4-amino-2,2-dimethylbutanoic acid hydrochloride | 153039-15-7

• 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: 4-amino-2,2-dimethylbutanoic acid hydrochloride
• 英文别名: 4-amino-2,2-dimethylbutanoic acid;hydrochloride
• CAS: 153039-15-7
• 化学式: C₆H₁₃NO₂*ClH
• 分子量: 167.636
• InChiKey: FBYVPNQCVJSPPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.27
• 重原子数：
  10
• 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：
  64.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-amino-2,2-dimethylbutanoic acid hydrochloride 在 sodium acetate 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 5.17h， 生成 4-[[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]amino]-2,2-dimethylbutanoic acid
  参考文献：
  名称：

  Biphenylsulfonamide Endothelin Receptor Antagonists. 4. Discovery of N-[[2‘-[[(4,5-Dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1‘-biphenyl]- 2-yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940), A Highly Potent and Orally Active ET_A Selective Antagonist

  摘要：

  We have previously disclosed the selective ETA receptor antagonist N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (1, BMS-193884) as a clinical development candidate. Additional SAR studies at the 2'-position of 1 led to the identification of several analogues with improved binding affinity as well as selectivity for the ETA receptor. Following the discovery that a 3-amino-isoxazole group displays significantly improved metabolic stability in comparison to its 5-regioisomer, the 3-amino-isoxazole group was combined with the optimal 2'-substituent lleading to 16a (BMS-207940). Compound 16a is an extremely potent (ETAKi = 10 pM) and selective (80000-fold for ETA vs ETB) antagonist. It is also 150-fold more potent and >6-fold more selective than 1. The bioavailability of 16a was 100% in rats and the systemic clearance and volume of distribution are higher than that of 1. In rats, intravenous 16a blocks big ET pressor responses with 30-fold greater potency than 1. After oral dosing at 3 mumol/kg, 16a displays enhanced duration relative to 1.

  DOI：

  10.1021/jm020289q
• 作为产物：
  描述：

  3,3-二甲基-2-氧代吡咯烷 在 盐酸 作用下， 以 水 为溶剂， 反应 12.0h， 生成 4-amino-2,2-dimethylbutanoic acid hydrochloride
  参考文献：
  名称：

  自动消散垫片可将独特的固态荧光团首次结合到酰基水解酶的检测探针中

  摘要：

  注意您的HPQ：通过使用自消灭环化间隔物以及与HPQ连接的酰化O，O-乙缩醛，开发了一种基于独特的固态荧光团HPQ的可检测特定肽酶的探针（请参见方案）。在我们的测定条件下，该探针检测到酶的最小半衰期仅为560 s。

  DOI：

  10.1002/chem.200902412

文献信息

• [EN] SPIRO CYCLOPENTANE COMPOUNDS USEFUL AS ANTAGONISTS OF THE H1-RECEPTOR<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2009016084A1

  公开（公告）日：2009-02-05

  This invention relates to novel spiro cyclopentane derivatives of formula (I) or a pharmaceutically acceptable salt thereof, for treating diseases and conditions of the central nervous system (CNS), in particular sleep disorders.

  该发明涉及公式（I）的新颖螺环戊烷衍生物或其药用盐，用于治疗中枢神经系统（CNS）的疾病和病症，特别是睡眠障碍。
• [EN] LIPIDS AND LIPID COMPOSITIONS FOR THE DELIVERY OF ACTIVE AGENTS<br/>[FR] LIPIDES ET COMPOSITIONS LIPIDIQUES PERMETTANT L'ADMINISTRATION DE PRINCIPES ACTIFS
  申请人：NOVARTIS AG

  公开号：WO2016037053A1

  公开（公告）日：2016-03-10

  This invention provides for a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RA, RB, R2 and R4 are defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.

  这项发明提供了一个式（I）的化合物，或者其药学上可接受的盐，其中RA、RB、R2和R4在此处定义。式（I）的化合物及其药学上可接受的盐是阳离子脂质，可用于将生物活性物质传递给细胞和组织。
• [EN] NOVEL CYCLIC CATIONIC LIPIDS AND METHODS OF USE<br/>[FR] NOUVEAUX LIPIDES CATIONIQUES CYCLIQUES ET PROCÉDÉS D'UTILISATION
  申请人：PROTIVA BIOTHERAPEUTICS INC

  公开号：WO2011141704A1

  公开（公告）日：2011-11-17

  The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid- lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

  本发明提供了用于将治疗剂传递至细胞的组合物和方法。具体包括新型阳离子脂质和核酸-脂质颗粒，能够有效地封装核酸并有效地将封装的核酸传递至体内细胞。本发明的组合物非常强效，因此能够以相对较低的剂量有效地降低特定靶蛋白的表达。此外，与先前已知的组合物和方法相比，本发明的组合物和方法毒性较低，提供更大的治疗指数。
• Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists
  申请人：——

  公开号：US20020143024A1

  公开（公告）日：2002-10-03

  Novel biphenyl sulfonamide compounds which are combined angiotensin and endothelin receptor antagonists are claimed along with methods of using such compounds in the treatment of conditions such as hypertension and other diseases, as well as pharmaceutical compositions containing such compounds.

  声称结合了血管紧张素和内皮素受体拮抗剂的新型联苯磺酰胺化合物，以及使用这种化合物治疗高血压和其他疾病的方法，以及含有这种化合物的药物组合物。
• Discovery of <i>N</i>-Isoxazolyl Biphenylsulfonamides as Potent Dual Angiotensin II and Endothelin A Receptor Antagonists
  作者：Natesan Murugesan、John E. Tellew、Zhengxiang Gu、Bridgette L. Kunst、Leena Fadnis、Lyndon A. Cornelius、Rose Ann F. Baska、Yifan Yang、Sophie M. Beyer、Hossain Monshizadegan、Kenneth E. Dickinson、Balkrushna Panchal、Maria T. Valentine、Saeho Chong、Richard A. Morrison、Kenneth E. Carlson、James R. Powell、Suzanne Moreland、Joel C. Barrish、Mark C. Kowala、John E. Macor

  DOI：10.1021/jm020138n

  日期：2002.8.1

  both receptors. This strategy led to the design, synthesis, and discovery of (15) (4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-[1,1'-biphenyl]-2-sulfonamide, BMS-248360) as a potent and orally active dual antagonist of both AT(1) and ET(A) receptors. Compound 15 represents a new approach to treating hypertension

  ET（A）受体拮抗剂（2）（N-（3,4-二甲基-5-异恶唑基）-4'-（2-恶唑基）-[1,1'-联苯] -2-磺酰胺，BMS-193884 ）与大量的AT（1）受体拮抗剂（包括厄贝沙坦（3））具有相同的联苯核心。因此，假设将2的结构元素与联苯AT（1）拮抗剂（例如厄贝沙坦）的结构元素合并将产生对两种受体均具有双重活性的化合物。这种策略导致设计，合成和发现（15）（4'-[（2-butyl-4-oxo-1,3-diazaspiro [4.4] non-1-en-3-yl）methyl]- N-（3,4-二甲基-5-异恶唑基）-2'-[（3,3-二甲基-2-氧代-1-吡咯烷基）甲基]-[1,1'-联苯] -2-磺酰胺，BMS -248360）作为AT（1）和ET（A）受体的有效和口服活性双重拮抗剂。化合物15代表了一种治疗高血压的新方法。