分子量: 384.283
• InChiKey: GWLCCOWVBUEMSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-Chloro-2-[3-(4-chloro-phenyl)-2-methylsulfanyl-propionylamino]-benzoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以74%的产率得到6-chloro-2-[2-(4-chlorophenyl)-1-methylsulfanylethyl]benzo[d][1,3]oxazin-4-one
  参考文献：
  名称：

  Use of Structure-Based Drug Design Approaches to Obtain Novel Anthranilic Acid Acyl Carrier Protein Synthase Inhibitors

  摘要：

  Acyl carrier protein synthase (AcpS) catalyzes the transfer of the 4'-phosphopantetheinyl group from the coenzyme A to a serine residue in acyl carrier protein (ACP), thereby activating ACP, an important step in cell wall biosynthesis. The structure-based design of novel anthranilic acid inhibitors of AcpS, a potential antibacterial target, is presented. An initial high-throughput screening lead and numerous analogues were modeled into the available AcpS X-ray structure, opportunities for synthetic modification were identified, and an iterative process of synthetic modification, X-ray complex structure determination with AcpS, biological testing, and further modeling ultimately led to potent inhibitors of the enzyme. Four X-ray complex structures of representative anthranilic acid ligands bound to AcpS are described in detail.

  DOI：

  10.1021/jm050523n
• 作为产物：
  描述：

  5-chloro-2-[3-(4-chlorophenyl)-2-methylsulfanylpropionylamino]benzoic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以57%的产率得到5-Chloro-2-[3-(4-chloro-phenyl)-2-methylsulfanyl-propionylamino]-benzoic acid
  参考文献：
  名称：

  Use of Structure-Based Drug Design Approaches to Obtain Novel Anthranilic Acid Acyl Carrier Protein Synthase Inhibitors

  摘要：

  Acyl carrier protein synthase (AcpS) catalyzes the transfer of the 4'-phosphopantetheinyl group from the coenzyme A to a serine residue in acyl carrier protein (ACP), thereby activating ACP, an important step in cell wall biosynthesis. The structure-based design of novel anthranilic acid inhibitors of AcpS, a potential antibacterial target, is presented. An initial high-throughput screening lead and numerous analogues were modeled into the available AcpS X-ray structure, opportunities for synthetic modification were identified, and an iterative process of synthetic modification, X-ray complex structure determination with AcpS, biological testing, and further modeling ultimately led to potent inhibitors of the enzyme. Four X-ray complex structures of representative anthranilic acid ligands bound to AcpS are described in detail.

  DOI：

  10.1021/jm050523n

文献信息

• Inhibitors of phosphoglycerate dehydrogenase (PHGDH) and uses thereof
  申请人：Whitehead Institute for Biomedical Research

  公开号：US11225469B2

  公开（公告）日：2022-01-18

  The present invention provides compounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.

  本发明提供了式(II)化合物及其药学上可接受的盐、溶液剂、水合物、多晶型、共晶体、同分异构体、立体异构体、同位素标记的衍生物、原药及其组合物。还提供了涉及式(I)、(II)或(III)化合物的方法和试剂盒，用于治疗与受试者体内磷酸甘油脱氢酶（PHGDH）过度表达有关的疾病，如增殖性疾病（如癌症（如乳腺癌、ER阴性乳腺癌、黑色素瘤、宫颈癌）、良性肿瘤、与血管生成有关的疾病、炎症性疾病、自身炎症性疾病和自身免疫性疾病）。使用本发明的化合物或组合物治疗增殖性疾病患者，可抑制 PHGDH 的活性或抑制丝氨酸生物合成途径，或两者兼而有之。
• INHIBITORS OF PHOSPHOGLYCERATE DEHYDROGENASE (PHGDH) AND USES THEREOF
  申请人：Whitehead Institute for Biomedical Research

  公开号：US20180105508A1

  公开（公告）日：2018-04-19

  The present invention provides compounds pounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.