(S)-2-(四氢呋喃-3-基)乙酸 | 146255-26-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧唑烯
• 中文名称: (S)-2-(四氢呋喃-3-基)乙酸
• 英文名称: (2(S)-tetrahydrofuranyl)acetic acid
• 英文别名: (S)-2-(Tetrahydrofuran-3-YL)acetic acid；2-[(3S)-oxolan-3-yl]acetic acid
• CAS: 146255-26-7
• 化学式: C₆H₁₀O₃
• 分子量: 130.144
• InChiKey: JSWKBJIKVSXWDJ-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 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：

  (S)-2-(四氢呋喃-3-基)乙酸 在 N-甲基吗啉 、 lithium hydroxide 、 正丁基锂 、 2,4,6-三异丙基苯磺酰叠氮化物 、 双(三甲基硅烷基)氨基钾 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.86h， 生成 (3S,4aS,8aS)-2-[(2R,3S)-3-((S)-2-Azido-2-(S)-tetrahydro-furan-3-yl-acetylamino)-2-hydroxy-4-phenyl-butyl]-decahydro-isoquinoline-3-carboxylic acid tert-butylamide
  参考文献：
  名称：

  Potent HIV protease inhibitors: the development of tetrahydrofuranylglycines as novel P2-ligands and pyrazine amides as P3-ligands

  摘要：

  A series of protease inhibitors bearing constrained unnatural amino acids at the P2-position and novel heterocycles at the P3-position of compound 1 (Ro 31-8959) were synthesized, and their in vitro enzyme inhibitory and antiviral activities were evaluated. Replacement of P2-asparagine of compound 1 with (2S,3'R)-tetrahydrofuranylglycine resulted in improvement in enzyme inhibitory as well as antiviral potencies (compound 23). Interestingly, incorporation of (2S,3'S)-tetrahydrofuranylglycine at the P2-position proved to be less effective. The resulting compound 24 was 100-fold less potent than the 2S,3R-isomer (compound 23). This stereochemical preference indicated a hydrogen-bonding interaction between the tetrahydrofuranyl oxygen and the residues of the S2-region of the enzyme active site. Furthermore, replacement of P3-quinolinoyl ligand of 1 with various novel heterocycles resulted in potent inhibitors of HIV proteases. Of particular interest, compound 2 with (2S,3'R)-tetrahydrofuranylglycine at P2 and pyrazine derivative at P3 is one of the most potent inhibitors of HIV-1 (IC50 value 0.07 nM) and HIV-2 (IC50 value 0.18 nM) proteases. Another important result in this series is the identification of compound 27 in which the P2-P3-amide carbonyl has been removed. The resulting compound 27 has exhibited improvement in antiviral potency while retaining the enzyme inhibitory potency similar to compound 1.

  DOI：

  10.1021/jm00068a006
• 作为产物：
  描述：

  diethyl (3(S)-tetrahydrofuranyl)malonate 在 copper(I) oxide 、 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 反应 84.0h， 生成 (S)-2-(四氢呋喃-3-基)乙酸
  参考文献：
  名称：

  Identification of Highly Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors against Lopinavir and Darunavir Resistant Viruses from Allophenylnorstatine-Based Peptidomimetics with P2 Tetrahydrofuranylglycine

  摘要：

  The emergence of drug-resistant HIV from a widespread antiviral chemotherapy targeting HIV protease in the past decades is unavoidable and provides a challenge to develop alternative inhibitors. We synthesized a series of allophenylnorstatine-based peptidomimetics with various P-3, P-2, and P-2' moieties. The derivatives with P-2 tetrahydrofur-anylglycine (Thfg) were found to be potent against wild type HIV-1 protease and the virus, leading to a highly potent compound 21f (KNI-1657) against lopinavir/ritonavir- or darunavir-resistant strains. Co-crystal structures of 21f and the wild-type protease revealed numerous key hydrogen bonding interactions with Thfg. These results suggest that the strategy to design allophenylnorstatine-based peptidomimetics combined with Thfg residue would be promising for generating candidates to overcome multidrug resistance.

  DOI：

  10.1021/acs.jmedchem.7b01709

文献信息

• Compounds Which Selectively Modulate The CB2 Receptor
  申请人：BARTOLOZZI Alessandra

  公开号：US20100076029A1

  公开（公告）日：2010-03-25

  Compounds of formula (I) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.

  公式（I）的化合物已被披露。根据本发明的化合物与CB2受体结合，并且是CB2受体的激动剂、拮抗剂或反向激动剂，可用于治疗炎症。那些是激动剂的化合物还可用于治疗疼痛。
• COMPOUNDS FOR THE TREATMENT OF CNS DISORDERS
  申请人：Fuchs Klaus

  公开号：US20120115863A1

  公开（公告）日：2012-05-10

  The invention relates to novel cycloalkyl- or cycloalkenyl-substituted pyrazolopyrimidinones of formula (I), wherein Ā is selected from the group A 1 consisting of a C 3 -C 8 -cycloalkyl group or a C 4 -C 8 -cycloalkenyl group, whereby the members of C 3 -C 8 -cycloalkyl group being selected from the group of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl and cyclooctanyl; and the members of the C 4 -C 8 -cycloalkenyl group, being selected from cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclopentadienyl, cyclohexadienyl, cycloheptadienyl, cyclooctadienyl, cycloheptatrienyl, cyclooctathenyl, cyclooctatetraenyl. The new compounds shall be used for the manufacture of medicaments, in particular medicaments for improving perception, concentration, learning and/or memory in patients in need thereof. Chemically, the compounds are characterised as pyrazolopyrimidinones with a cycloalkyl-moiety directly bound to the 1 position of the pyrazolopyrimidinone and a second substituent in the 6 position which is bound via an optionally substituted methylene-bridge. Further aspects of the present invention refer to a process for the manufacture of the compounds and their use for producing medicaments.

  该发明涉及具有以下结构的新型环烷基或环烯基取代的吡唑吡咪啉酮化合物（I），其中Ā选自A1组中的C3-C8环烷基或C4-C8环烯基，其中C3-C8环烷基组成员选自环丙基、环丁基、环戊基、环己基、环庚基和环辛基；而C4-C8环烯基组成员选自环丁烯基、环戊烯基、环己烯基、环庚烯基、环辛烯基、环戊二烯基、环己二烯基、环庚二烯基、环辛二烯基、环庚三烯基、环辛烷基、环辛四烯基。这些新化合物可用于制造药物，特别是用于改善患者感知、注意力、学习和/或记忆的药物。从化学上讲，这些化合物被描述为在吡唑吡咪啉酮的1位上直接连接有环烷基基团，并且在6位上通过一个可选取代的亚甲基桥连接有第二取代基。该发明的进一步方面涉及一种制造这些化合物的方法以及它们用于生产药物的用途。
• PURINE DERIVATIVES AS IMMUNOMODULATORS
  申请人：Lazarides Linos

  公开号：US20100120799A1

  公开（公告）日：2010-05-13

  Compounds of formula (I): wherein R 1 is C 1-8 alkylamino, C 1-8 alkoxy, C 3-7 cycloalkylC 1-6 alkylamino, C 3-7 cycloalkylC 1-6 alkoxy, C 1-3 alkoxyC 2-3 alkoxy, or Het b -C 1-3 alkoxy; Het b is a 5- or 6-membered saturated aliphatic heterocycle containing one oxygen atom; R 2 is —(CH 2 ) n -Het; n is an integer having a value of 1 to 4; Het is a 5- or 6-membered saturated aliphatic heterocycle containing one oxygen heteroatom, which heterocycle may be substituted by one or two C 1-4 alkyl groups, and salts and solvates thereof, are inducers of human interferon and may be useful in the treatment of various disorders in particular infectious diseases, cancer, and allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, and as vaccine adjuvants.

  化合物的式子(I)：其中R1是C1-8烷基氨基，C1-8烷氧基，C3-7环烷基C1-6烷基氨基，C3-7环烷基C1-6烷氧基，C1-3烷氧基C2-3烷氧基或Hetb-C1-3烷氧基；Hetb是含有一个氧原子的5-或6-成员饱和脂肪族杂环；R2是—(CH2)n-Het；n是一个值为1到4的整数；Het是含有一个氧杂原子的5-或6-成员饱和脂肪族杂环，该杂环可能被一个或两个C1-4烷基基团取代，以及其盐和溶剂化物，是人类干扰素的诱导剂，可用于治疗各种疾病，特别是感染性疾病、癌症、过敏性疾病和其他炎症状况，例如过敏性鼻炎和哮喘，并作为疫苗佐剂。
• COMPOUNDS
  申请人：Lazarides Linos

  公开号：US20110269781A1

  公开（公告）日：2011-11-03

  The present invention includes novel compounds useful in the treatment of various disorders in particular infectious diseases, cancer, and allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, and as vaccine adjuvants.

  本发明涵盖了新型化合物，可用于治疗各种疾病，特别是感染性疾病、癌症、过敏性疾病和其他炎症病症，例如过敏性鼻炎和哮喘，并可用作疫苗佐剂。
• Therapeutic Uses of Compounds Which Selectively Modulate The CB2 Receptor
  申请人：BARTOLOZZI Alessandra

  公开号：US20110312932A1

  公开（公告）日：2011-12-22

  Compounds of formula (I) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.

  本发明揭示了式(I)的化合物。该发明的化合物与CB2受体结合并且是激动剂、拮抗剂或反向激动剂，可用于治疗炎症。那些是激动剂的化合物还可用于治疗疼痛。