2(R)-[1(RS)-(tert.-butoxycarbonyl)-4-phenylbutyl]-3-methylbutyric acid | 228262-45-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: 2(R)-[1(RS)-(tert.-butoxycarbonyl)-4-phenylbutyl]-3-methylbutyric acid
• 英文别名: (2R)-3-[(2-methylpropan-2-yl)oxycarbonyl]-6-phenyl-2-propan-2-ylhexanoic acid
• CAS: 228262-45-1
• 化学式: C₂₀H₃₀O₄
• 分子量: 334.456
• InChiKey: SBFKFYAPPGVMTR-ZYMOGRSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (E)-2(R)-[1-(RS)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-3-methylbutyric acid 以 palladium on charcoal catalyst 、 乙醇 为溶剂， 生成 2(R)-[1(RS)-(tert.-butoxycarbonyl)-4-phenylbutyl]-3-methylbutyric acid
  参考文献：
  名称：

  Compounds as inhibitor of tumor necrosis factor alpha release

  摘要：

  该发明提供了以下结构的肼衍生物 其中R1是较低的烷基、较低的烯基、较低的环烷基、较低的环烷基-较低的烷基、芳基或芳基-较低的烷基；R2是从α-、β-、γ-或δ-(氨基、羟基或硫醇)羧酸衍生的酰基，其中氨基、羟基或硫醇基可选择性地被较低的烷基化，或氨基可选择性地被酰化、磺酰化或酰胺化，并且侧链中存在的任何官能团可选择性地被保护，或者是Het(CH2)mCO的结构；R3是氢、较低的烷基、卤代较低的烷基、氰基-较低的烷基、氨基-较低的烷基、羟基-较低的烷基、较低的烷氧基-较低的烷基、较低的烷氧羰基-较低的烷基、较低的环烷基-较低的烷基、芳基-较低的烷基、杂环烷基-较低的烷基、杂环烷基羰基-较低的烷基、较低的烯基、较低的炔基、较低的环烷基、芳基-较低的烯基、芳基或杂环烷基；R4是较低的烷基、较低的烯基、较低的环烷基、较低的环烷基-较低的烷基或X-芳基、X-杂环芳基或—(CH2)n—CH=CR5R6的结构；R5和R6一起是较低的烷基，其中一个CH2基可选择性地被杂原子取代；Het是杂环烷基；X是间隔基；m为0、1、2、3或4；n为1或2；它们的药学上可接受的盐抑制肿瘤坏死因子α(TNF-α)从细胞中释放。它们可用作药物，特别是用于治疗炎症和自身免疫性疾病、骨关节炎、呼吸道疾病、肿瘤、消瘦症、心血管疾病、发热、出血和败血症。

  公开号：

  US06239151B1

文献信息

• NOVEL METALLOPROTEINASE INHIBITORS
  申请人：FUJI YAKUHIN KOGYO KABUSHIKI KAISHA

  公开号：EP1038864A1

  公开（公告）日：2000-09-27

  Compounds having not only a high metalloproteinase inhibitory activity but also remarkably improved medicinal applicability in vivo (oral absorbability, etc.) and biological activities and thus being useful a drugs; intermediates in the process for producing the same; and a process for producing these compounds. Specifically, compounds represented by general formula (I) or salts thereof, useful in medicinal and/or veterinary compositions, in particular; metalloproteinase inhibitors inhibiting matrix metalloproteinases and tumor necrosis factor-α (TNF-α) convertase; wherein R1 represents hydrogen or a hydroxy-protective group; R2 represents hydrogen or an amino-protective group; R3, R7 and R8 represent each hydrogen, hydroxy, alkyl, etc.; R4 represents alkyl, arylalkyl, etc.; R5 and R6 are the same or different and each represents hydrogen, alkyl, cycloalkyl, etc.; and R9 represents hydrogen, hydroxy, amino, etc.

  不仅具有较高的金属蛋白酶抑制活性，而且具有明显改善的体内药用性（口服吸收性等）和生物活性，因而可用作药物的化合物；生产这些化合物的中间体；以及生产这些化合物的工艺。具体地说，通式(I)代表的化合物或其盐，可用于药物和/或兽药组合物，特别是；金属蛋白酶抑制剂，可抑制基质金属蛋白酶和肿瘤坏死因子-α（TNF-α）转化酶；其中 R1 代表氢或羟基保护基团；R2 代表氢或氨基保护基团；R3、R7 和 R8 分别代表氢、羟基、烷基等；R4 代表烷基、氨基保护基团、羟基、烷基等。R4 代表烷基、芳烷基等；R5 和 R6 相同或不同，各自代表氢、烷基、环烷基等；R9 代表氢、羟基、氨基等。
• NOVEL REMEDIES FOR ALLERGIC DISEASES
  申请人：FUJI YAKUHIN KOGYO KABUSHIKI KAISHA

  公开号：EP1101492A1

  公开（公告）日：2001-05-23

  Disclosed are anti-inflammatory agents, antiallergic agents, particularly prophylactically and/or therapeutically effective drugs for type I and/or IV allergic conditions, and further pharmaceutical drugs for prophylactically and/or therapeutically treating bronchial asthma, atopic diseases, etc. The inventive drugs comprising a prophylactically and/or therapeutically effective amount of a hydroxamic acid derivative are active in the prophylaxis and/or therapy of allergy, especially type I and/or IV allergy, etc. The drugs are active in prophylactically and/or therapeutically treating inflammation, rhinitis, conjunctivitis, bronchial asthma, atopic diseases (including dermatitis, enteritis, etc.), or allergic gastroenterocolitis (allergic inflammation in digestive tract). The application of such drugs leads to (A) reduction of cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages and monocytes) at a diseased site, and/or (B) alleviation of inflammatory symptoms caused by migration, infiltration or accumulation of cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages and monocytes) to (or at) the diseased site, (C) inhibition of pathophysiological functions in cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages, monocytes, Langerhans cell and dendritic cells), and/or (D) reducing the blood level or inhibiting the production, of antibodies, especially IgE. Accordingly, the drugs are useful in the prophylaxis and/or therapy of diseases, disorders or ill conditions at the site.

  本发明公开了抗炎剂、抗过敏剂，尤其是对 I 型和/或 IV 型过敏症具有预防和/或治疗效果的药物，以及用于预防和/或治疗支气管哮喘、特应性疾病等的进一步药物。包含预防和/或治疗有效量羟肟酸衍生物的本发明药物在预防和/或治疗过敏症，尤其是 I 型和/或 IV 型过敏症等方面具有活性。这些药物在预防和/或治疗炎症、鼻炎、结膜炎、支气管哮喘、特应性疾病（包括皮炎、肠炎等）或过敏性胃肠炎（消化道过敏性炎症）方面具有活性。使用这类药物可(A)减少患病部位的细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞和单核细胞），和/或(B)减轻细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞和单核细胞）迁移、浸润或积聚引起的炎症症状、(C) 抑制细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞、单核细胞、朗格汉斯细胞和树突状细胞）的病理生理功能，和/或 (D) 降低血液中抗体，尤其是 IgE 的水平或抑制其产生。因此，这些药物可用于预防和/或治疗该部位的疾病、失调或病症。
• HYDRAZINE DERIVATIVES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1089964B1

  公开（公告）日：2003-10-29
• US6239151B1
  申请人：——

  公开号：US6239151B1

  公开（公告）日：2001-05-29
• [EN] HYDRAZINE DERIVATIVES<br/>[FR] DERIVES D'HYDRAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2000000465A1

  公开（公告）日：2000-01-06

  The invention provides hydrazine derivatives of formula (I) wherein R1 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl; R2 is an acyl group derived from an α-, β-, η- or δ-(amino, hydroxy or thiol) carboxylic acid in which the amino, hydroxy or thiol group is optionally lower alkylated or the amino group is optionally acylated, sulphonylated or amidated and in which any functional group present in a side-chain is optionally protected, or a group of the formula Het(CH¿2?)mCO; R?3¿ is hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, lower cycloalkyl-lower alkyl, aryl-lower alkyl, heterocyclyl-lower alkyl, heterocyclylcarbonyl-lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl-lower alkenyl, aryl or heterocyclyl; R4 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl or a grouping of the formula X-aryl, X-heteroaryl or (CH¿2?)n-CH=CR?5R6; R5 and R6¿ together are lower alkylene in which one CH¿2? group is optionally replaced by a hetero atom; Het is heterocyclyl; X is a spacer group; m is 0, 1, 2, 3 or 4; and n is 1 or 2; and their pharmaceutically acceptable salts inhibit the release of tumour necrosis factor alpha (TNF-α) from cells. They can be used as medicaments, especially in the treatment of inflammatory and autoimmune diseases, osteoarthritis, respiratory diseases, tumours, cachexia, cardiovascular diseases, fever, haemorrhage and sepsis.