顺式-4-苯基-L-脯氨酸 | 103290-40-0

• 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
• 中文名称: 顺式-4-苯基-L-脯氨酸
• 英文名称: cis-4-phenyl-L-proline
• 英文别名: (2S,4R)-4-phenylpyrrolidin-1-ium-2-carboxylate
• CAS: 103290-40-0
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: JHHOFXBPLJDHOR-UWVGGRQHSA-N

物化性质

• 密度：
  1.186

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  顺式-4-苯基-L-脯氨酸 在 platinum(IV) oxide 三甲基溴硅烷 、 氢气 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 48.0h， 生成 (2S,4R)-4-Cyclohexyl-1-{2-[hydroxy-(4-phenyl-butyl)-phosphinoyl]-acetyl}-pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines

  摘要：

  Analogues of captopril, enalaprilat, and the phosphinic acid [hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.

  DOI：

  10.1021/jm00401a014
• 作为产物：
  描述：

  (2S,4R)-N-叔丁氧羰基-4-苯基吡咯烷-2-甲酸 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 顺式-4-苯基-L-脯氨酸
  参考文献：
  名称：

  Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions

  摘要：

  本公开提供了一种新型的大环肽，可以抑制PD-1/PD-L1和PD-L1/CD80蛋白质相互作用，因此对改善包括癌症和传染病在内的各种疾病有用。

  公开号：

  US09308236B2

文献信息

• Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：US20160095858A1

  公开（公告）日：2016-04-07

  The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R 1 , R 2 , R 3 , W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

  本发明涉及一种具有以下化学式I的化合物： 或其药用可接受的盐，其中R 1 ，R 2 ，R 3 ，W，X，Y，Z，n，o，p和q在此处定义，用于治疗CFTR介导的疾病，如囊性纤维化。本发明还涉及药物组合物、治疗方法和相关工具包。
• [EN] HETEROCYCLIC INHIBITORS OF BETA - SECRETASE FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE LA BÊTA-SECRÉTASE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2012071458A1

  公开（公告）日：2012-05-31

  The invention provides novel tricyclic compounds of Formula I' that inhibit β-secretase cleavage of APP and are useful as therapeutic agents for treating neurodegenerative diseases.

  本发明提供了一种抑制β-分泌酶裂解APP的新颖三环化合物，式I'，可用作治疗神经退行性疾病的治疗剂。
• CONFORMATIONALLY CONSTRAINED, FULLY SYNTHETIC MACROCYCLIC COMPOUNDS
  申请人：POLYPHOR AG

  公开号：US20150051183A1

  公开（公告）日：2015-02-19

  The conformationally restricted, spatially defined macrocyclic ring system of formula (I) is constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. Macrocycles described by this ring system I are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), inhibitory activity on enzymes or antimicrobial activity. In particular, these macrocycles show inhibitory activity on endothelin converting enzyme of subtype 1 (ECE-1) and/or the cysteine protease cathepsin S (CatS), and/or act as antagonists of the oxytocin (OT) receptor, thyrotropin-releasing hormone (TRH) receptor and/or leukotriene B4 (LTB4) receptor, and/or as agonists of the bombesin 3 (BB3) receptor, and/or show antimicrobial activity against at least one bacterial strain. Thus they are showing great potential as medicaments for a variety of diseases.

  公式（I）的构象受限、空间定义的大环环系统由三个不同的分子部分组成：模板A、构象调节剂B和桥C。由这种环系统I描述的大环可通过并行合成或溶液中或固相上的组合化学轻松制造。它们被设计用于与各种特定生物靶标类相互作用，例如在G蛋白偶联受体（GPCR）上的激动或拮抗活性，酶的抑制活性或抗菌活性。特别是，这些大环显示对亚型1的内皮素转化酶（ECE-1）和/或半胱氨酸蛋白酶卡特普辛S（CatS）的抑制活性，和/或作为催产素（OT）受体、促甲状腺释放激素（TRH）受体和/或白三烯B4（LTB4）受体的拮抗剂，和/或作为瘤胃素3（BB3）受体的激动剂，和/或对至少一种细菌菌株显示抗菌活性。因此，它们显示出作为各种疾病药物的巨大潜力。
• PEPTIDES AND PEPTIDOMIMETIC COMPOUNDS, THE MANUFACTURING THEREOF AS WELL AS THEIR USE FOR PREPARING A THERAPEUTICALLY AND/OR PREVENTIVELY ACTIVE PHARMACEUTICAL COMPOSITION
  申请人：PETZELBAUER Peter

  公开号：US20100081787A1

  公开（公告）日：2010-04-01

  Peptides, peptidomimetics and derivatives thereof of the general formula I: H 2 N-GHRPX 1 - β -X 4 X 5 X 6 X 7 X 8 X 9 X 10 -X 11 (I), in which X 1 -X 10 denote one of the 20 genetically coded amino acids, wherein X 8 , X 9 and X 10 may also denote a single chemical bond; X 11 denotes OR 1 in which R 1 equals hydrogen or (C 1 -C 10 ) alkyl NR 2 R 3 with R 2 and R 3 are equal or different and denote hydrogen, (C 1 -C 10 ) alkyl, or a residue —W-PEG 5-60K , in which the PEG residue is attached via a suitable spacer W to the N-atom, or a residue NH—Y-Z-PEG 5-60K , in which Y denotes a chemical bond or a genetically coded amino acids from the group S, C, K or R and Z denotes a spacer, via which a polyethylene glycol (PEG)-residue can be attached, and their physiologically acceptable salts, and β denotes an amino acid, or a peptidomimetic element, which induces a bend or turn in the peptide backbone.

  通用公式I：H2N-GHRPX1-β-X4X5X6X7X8X9X10-X11(I)中的肽、肽类似物和衍生物，其中X1-X10表示20种遗传编码的氨基酸之一，其中X8、X9和X10也可以表示单一化学键；X11表示OR1，其中R1等于氢或(C1-C10)烷基NR2R3，其中R2和R3相同或不同，表示氢、(C1-C10)烷基，或者残基—W-PEG5-60K，其中PEG残基通过适当的间隔物W连接到N-原子，或者残基NH—Y-Z-PEG5-60K，其中Y表示化学键或来自S、C、K或R组的遗传编码氨基酸，Z表示间隔物，通过该间隔物可以连接聚乙二醇（PEG）残基，并且它们的生理上可接受的盐，β表示氨基酸或诱导肽骨架中弯曲或转弯的肽类或肽类似元素。
• RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：The Johns Hopkins University

  公开号：US20210094933A1

  公开（公告）日：2021-04-01

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受免疫蛋白配体家族FK506和雷帕霉素天然产物启发的大环化合物。生成包含FK506和雷帕霉素结合结构域的Rapafucin大环化合物库，应具有作为治疗疾病新药的潜力。