D-(R)-3-(3-chloro-4-methoxyphenyl)alanine | 212252-91-0

• 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: D-(R)-3-(3-chloro-4-methoxyphenyl)alanine
• 英文别名: D-3-(3-chloro-4-methoxyphenyl)alanine；3-Chloro-o-methyl-d-tyrosine；(2R)-2-amino-3-(3-chloro-4-methoxyphenyl)propanoic acid
• CAS: 212252-91-0
• 化学式: C₁₀H₁₂ClNO₃
• 分子量: 229.663
• InChiKey: FVFCTFGTAWTEIF-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  D-(R)-3-(3-chloro-4-methoxyphenyl)alanine 在 氢溴酸 、 苯酚 作用下， 反应 6.0h， 以69%的产率得到3-氯-D-酪氨酸
  参考文献：
  名称：

  新型隐藻霉素抗肿瘤剂：片段“ B”类似物的合成和细胞毒性。

  摘要：

  描述了新型隐藻霉素类似物6的通用合成方法。通过与未保护的氨基酸9进行初始偶联，然后将无环前体16脱保护/大分子内酰胺化，最后将苯乙烯7氧化，以三步法将关键的常见中间体N-羟基琥珀酰亚胺活性酯15转化为β-环氧化物6。 C7-C8β-环氧化物。评价了在片段“ B”中带有不同侧链的隐藻霉素苯乙烯7和β-环氧化物6的细胞毒活性。一般而言，β-环氧化合物6比相应的α-环氧化合物17和苯乙烯7更有效。β-环氧化合物6u具有3-Cl，4-（二甲基氨基），具有较强的活性，而苄基侧链是有效活性所必需的。苄基部分，是制备的最有效的细胞毒剂，IC（50）= 54 pM，

  DOI：

  10.1021/jm980706s
• 作为产物：
  描述：

  3-氯-D-酪氨酸 、 硫酸二甲酯 在 sodium hydroxide 、 硫化氢 、 copper(II) sulfate 作用下， 生成 D-(R)-3-(3-chloro-4-methoxyphenyl)alanine
  参考文献：
  名称：

  Total Structures of Cryptophycins, Potent Antitumor Depsipeptides from the Blue-Green Alga Nostoc sp. Strain GSV 224

  摘要：

  Cryptophycin (A,1), the major cytotoxin in the blue-green alga (cyanobacterium) Nostoc sp. GSV 224, shows excellent activity against solid tumors implanted in mice. This cyclic depsipeptide had previously been isolated from Nostoc sp. ATCC 53789 as an antifungal agent and its gross structure determined by researchers at Merck. The relative and absolute stereochemistry of this potentially important drug has now been established using a combination of chemical and spectral techniques. Six minor cryptophycins (B-G, 2-7) have also been isolated from GSV 224 and their total structures and cytotoxicities determined. Two types of cryptophycins are present in this alga, the major series possessing a monochlorinated L-O-methyltyrosine unit and the minor series possessing a nonchlorinated D-O-methyltyrosine unit. Structure-activity relationship (SAR) studies of the cryptophycins and several derivatives and degradation products (8-14) are described. Also presented are preliminary in vivo results far cryptophycin A against six solid tumors.

  DOI：

  10.1021/ja00090a020

文献信息

• MACROCYCLIZATION OF COMPOUNDS FROM SOLID SUPPORT USING THIOESTERASES
  申请人：Sherman David H.

  公开号：US20090111152A1

  公开（公告）日：2009-04-30

  A method of preparing macrocycles using solid support chemistry and thioesterases is disclosed. Also disclosed are novel macrocycles.

  本发明公开了一种使用固相支持化学和硫酯酶制备大环化合物的方法。同时还公开了新型大环化合物。
• TYROSINE HYDROXYLASE INHIBITORS FOR USE IN TREATING CANCER
  申请人：Tyme, Inc.

  公开号：EP3488848A1

  公开（公告）日：2019-05-29

  The invention relates to a pharmaceutical composition comprising: a tyrosine hydroxylase inhibitor; and melanin, a melanin promoter, or a combination thereof. The invention also relates to a tyrosine hydroxylase inhibitor that is a-methyl-DL-tyrosine for use in treating cancer. Pharmaceutical compositions and kits including a tyrosine hydroxylase inhibitor; melanin, a melanin promoter, or a combination thereof; a p450 3A4 promoter; and a leucine aminopeptidase inhibitor are also provided. Also provided is the treatment of cancer in a subject, comprising administering an effective amount of a tyrosine hydroxylase inhibitor, a melanin promoter, a p450 3A4 promoter, and a leucine aminopeptidase inhibitor to the subject in need thereof. Also provided are means of reducing cell proliferation in a subject comprising administering an effective amount of a tyrosine hydroxylase inhibitor, a melanin promoter, a p450 3A4 promoter, and a leucine aminopeptidase inhibitor to the subject in need thereof.

  本发明涉及一种药物组合物，其中包含：酪氨酸羟化酶抑制剂；黑色素、黑色素促进剂或其组合。本发明还涉及一种用于治疗癌症的 a-甲基-DL-酪氨酸酪氨酸羟化酶抑制剂。还提供了包括酪氨酸羟化酶抑制剂、黑色素、黑色素促进剂或其组合、p450 3A4 促进剂和亮氨酸氨肽酶抑制剂的药物组合物和试剂盒。还提供了治疗受试者癌症的方法，包括向有需要的受试者施用有效量的酪氨酸羟化酶抑制剂、黑色素促进剂、p450 3A4 促进剂和亮氨酸氨肽酶抑制剂。还提供了减少受试者细胞增殖的方法，包括向有需要的受试者施用有效量的酪氨酸羟化酶抑制剂、黑色素促进剂、p450 3A4 促进剂和亮氨酸氨肽酶抑制剂。
• TYROSINE HYDROXYLASE INHIBITOR FOR TREATING INTESTINAL HYPERPERMEABILITY
  申请人：Hoffman, Steve

  公开号：EP3750555A1

  公开（公告）日：2020-12-16

  The present invention provides methods, compositions, and kits for treating intestinal hyperpermeability in a subject in need thereof, including conditions such as hyperglycemia and underlying diseases such as diabetes, autism, fibromyalgia, inflam -matory bowel disease (IBD), graft versus host disease (GVHD), HIV/ AIDS, multiple organ dysfunction syndrome, irritable bowel syndrome (IBS), celiac disease, eczema, psoriasis, acute pancreatitis, Parkinson's disease, depression, chronic fatigue syndrome, asthma, multiple sclerosis, arthritis, ankylosing spondylitis, nonalcoholic fatty liver disease, alcoholic cirrhosis, environmental en -teropathy, or kwashiorkor.

  本发明提供了用于治疗有需要的受试者肠道高渗透性的方法、组合物和试剂盒，包括高血糖症等病症和糖尿病、自闭症、纤维肌痛、炎症性肠病（IBD）、移植物抗宿主疾病（GVHD）、艾滋病病毒/艾滋病、多器官功能障碍综合征、肠易激综合征（IBS）、乳糜泻、湿疹、牛皮癣、急性胰腺炎、帕金森病、抑郁症、慢性疲劳综合征、慢性胰腺炎、帕金森病等潜在疾病、多器官功能障碍综合征、肠易激综合征（IBS）、乳糜泻、湿疹、银屑病、急性胰腺炎、帕金森病、抑郁症、慢性疲劳综合征、哮喘、多发性硬化症、关节炎、强直性脊柱炎、非酒精性脂肪肝、酒精性肝硬化、环境性肝炎或卡瓦氏病。
• Pharmaceutical compositions and methods
  申请人：Tyme, Inc.

  公开号：US10010590B2

  公开（公告）日：2018-07-03

  Pharmaceutical compositions and kits including a tyrosine hydroxylase inhibitor; melanin, a melanin promoter, or a combination thereof; a p450 3A4 promoter; and a leucine aminopeptidase inhibitor are provided. Also provided are methods of treating cancer in a subject, comprising administering an effective amount of a tyrosine hydroxylase inhibitor, a melanin promoter, a p450 3A4 promoter, and a leucine aminopeptidase inhibitor to the subject in need thereof. Also provided are methods of reducing cell proliferation in a subject comprising administering an effective amount of a tyrosine hydroxylase inhibitor, a melanin promoter, a p450 3A4 promoter, and a leucine aminopeptidase inhibitor to the subject in need thereof.

  提供了包括酪氨酸羟化酶抑制剂、黑色素、黑色素促进剂或其组合、p450 3A4 促进剂和亮氨酸氨肽酶抑制剂的药物组合物和试剂盒。还提供了治疗受试者癌症的方法，包括向有需要的受试者施用有效量的酪氨酸羟化酶抑制剂、黑色素启动子、p450 3A4启动子和亮氨酸氨肽酶抑制剂。还提供了减少受试者细胞增殖的方法，包括向有需要的受试者施用有效量的酪氨酸羟化酶抑制剂、黑色素促进剂、p450 3A4 促进剂和亮氨酸氨肽酶抑制剂。
• Compositions and methods for treating intestinal hyperpermeability
  申请人：Hoffman Steven

  公开号：US10085959B2

  公开（公告）日：2018-10-02

  The present invention provides methods, compositions, and kits for treating intestinal hyperpermeability in a subject in need thereof, including conditions such as hyperglycemia and underlying diseases such as diabetes, autism, fibromyalgia, inflammatory bowel disease (IBD), graft versus host disease (GVHD), HIV/AIDS, multiple organ dysfunction syndrome, irritable bowel syndrome (IBS), celiac disease, eczema, psoriasis, acute pancreatitis, Parkinson's disease, depression, chronic fatigue syndrome, asthma, multiple sclerosis, arthritis, ankylosing spondylitis, nonalcoholic fatty liver disease, alcoholic cirrhosis, environmental enteropathy, or kwashiorkor.

  本发明提供了用于治疗有需要的受试者肠道高渗透性的方法、组合物和试剂盒，包括高血糖症等病症和糖尿病、自闭症、纤维肌痛、炎症性肠病（IBD）、移植物抗宿主病（GVHD）、艾滋病毒/艾滋病、多器官功能障碍综合征、肠易激综合征（IBS）、乳糜泻、湿疹、牛皮癣、急性胰腺炎、帕金森病、抑郁症、慢性疲劳综合征等潜在疾病、多器官功能障碍综合征、肠易激综合征 (IBS)、乳糜泻、湿疹、牛皮癣、急性胰腺炎、帕金森病、抑郁症、慢性疲劳综合征、哮喘、多发性硬化症、关节炎、强直性脊柱炎、非酒精性脂肪肝、酒精性肝硬化、环境性肠病或卡瓦氏病。