D-3-(1-naphthyl)alanine methylester | 223771-37-7

• 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: D-3-(1-naphthyl)alanine methylester
• 英文别名: methyl (2R)-2-amino-3-(naphthalen-1-yl)propanoate；methyl (2R)-2-amino-3-naphthalen-1-ylpropanoate
• CAS: 223771-37-7
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: OQJPYIXRWGSJOL-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  D-3-(1-naphthyl)alanine methylester 在 lithium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (2R)-2-[(2-bromobenzoyl)amino]-3-naphthalen-1-ylpropanoic acid
  参考文献：
  名称：

  N-Benzoyl amino acids as LFA-1/ICAM inhibitors 1: amino acid structure–activity relationship

  摘要：

  The association of ICAM-1 with LFA-1 plays a critical role in several autoimmune diseases. N-2-Bromobenzoyl L-tryptophan, compound 1, was identified as an inhibitor to the formation of the LFA-1/ICAM complex. The SAR of the amino acid indicates that the carboxylic acid is required for inhibition and that L-histidine is the most favored amino acid. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00084-2
• 作为产物：
  描述：

  D-3-(1-萘基)-丙氨酸盐酸盐 在 氯化亚砜 作用下， 以 甲醇 为溶剂， 反应 21.0h， 生成 D-3-(1-naphthyl)alanine methylester
  参考文献：
  名称：

  CXCR4-ANTAGONISTIC DRUGS COMPRISING NITROGEN-CONTAINING COMPOUND

  摘要：

  为基于CXCR4拮抗作用提供对CXCR4具有拮抗作用的新型含氮化合物和治疗风湿病、癌症转移等疾病的药物。以下是一般式代表的含氮化合物和以这些化合物为活性成分的CXCR4拮抗剂。上述化合物以以下一般式（I）代表的含氮化合物为代表，其中A1和A2分别代表鸟氨基基团或由以下一般式（ia）代表的基团（其中A3代表具有1个或2个杂原子的单环或多环杂环芳香环基团；B1代表单键或烷基基团；R1代表氢或烷基基团；W代表具有2至3个碳原子的烷基基团、具有5至10个碳原子的环烷基团、具有6至10个碳原子的芳香环或具有5至10个碳原子的杂环芳香环；y为-(C=O)-；x为-C(=O)-NH-；n1为1或2的整数；n2为2或3的整数；D从各种取代基中选择）。

  公开号：

  EP1389460A1

文献信息

• NITROGENOUS COMPOUNDS AND ANTIVIRAL DRUGS CONTAINING THE SAME
  申请人：Kureha Chemical Industry Co., Ltd.

  公开号：EP1273571A1

  公开（公告）日：2003-01-08

  The present invention provides novel compounds having antiviral activities and antiviral drugs containing the compounds as the active ingredient. The compounds are shown by the following general formula (1), wherein typically A1 and A2 are each guanidine or a group of the general fomula (ia) ; A3 is a mono- or poly-cyclic heteroaromatic ring contining 1 or 2 heteroatoms ; B1 is a single bond or alkylene group; R1 is hydrogen or alkyl group; W is an alkylene having 2-3 carbons, a cycloalkylene having 5-10 carbons, aromatic ring having 6-10 carbons, or a heteroaromatic ring having 5-10 carbons; y is C(=O)-; x is -C(=O)-NH-; n1 is an integer of 1-2; n2 is an integer of 2-3; D is a substituent selected from among various groups.

  本发明提供了具有抗病毒活性的新化合物以及含有这些化合物作为活性成分的抗病毒药物。这些化合物由以下一般式（1）所示，其中通常A1和A2分别是胍或一般式（ia）的基团；A3是含有1个或2个杂原子的单环或多环杂芳环；B1是单键或烷基基团；R1是氢或烷基基团；W是具有2-3个碳的烷基、具有5-10个碳的环烷基、具有6-10个碳的芳香环或具有5-10个碳的杂芳环；y是C(=O)-；x是-C(=O)-NH-；n1是1-2的整数；n2是2-3的整数；D是从各种基团中选择的取代基。
• An increase in side-group hydrophobicity largely improves the potency of ritonavir-like inhibitors of CYP3A4
  作者：Eric R. Samuels、Irina F. Sevrioukova

  DOI：10.1016/j.bmc.2020.115349

  日期：2020.3

  naphthalene in different stereo configuration showed that (i) analogues with the R2-naphthalene tend to bind tighter and inhibit CYP3A4 more potently than the R2-phenyl/indole containing counterparts; (ii) stereochemistry becomes a more important contributing factor, as the bulky side-groups limit the ability to optimize protein-ligand interactions; (iii) the relationship between the R1/R2 configuration and

  确定有效抑制药物代谢性细胞色素P450 3A4（CYP3A4）所需的结构决定簇可以帮助开发更安全的药物和更有效的药物增强剂。我们利用合理的抑制剂设计来解释利托那韦类似物的结构活性关系，利托那韦是一种作为药物增强剂销售的高效CYP3A4抑制剂。分析具有不同立体结构的R1侧基为苯基或萘，R2为吲哚或萘的化合物显示：（i）与R2-萘类似的化合物比R2-苯基/吲哚具有更紧密的结合力和更强的CYP3A4抑制力包含同行 （ii）立体化学成为一个更重要的贡献因素，因为庞大的侧基限制了优化蛋白质-配体相互作用的能力；（iii）R1 / R2构型与优先结合CYP3A4的关系很复杂，并且取决于侧基的功能性/相互作用和主链间距；（iv）三种抑制剂5a-b和7d优于利托那韦（IC50分别为0.055-0.085μM和0.130μM）。
• Nitrogenous compounds and antiviral drugs containing the same
  申请人：——

  公开号：US20040092556A1

  公开（公告）日：2004-05-13

  The present invention provides novel compounds having antiviral activities and antiviral drugs containing the compounds as the active ingredient. The compounds are shown by the following general formula (1), wherein typically A 1 and A 2 are each guanidine or a group of the general fomula (ia); A 3 is a mono- or poly-cyclic heteroaromatic ring contining 1 or 2 heteroatoms; B 1 is a single bond or alkylene group; R 1 is hydrogen or alkyl group; W is an alkylene having 2-3 carbons, a cycloalkylene having 5-10 carbons, aromatic ring having 6-10 carbons, or a heteroaromatic ring having 5-10 carbons; y is C(═O)—; x is —C(═O)—NH—; n 1 is an integer of 1-2; n 2 is an integer of 2-3; D is a substituent selected from among various groups. 1

  本发明提供了具有抗病毒活性的新化合物和包含该化合物作为活性成分的抗病毒药物。该化合物由以下通式（1）表示，其中通常A1和A2分别是鸟氨酸或通式（ia）的基团；A3是含有1或2个杂原子的单环或多环杂芳基环；B1是单键或烷基链；R1是氢或烷基基团；W是具有2-3个碳的烷基，具有5-10个碳的环烷基，具有6-10个碳的芳环基或具有5-10个碳的杂芳基环；y是C（═O）-；x是-C（═O）-NH-；n1是1-2的整数；n2是2-3的整数；D是从各种基团中选择的取代基。
• Reduced size LHRH analogs
  申请人：ABBOTT LABORATORIES

  公开号：EP0328089A2

  公开（公告）日：1989-08-16

  The present invention relates to novel LHRH analogs. The LHRH analogs include "pseudo" hexapeptide, heptapeptide, octapeptide and nonapeptide analogs of LHRH, wherein all or some of the amino acids 1, 2 and 3 have been eliminated and the remaining (2-9), (2-10), (3-9), (3-10), (4-9) or (4-10) peptide is linked to various carboxylic acids which take the place of amino acids 1, 2 or 3 in LHRH.

  本发明涉及新型 LHRH 类似物。LHRH 类似物包括 LHRH 的 "伪 "六肽、七肽、八肽和非肽类似物，其中全部或部分氨基酸 1、2 和 3 已被去除，剩余的(2-9)、(2-10)、(3-9)、(3-10)、(4-9)或(4-10)肽与各种羧酸相连，取代了 LHRH 中的氨基酸 1、2 或 3。
• The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 1
  作者：Xiaojun Han、Rita L. Civiello、Charles M. Conway、Deborah A. Cook、Carl D. Davis、Robert Macci、Sokhom S. Pin、Shelly X. Ren、Richard Schartman、Laura J. Signor、George Thalody、Kimberly A. Widmann、Cen Xu、Prasad V. Chaturvedula、John E. Macor、Gene M. Dubowchik

  DOI：10.1016/j.bmcl.2012.05.074

  日期：2012.7

  We have systematically studied the effects of varying the central unnatural amino acid moiety on CGRP receptor antagonist potency and CYP inhibition in a series of ureidoamides. In this Letter, we report the discovery of compound 23, a potent CGRP receptor antagonist with only weak CYP3A4 inhibition. Unlike the triptans, compound 23 did not cause active constriction of ex vivo human cerebral arteries. At doses of 0.3-1 mg/kg (sc), 23 showed robust inhibition of CGRP-induced increases in marmoset facial blood flow, a validated migraine model. Ureidoamide 23 derives from a novel amino acid, 1H-indazol-5-yl substituted alanine as a tyrosine surrogate. (C) 2012 Elsevier Ltd. All rights reserved.