(R)-2-bromo-4-methylpentanoic acid | 42990-28-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-2-bromo-4-methylpentanoic acid
• 英文别名: (2R)-2-bromo-4-methylpentanoic acid
• CAS: 42990-28-3
• 化学式: C₆H₁₁BrO₂
• 分子量: 195.056
• InChiKey: NNFDHJQLIFECSR-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 包装等级：
  II
• 危险类别：
  8
• 危险性防范说明：
  P260,P264,P271,P280,P301+P330+P331,P303+P361+P353,P304+P340,P305+P351+P338,P310,P363,P403+P233,P405,P501
• 危险品运输编号：
  3265
• 危险性描述：
  H335,H314

反应信息

• 作为反应物：
  描述：

  (R)-2-bromo-4-methylpentanoic acid 在 tert-butoxide 、 对甲苯磺酸 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 17.0h， 生成 tert-butyl (2R)-1,2-dibenzyl 4-methylpentane-1,1,2-tricarboxylate
  参考文献：
  名称：

  Highly water-soluble matrix metalloproteinases inhibitors and their effects in a rat adjuvant-induced arthritis model

  摘要：

  A new series of succinate-based dual inhibitors against matrix metalloproteinases (MMPs) and tumor necrosis factor or. converting enzyme (TACE) possessing highly-water solubility was designed, synthesized, and evaluated for enzyme inhibition. Incorporating of acidic or basic functional groups at the P-2' position afforded sufficient water solubility without significant loss of inhibitory potencies. Compound 18e, which had a guanidino group at the P-2' position as the basic functional group, exhibited broad inhibition against target enzymes for a relatively long period in rat plasma (beta1(1/2): 2.0 h) after sc administration when compared with compounds possessing acidic functional groups (18a and 18b). Consequently, the representative compound 18e together with compound 18b. Marimastat and Trocade were evaluated in the rat adjuvant-induced arthritis model, a model of chronic cartilage destruction. It is concluded that the newly synthesized highly water-soluble compound 18e showed significant activity in suppressing hindpaw swelling and the bone destruction with a minimal administration period (days 3-7). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00109-8
• 作为产物：
  描述：

  D-亮氨酸 在 potassium bromide 、 sodium nitrite 作用下， 以 硫酸 为溶剂， 反应 1.0h， 生成 (R)-2-bromo-4-methylpentanoic acid
  参考文献：
  名称：

  使用含血红素的新型聚合物负载试剂进行烷基卤的亲核取代反应

  摘要：

  通过悬浮共聚反应合成了一种由氯化血红素、二乙烯基苯和2-甲基-5-乙烯基吡啶组成的新型高分子试剂。伯、仲和叔烷基卤与氯化血红素共聚物与氰化物、叠氮化物和硫氰酸根离子的取代反应得到了令人满意的产率。根据立体化学研究，该反应机理被揭示为 SNi 型。氯化血红素共聚物不仅是具有功能性的聚合物负载试剂，而且还用于将产物与反应混合物分离。

  DOI：

  10.1246/bcsj.62.2562

文献信息

• Matrix metalloprotease inhibitors
  申请人：Syntex (U.S.A.), Inc.

  公开号：US06013792A1

  公开（公告）日：2000-01-11

  Compounds of formula (I): ##STR1## as single stereoisomers or mixtures thereof and their pharmaceutically acceptable salts inhibit matrix metalloproteases, such as interstitial collagenases, and are useful in the treatment of mammals having disease states alleviated by the inhibition of such matrix metalloproteases, for example arthritic diseases or bone resorption disease, such as osteoporosis.

  公式（I）的化合物：##STR1##，作为单一立体异构体或其混合物及其药学上可接受的盐，抑制基质金属蛋白酶，如间质胶原酶，并且在治疗通过抑制这种基质金属蛋白酶而缓解的哺乳动物疾病状态中有用，例如关节炎性疾病或骨吸收疾病，如骨质疏松症。
• Mercaptosulfide metalloproteinase inhibitors
  申请人：Florida State University

  公开号：US05455262A1

  公开（公告）日：1995-10-03

  Novel mercaptosulfide matrix metalloproteinase inhibitors of the Formula I, ##STR1## wherein: n is 0 or 1; R.sup.1 is selected from the group consisting of hydrogen, lower alkyl, amino lower alkyl, carbamoyl lower alkyl, PhtN(lower alkyl), TsNH(lower alkyl); and R.sup.2 is selected from the group consisting of hydrogen, lower alkyl, amino lower alkyl, carbamoyl lower alkyl, PhtN(lower alkyl), TsNH (lower alkyl); or R.sup.1 and R.sup.2 together are --CH.sub.2 --CH.sub.2 --CH.sub.2 --; R.sup.3 is selected from the group consisting of hydrogen, lower alkyl, aralkyl and heteroaralkyl; and R.sup.4 is selected from the group consisting of hydrogen, lower alkyl, amino lower-alkyl, guanyl lower-alkyl, imidazoylalkyl, aralkyl and 2-indolylmethyl; and R.sup.5 is selected from the group consisting of lower alkyl, aralkyl and --CH(R.sup.6)--C(O)NH.sub.2, wherein R.sup.6 is selected from the group consisting of hydrogen, lower-alkyl, amino lower-alkyl, guanyl lower-alkyl, imidazoylalkyl, hydroxymethyl, 1-hydroxyethyl, mercapto lower-alkyl, and methylthio lower-alkyl; or a pharmaceutically acceptable ester, ether or salt thereof, useful for treating diseases and disease conditions associated with matrix metalloproteinase modulation.

  新型巯基硫化物基质金属蛋白酶抑制剂的化学式I，其中：n为0或1；R.sup.1选自氢、较低烷基、氨基较低烷基、氨基甲酰较低烷基、PhtN(较低烷基)、TsNH(较低烷基)的群；R.sup.2选自氢、较低烷基、氨基较低烷基、氨基甲酰较低烷基、PhtN(较低烷基)、TsNH(较低烷基)的群；或R.sup.1和R.sup.2一起为--CH.sub.2--CH.sub.2--CH.sub.2--; R.sup.3选自氢、较低烷基、芳基烷基和杂芳基烷基的群；R.sup.4选自氢、较低烷基、氨基较低烷基、胍基较低烷基、咪唑基烷基、芳基烷基和2-吲哚甲基的群；R.sup.5选自较低烷基、芳基烷基和--CH(R.sup.6)--C(O)NH.sub.2的群，其中R.sup.6选自氢、较低烷基、氨基较低烷基、胍基较低烷基、咪唑基烷基、羟甲基、1-羟乙基、巯基较低烷基和甲硫基较低烷基的群；或其药学上可接受的酯、醚或盐，用于治疗与基质金属蛋白酶调节相关的疾病和疾病症状。
• Benzoxazinone-containing 3,5-dimethylisoxazole derivatives as BET bromodomain inhibitors for treatment of castration-resistant prostate cancer
  作者：Xiaoqian Xue、Yan Zhang、Chao Wang、Maofeng Zhang、Qiuping Xiang、Junjian Wang、Anhui Wang、Chenchang Li、Cheng Zhang、Lingjiao Zou、Rui Wang、Shuang Wu、Yongzhi Lu、Hongwu Chen、Ke Ding、Guohui Li、Yong Xu

  DOI：10.1016/j.ejmech.2018.04.034

  日期：2018.5

  The bromodomain and extra-terminal proteins (BET) have emerged as promising therapeutic targets for the treatment of castration-resistant prostate cancer (CRPC). We report the design, synthesis and evaluation of a new series of benzoxazinone-containing 3,5-dimethylisoxazole derivatives as selective BET inhibitors. One of the new compounds, (R)-12 (Y02234), binds to BRD4(1) with a Kd value of 110 nM

  溴结构域和末端外蛋白（BET）已成为治疗去势抵抗性前列腺癌（CRPC）的有希望的治疗靶标。我们报告设计，合成和评估的一系列新的含苯并恶嗪酮的3,5-二甲基异恶唑衍生物作为选择性BET抑制剂。一种新化合物（R）-12（Y02234）以Kd值为110 nM结合BRD4（1），并以100 nM的IC50值阻断溴结构域和乙酰赖氨酸的相互作用。它也对非BET溴结构域蛋白表现出BET选择性，并在诸如22Rv1和C4-2B的前列腺癌细胞系中显示出合理的抗增殖和集落形成抑制作用。BRD4抑制剂（R）-12还可以在前列腺癌细胞的mRNA水平上显着抑制ERG，Myc和AR目标基因PSA的表达。（R）-12处理可在22Rv1衍生的异种移植模型中显着抑制前列腺癌的肿瘤生长（TGI = 70％）。这些数据表明化合物（R）-12是用于开发用于治疗CRPC的新型疗法的有前途的先导化合物。
• Dual-acting benzoimidazole antihypertensive agents
  申请人：Allegretti Paul

  公开号：US20080318951A1

  公开（公告）日：2008-12-25

  The invention is directed to compounds having the formula: wherein: Ar, r, n, X, R 2-3 and R 5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. These compounds have AT 1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

  这项发明涉及具有以下结构的化合物： 其中：Ar、r、n、X、R 2-3 和R 5-7 如规范中所定义，并且其药学上可接受的盐。这些化合物具有AT 1 受体拮抗活性和神经肽酶抑制活性。该发明还涉及包含这些化合物的药物组合物；使用这些化合物的方法；以及制备这些化合物的过程和中间体。
• Asymmetric Synthesis of 2-chloro- and 2-bromo-alkanoic acids by halogenation of α-D-glucofuranose-derived silyl ketene acetals
  作者：P Angibaud、J.L Chaumette、J.R Desmurs、L Duhamel、G Plé、J.Y Valnot、P Duhamel

  DOI：10.1016/0957-4166(95)00251-j

  日期：1995.8

  2-chloro-alkanoic acids 6 and 7 have been obtained the diastereoselective halogenation of chiral silyl ketene acetals 3a-f, and subsequent saponification of the resulting crude esters. Examples characterized by e.e. values up to 95% are reported. The diastereoface selectivity is independent of the silyl ketene acetal configuration.

  光学活性的（S）-2-溴-和2-氯-链烷酸6和7已经获得了手性甲硅烷基烯酮缩醛3a-f的非对映选择性卤化，随后将所得的粗酯皂化。报告了以ee值高达95％为特征的示例。非对映体的选择性与甲硅烷基烯酮缩醛构型无关。