(S)-1,2,3,4-四氢-3-异喹啉羧酸叔丁酯盐酸盐 | 77497-74-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 羧酸酯及其衍生物
• 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: (S)-1,2,3,4-四氢-3-异喹啉羧酸叔丁酯盐酸盐
• 中文别名: (S)-1,2,3,4-四氢-3-异喹啉羧酸叔丁酯；[S]-1,2,3,4-四氢异喹啉-3-羧酸叔丁酯；[S]-1,2,3,4-四氢异喹啉-3-羧酸叔丁酯盐酸盐
• 英文名称: (S)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, 1,1-dimethylethyl ester
• 英文别名: tert-butyl (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate；tert-butyl (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate；H-Tic-OtBu；(3S)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid tert-butyl ester；tert.-butyl (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate；(S)-Tert-butyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate
• CAS: 77497-74-6
• 化学式: C₁₄H₁₉NO₂
• mdl: MFCD04114841
• 分子量: 233.31
• InChiKey: KRSUDBIZXKOKGA-LBPRGKRZSA-N

物化性质

• 沸点：
  331.6±30.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933499090
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  (S)-1,2,3,4-四氢-3-异喹啉羧酸叔丁酯盐酸盐 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 喹那普利
  参考文献：
  名称：

  新型血管紧张素转化酶抑制剂奎纳普利及其相关化合物的合成。非巯基和巯基类型的结构活性关系存在差异。

  摘要：

  据报道奎纳普利（CI-906，22），其活性二酸（CI-928，33）和其二甲氧基类似物（CI-925，25）的合成和血管紧张素转化酶（ACE）抑制活性。这些四氢-3-异喹啉羧酸衍生物具有与依那普利相当的体外效能和体内功效。具有相同结构变化的巯基类似物也非常有效。相反，四氢-1-异喹啉羧酸和同源异吲哚啉-1-羧酸类似物在两种类型的效力上显示出惊人的差异，巯基类似物基本上是无活性的，而非巯基类似物与脯氨酸原型是等效的。这是第一个证据表明小分子ACE抑制剂的两个主要结构类别可能存在其他结合模式。

  DOI：

  10.1021/jm00160a026
• 作为产物：
  描述：

  3,4-二氢一异喹啉-2,3-二甲酸-2-苄酯 在 palladium on activated charcoal 硫酸 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 362.0h， 生成 (S)-1,2,3,4-四氢-3-异喹啉羧酸叔丁酯盐酸盐
  参考文献：
  名称：

  Evolution of the Dmt-Tic Pharmacophore:  N-Terminal Methylated Derivatives with Extraordinary δ Opioid Antagonist Activity

  摘要：

  The delta opioid antagonist H-Dmt-Tic-OH (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) exhibits extraordinary delta receptor binding characteristics [K-i(delta) = 0.022 nM; K-i(u)/K-i(delta) = 150 000] and delta antagonism (pA(2) = 8.2; K-e = 5.7 nM). A change in chirality of Dmt at C alpha (1, 2, 6, 8, 10, 13) curtailed delta receptor parameters, while replacement of its alpha-amino function by a methyl group (3) led to inactivity; Tyr-Tic analogues 4 and 11 weakly interacted with delta receptors. N-Alkylation of H-Dmt-Tic-OH and H-Dmt-Tic-Ala-OH with methyl groups produced potent delta-opioid ligands with high delta receptor binding capabilities and enhanced delta antagonism: (i) N-Me-Dmt-Tic-OH 5 had high delta opioid binding (K-i(delta) = 0.2 nM), elevated delta antagonism on mouse vas deferens (MVD) (pA(2) = 8.5; K-e = 2.8 nM), and nondetectable mu activity with guinea pig ileum (GPI). (ii) N,N-Me-2-Dmt-Tic-OH (12) was equally efficacious in delta receptor binding (K-i(delta) = 0.12 nM; K-i(mu)/K-i(delta) = 20 000), but delta antagonism rose considerably (pA(2) = 9.4; K-e = 0.28 nM) with weak mu antagonism (pA(2) = 5.8; K-e = 1.58 mu M; GPI/MVD = 1:5640). N-Me-(9) and N,N-Me-2-Dmt-Tic-Ala-OH (15) also augmented delta opioid receptor binding, such that 15 demonstrated high affinity (K-i(delta) = 0.0755 nM) and selectivity (K-i(mu)/K-i(delta) = 20 132) with exceptional antagonist activity on MVD (pA(2) = 9.6; K-e = 0.22 nM) and weak antagonism on GPI (pA(2) = 5.8; K-e = 1.58 mu M; GPI/MVD = 1:7180). Although the amidated dimethylated dipeptide analogue 14 had high K-i(delta) (0.31 nM) and excellent antagonist activity (pA(2) = 9.9; K-e = 0.12 nM), the increased activity toward mu receptors in the absence of a free acid function at the C-terminus revealed modest delta selectivity (K-i(mu)/K-i(delta) = 1 655) and somewhat comparable bioactivity (GPI/MVD = 4500). Thus, the data demonstrate that N,N-(Me)(2)-Dmt-Tic-OH (12) and N,N-Me-2-Dmt-Tic-Ala-OH (15) retained high delta receptor affinities and delta selectivities and acquired enhanced potency in pharmacological bioassays on MVD greater than that of other peptide or non-peptide delta antagonists.

  DOI：

  10.1021/jm9607663

文献信息

• PREPARATION OF QUINAPRIL HYDROCHLORIDE
  申请人：——

  公开号：US20040192613A1

  公开（公告）日：2004-09-30

  Methods and materials for preparing quinapril, its pharmaceutically acceptable salts, including quinapril hydrochloride, are disclosed. The method includes reacting (2S,4S)-2-(4-methyl-2,5-dioxo-oxazolidin-3-yl)-4-phenyl-butyric acid ethyl ester with (3S)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid tert-butyl ester to yield quinapril tert-butyl ester, which is subsequently reacted with an acid to yield quinapril or an acid addition salt of quinapril.

  制备喹那普利及其可药用盐的方法和材料被公开，包括喹那普利盐酸盐。该方法包括将(2S,4S)-2-(4-甲基-2,5-二氧代恶唑烷-3-基)-4-苯基丁酸乙酯与(3S)-1,2,3,4-四氢异喹啉-3-羧酸叔丁酯反应，得到喹那普利叔丁酯，随后与酸反应，得到喹那普利或喹那普利的酸加成盐。
• [EN] CXCR3 RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RÉCEPTEUR CXCR3
  申请人：CELGENE INT II SARL

  公开号：WO2018045246A1

  公开（公告）日：2018-03-08

  Compounds are provided having the structure of the following Formula I: where R, R1, R2, R3a and R3b are as defined herein. Pharmaceutical compositions comprising such compounds, as well as methods related to their manufacture and use, are also provided.

  提供具有以下式I结构的化合物：其中R、R1、R2、R3a和R3b如本文所述定义。还提供了包含这些化合物的药物组合物，以及与它们的制造和使用相关的方法。
• Studies on angiotensin-converting enzyme inhibitors. I. Syntheses and angiotensinconverting enzyme inhibitory activity of 2-(3-mercaptopropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives.
  作者：KIMIAKI HAYASHI、YASUHIKO OZAKI、KENICHI NUNAMI、TOMOFUMI UCHIDA、JYOJI KATO、KEIZO KINASHI、NAOTO YONEDA

  DOI：10.1248/cpb.31.570

  日期：——

  (3S)-2-[(2S)-3-Mercapto-2-methylpropionyl]-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid [(3S), (2S)-6a] was prepared by the reaction of (3S)-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid tert-butyl ester [(3S)-2a] or benzyl ester [(3S)-2b] with 3-benzoylthio-2-methylpropionyl chloride (3a), followed by fractional crystallization and removal of the protective group. The absolute configuration of (3S), (2S)-6a was confirmed by X-ray diffraction analysis of the thiazepino [4, 3-b] isoquinoline compound (7) derived from 6a. Resolution of 3-benzoylthio-2-methylpropionic acid (8) was completed by using optically active phenylalanine amide as a resolving agent. The other optical isomers of (3S), (2S)-6a were prepared by the reaction of (3S)- or (3R)-2b with optically active 3a. The in vitro ACE inhibitory activity of each isomer of 6a was evaluated. Among them, (3S), (2S)-6a was found to be the most potent inhibitor with an IC50 value of 8.6×10-9M. Compound (3S), (2S)-6a induced a dose-dependent inhibition of the pressor response to angiotensin I after oral administration to normotensive anesthetized rats. Moreover, (3S), (2S)-6a markedly reduced the systolic blood pressure in renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). The in vivo ACE inhibitory activity and the hypotensive effects of (3S), (2S)-6a were comparable to those of captopril.

  (3S)-2-[(2S)-3-巯基-2-甲基丙酰基]-1, 2, 3, 4-四氢异喹啉-3-羧酸[(3S), (2S)-6a]是通过(3S)-1, 2, 3, 4-四氢异喹啉-3-羧酸叔丁基酯[(3S)-2a]或苄基酯[(3S)-2b]与3-苯甲酰硫-2-甲基丙酰氯(3a)反应制备而成，随后通过分馏结晶去除保护基团。通过对由6a衍生的噻唑烯[4, 3-b]异喹啉化合物(7)进行X射线衍射分析，确认了(3S), (2S)-6a的绝对构型。使用光学活性的苯丙氨酸酰胺作为分解剂完成了3-苯甲酰硫-2-甲基丙酸(8)的分解。通过(3S)-或(3R)-2b与光学活性3a反应制备了(3S), (2S)-6a的其他光学异构体。评估了每种6a异构体的体外ACE抑制活性。其中，(3S), (2S)-6a被发现是最有效的抑制剂，IC50值为8.6×10^-9M。化合物(3S), (2S)-6a在该显混合型麻醉大鼠口服给药后，诱导了对血管紧张素I的加压反应的剂量依赖性抑制。此外，(3S), (2S)-6a显著降低了肾性高血压大鼠(RHR)和自发性高血压大鼠(SHR)的收缩压。(3S), (2S)-6a的体内ACE抑制活性和降压效果与卡托普利相当。
• Role of 2′,6′-dimethyl-l-tyrosine (Dmt) in some opioid lead compounds
  作者：Gianfranco Balboni、Erika Marzola、Yusuke Sasaki、Akihiro Ambo、Ewa D. Marczak、Lawrence H. Lazarus、Severo Salvadori

  DOI：10.1016/j.bmc.2010.06.073

  日期：2010.8

  H-Tyr-Tic-Asp∗-Bid are potent and selective δ antagonists (pA2 = 8.95 and 8.85, respectively). When these amino acids are employed in the synthesis of deltorphin B and its Dmt1 and Dft1 analogues, the three compounds maintain a very similar δ agonism (MVD, IC50 0.32–0.53 nM) with a decrease in selectivity relative to the Dmt1 analogue. In the less selective H-Dmt-Tic-Gly∗-Bid the replacement of Dmt with Dft and

  在这里，我们评估了氨基酸 2',6'-二甲基-l-酪氨酸 (Dmt)、2',6'-二氟-l-酪氨酸 (Dft) 和1 位酪氨酸的互换如何影响药理学表征一些参考阿片肽和假肽。通常，尽管 p K a值不同，但 Dft 和 Tyr 提供具有相似药理学特征的类似物。Dmt/Tyr(Dft) 替换会根据进行修改的参考阿片类药物产生活性变化。然而，H-Dmt-Tic-Asp*-Bid 是一种有效的选择性 δ 激动剂（MVD，IC 50  = 0.12 nM）；H-Dft-Tic-Asp∗-Bid 和 H-Tyr-Tic-Asp∗-Bid 是有效的选择性 δ 拮抗剂 (pA 2 = 8.95 和 8.85，分别）。当这些氨基酸用于合成 deltorphin B 及其 Dmt 1和 Dft 1类似物时，这三种化合物保持非常相似的 δ 激动作用（MVD，IC 50 0.32–0.53 nM），而选择性相对于
• Synthesis and biological activity of modified peptide inhibitors of angiotensin-converting enzyme
  作者：W. Howard Roark、Francis J. Tinney、David Cohen、Arnold D. Essenburg、Harvey R. Kaplan

  DOI：10.1021/jm00147a030

  日期：1985.9

  substituted for the amino group and in which the proline residue has been replaced with various hydrophobic amino acids. The compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme and in vivo for antihypertensive activity. Compound 7c, the most potent member of this series, had an in vitro IC50 of 1.4 X 10(-8) M and showed modest oral antihypertensive activity at 30 mg/kg in conscious

  制备了一系列与CI-906，CI-907和依那普利有关的非巯基修饰的二肽，其中各种等位异构部分（O，S，SO，SO2）已取代了氨基，且脯氨酸残基具有被各种疏水性氨基酸取代。在体外评估该化合物对血管紧张素转化酶的抑制作用，在体内评估其抗高血压活性。化合物7c是该系列中最有效的成员，其体外IC50为1.4 X 10（-8）M，并且在有意识的两只肾脏，一只夹子Goldblatt高血压大鼠中以30 mg / kg的剂量显示适度的口服降压活性。讨论了构效关系。