(-)-2,3-dihydro-1-benzofuran-2-carboxylic acid | 63559-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: (-)-2,3-dihydro-1-benzofuran-2-carboxylic acid
• 英文别名: 2,3-dihydrobenzofuran-2(S)-carboxylic acid；l-2,3-dihydrobenzo-2-furoic acid；(S)-2,3-dihydro-benzofuran-2-carboxylic acid；(S)-2,3-Dihydro-benzofuran-2-carbonsaeure；(S)-2,3-dihydro-benzofuran-2-carboxylic acid；2,3-Dihydro-benzofuran-2-carbonsaeure；(2S)-2,3-dihydro-1-benzofuran-2-carboxylic acid
• CAS: 63559-46-6
• 化学式: C₉H₈O₃
• 分子量: 164.161
• InChiKey: WEVFUSSJCGAVOH-QMMMGPOBSA-N

物化性质

• 熔点：
  104-105 °C(Solv: carbon tetrachloride (56-23-5))
• 沸点：
  340.5±31.0 °C(Predicted)
• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-2,3-dihydro-1-benzofuran-2-carboxylic acid 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 硝酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 (S)-5-methanesulfonylamino-2,3-dihydro-benzofuran-2-carboxylic-acid-{2-[(S)-3-hydroxy-pyrrolidin-1-yl]-(S)-1-phenyl-ethyl}-methyl-amide
  参考文献：
  名称：

  Potent and highly selective kappa opioid receptor agonists incorporating chroman- and 2,3-dihydrobenzofuran-based constraints

  摘要：

  Two novel chemical classes of kappa opioid receptor agonists, chroman-2-carboxamide derivatives and 2,3-dihydrobenzofuran-2-carboxamide derivatives, were synthesized. These agents exhibited high and selective affinity for the kappa opioid receptor. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.094
• 作为产物：
  描述：

  苯并二氢呋喃-2-羧酸 生成 (-)-2,3-dihydro-1-benzofuran-2-carboxylic acid
  参考文献：
  名称：

  Fredga; Vazquez de Castro y Sarmiento, Arkiv foer Kemi, 1954, vol. 7, p. 387,388, 389

  摘要：

  DOI：

文献信息

• Fused bicyclic carboxamide derivatives and methods of their use
  申请人：Dolle E. Roland

  公开号：US20050054630A1

  公开（公告）日：2005-03-10

  Fused bicyclic carboxamide derivatives are disclosed. Pharmaceutical compositions containing the compounds and methods for their use are also disclosed.

  揭示了融合的双环羧酰胺衍生物。还公开了含有这些化合物的药物组合物以及它们的使用方法。
• Fluorinated lysine derivatives as dipeptidyl peptidase IV inhibitors
  申请人：Parker C. Janice

  公开号：US20050043292A1

  公开（公告）日：2005-02-24

  The invention relates to new therapeutically active and selective inhibitors of the enzyme dipeptidyl peptidase-IV (“DPP-IV”), pharmaceutical compositions comprising the compounds and the use of such compounds for treating diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes, metabolic syndrome (syndrome X or insulin resistance syndrome), hyperglycemia, impaired glucose tolerance, glucosuria, metabolic acidosis, arthritis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, inflammatory bowel syndrome and to prevent disease progression in Type 2 diabetes. The invention also relates to a method of identifying an insulin secretagogue agent for diabetes.

  该发明涉及新的具有治疗活性和选择性的酶二肽基肽酶-IV（“DPP-IV”）抑制剂，包括这些化合物的药物组合物以及利用这些化合物治疗与受DPP-IV加工的蛋白质相关的疾病，如2型糖尿病、代谢综合征（综合征X或胰岛素抵抗综合征）、高血糖、糖耐量受损、糖尿病、代谢性酸中毒、关节炎、白内障、糖尿病性神经病变、糖尿病性肾病、糖尿病性视网膜病变、糖尿病性心肌病、1型糖尿病、肥胖、由肥胖恶化的疾病、高血压、高脂血症、动脉粥样硬化、骨质疏松症、脆弱性、骨质流失、骨折、急性冠状动脉综合征、多囊卵巢综合征导致的不孕症、短肠综合征、焦虑、抑郁症、失眠、慢性疲劳、癫痫、进食障碍、慢性疼痛、酒精成瘾、与肠道蠕动有关的疾病、溃疡、肠易激综合征、炎症性肠病以及预防2型糖尿病疾病进展的方法。该发明还涉及一种用于识别糖尿病胰岛素分泌素的方法。
• Comparison of Deacylation Rates of Chymotryptic Catalysis within an Enantiomeric Pair of p-Nitrophenyl Esters.
  作者：Kazutaka TANIZAWA、Hiroyuki YAMADA、Kunihiko ITOH、Yuichi KANAOKA

  DOI：10.1248/cpb.39.2748

  日期：——

  p-Nitrophenyl esters carrying a chiral acyl group were synthesized. These compounds were shown to meet the requirements of chymotrypsin for the specific binding and the acylation. Therefore, the behavior of p-nitrophenyl esters with chymotrypsin is considered to be virtually identical to that of p-amidinophenyl esters with trypsin which were proposed as "inverse substrates" for the enzyme. These esters, derived from each pair of enantiomers, have been successfully used for the analysis of enantiomeric preference of chymotrypsin at the deacylation stage. The chiral requirement of the enzyme active site for the catalytic efficiency was discussed.

  合成了带有手性酰基的对硝基苯基酯。这些化合物被证明符合胰蛋白酶在特定结合和酰化方面的要求。因此，认为对硝基苯基酯与胰蛋白酶的作用几乎与对氨基苯基酯与胰酶的作用相同，后者被提议作为该酶的“逆底物”。这些酯源自每对对映体，已成功用于分析胰蛋白酶在去酰化阶段的对映体偏好。讨论了酶活性位点对催化效率的手性需求。
• Lipase-mediated kinetic resolution of rigid clofibrate analogues with lipid-modifying activity
  作者：Savina Ferorelli、Carlo Franchini、Fulvio Loiodice、Maria Grazia Perrone、Antonio Scilimati、Maria Stefania Sinicropi、Paolo Tortorella

  DOI：10.1016/s0957-4166(01)00119-7

  日期：2001.4

  workable reaction rates. Enantiomerically pure (R)- and (S)-5-chloro-2,3-dihydro-1-benzofuran-2-carboxylic acids were obtained by fractional crystallisation of the diastereomeric salts of the corresponding racemic acid with (+)- and (−)-amphetamine from ethanol; the absolute configuration of the products were established by chemical correlation.

  （±）-5-氯-2,3-二氢-1-苯并呋喃-2-羧酸，（±）甲酯的脂肪酶催化的动力学拆分-6-氯-2,3-二氢-4- ħ -氯贝贝特的刚性类似物1-苯并吡喃-2-羧酸和（±）-6-氯-2,3-二氢-4 H -1-苯并吡喃-3-羧酸具有中等至中等对映选择性（E = 1.0–4.8），对映体过量高达86％，反应速率可行。对映体纯的（R）-和（S通过将相应的外消旋酸的非对映异构盐与（+）-和（-）-苯异丙胺从乙醇中分步结晶得到）-5-氯-2,3-二氢-1-苯并呋喃-2-羧酸。产品的绝对构型是通过化学相关性确定的。
• Heteroaryl substituted 2-pyridinyl and 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one derivatives
  申请人：Lochead Alistair

  公开号：US20050222172A1

  公开（公告）日：2005-10-06

  The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: (1) X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring optionally substituted; R2 represents a heterocyclic bicyclic rings, having 1-4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom and having 5-9 carbon atoms, of formula (II) R3 represents a hydrogen atom, a C 1-6 alkyl group, a hydroxy group, a C 1-4 alkoxy group or a halogen atom; R4 represents a hydrogen atom, a C 1-6 alkyl group, a C 1-4 alkoxy group or a halogen atom. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β or GSK3β and cdk5/p25, such as Alzheimer disease.

  本发明涉及一种由式（I）表示的嘧啶酮衍生物或其盐，其中：（1）X代表两个氢原子、一个硫原子、一个氧原子或一个C1-2烷基和一个氢原子；Y代表一种键合、一个乙烯基、一个乙炔基或一个甲基烷基，可选地取代；R1代表一个2、3或4-吡啶环或一个2、4或5-嘧啶环，可选地取代；R2代表一种杂环双环环，具有1-4个从氧原子、硫原子和氮原子中选择的杂原子，并具有5-9个碳原子，其式为（II）R3代表氢原子、C1-6烷基、羟基、C1-4烷氧基或卤素原子；R4代表氢原子、C1-6烷基、C1-4烷氧基或卤素原子。本发明还涉及一种药物，其包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β或GSK3β和cdk5/p25的异常活性引起的神经退行性疾病，例如阿尔茨海默病。