ethyl 2-(7-methoxy-3,4-dihydro-naphthalen-2-yl)acetate | 99318-10-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 2-(7-methoxy-3,4-dihydro-naphthalen-2-yl)acetate
• 英文别名: Ethyl 2-(7-methoxy-3,4-dihydronaphthalen-2-yl)acetate
• CAS: 99318-10-2
• 化学式: C₁₅H₁₈O₃
• 分子量: 246.306
• InChiKey: BMBRXHIBRARXAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-(7-methoxy-3,4-dihydro-naphthalen-2-yl)acetate 在 四氯苯醌 作用下， 以 xylene 为溶剂， 反应 1.5h， 以48%的产率得到ethyl (7-methoxy-2-naphthalenyl)acetate
  参考文献：
  名称：

  New Platelet Fibrinogen Receptor Glycoprotein IIb-IIIa Antagonists:  Orally Active Series of N-Alkylated Amidines with a 6,6-Bicyclic Template

  摘要：

  The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholino-formimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3-yl]acetate hydrochloride ((S)-4 . HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3,4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4 . HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4 . HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4 . HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.

  DOI：

  10.1021/jm9801859
• 作为产物：
  描述：

  7-甲氧基-1-萘满酮 在 sodium tetrahydroborate 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 碳酸氢钠 、 间氯过氧苯甲酸 、 zinc(II) iodide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 甲苯 、 苯 为溶剂， 反应 11.0h， 生成 ethyl 2-(7-methoxy-3,4-dihydro-naphthalen-2-yl)acetate
  参考文献：
  名称：

  New Platelet Fibrinogen Receptor Glycoprotein IIb-IIIa Antagonists:  Orally Active Series of N-Alkylated Amidines with a 6,6-Bicyclic Template

  摘要：

  The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholino-formimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3-yl]acetate hydrochloride ((S)-4 . HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3,4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4 . HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4 . HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4 . HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.

  DOI：

  10.1021/jm9801859

文献信息

• Potential Antidepressants Displayed Combined α₂-Adrenoceptor Antagonist and Monoamine Uptake Inhibitor Properties
  作者：Alex A. Cordi、Isabelle Berque-Bestel、Thierry Persigand、Jean-Michel Lacoste、Adrian Newman-Tancredi、Valerie Audinot、Mark J. Millan

  DOI：10.1021/jm001040g

  日期：2001.3.1

  chosen as a point of departure for the design of 4(5)-[(3,4-dihydro-2-naphthalenyl)methyl]-4,5-dihydroimidazole (4a), which displayed the desired profile: alpha(2A)-adrenoceptor antagonist properties and serotonin/noradrenaline uptake inhibition. From this original molecule, a series of derivatives was designed and synthesized, encompassing substituted as well as rigid analogues. Structure-activity relationships

  人们认为经典的抗抑郁药通过提高大脑中的单胺（5-羟色胺和去甲肾上腺素）水平来发挥作用。通常通过抑制单胺代谢（MAO抑制剂）或阻断单胺摄取（三环类抗抑郁药和选择性5-羟色胺或去甲肾上腺素再摄取抑制剂）来完成该作用。但是，所有此类药物均存在时滞（3--6周），才能证明其强大的临床功效。此延迟可能反映了去甲肾上腺素对突触前α（2A）-肾上腺素能自发或异源受体的抑制作用，该抑制作用在长时间暴露下会逐渐下调。具有单胺摄取抑制特性的拮抗剂对突触前α（2A）-肾上腺素受体的阻断作用可能导致新的抗抑郁药具有更高的疗效和更短的时间延迟。在文献中 仅描述了两个具有这种药理学特征的分子。其中，萘哌唑（2）被选为设计4（5）-[（（3,4-二氢-2-萘基）甲基] -4,5-二氢咪唑（4a）的起点。所需的配置文件：α（2A）-肾上腺素受体拮抗剂特性和5-羟色胺/去甲肾上腺素摄取抑制。从这个原始分子，设计并合成了一系
• Heterocyclic aryl-, alkyl- and cycloalkylacetamides
  申请人：Bayer Aktiengesellschaft

  公开号：US05747505A1

  公开（公告）日：1998-05-05

  The heterocyclic aryl-, alkyl- and cycloalklacetamides are prepared by reacting the appropriately substituted acetic acids with amines, if appropriate in complexed form. The heterocyclic aryl-, alkyl- and cycloalkylacetamides can be used as active compounds in medicaments, in particular in antiatherosclerotic medicaments.

  通过将适当取代的乙酸与胺反应制备杂环芳基、烷基和环烷基乙酰胺，如果需要可以以络合形式进行。这些杂环芳基、烷基和环烷基乙酰胺可用作药物中的活性化合物，特别是用于抗动脉粥样硬化药物。
• 1-OMEGA-(3,4-DIHYDRO-2-NAPHTHALENYL)ALKYL] CYCLIC AMINE DERIVATIVES, PROCESS FOR PRODUCING THE SAME, AND MEDICINAL COMPOSITION CONTAINING THE SAME
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：EP0825180A1

  公开（公告）日：1998-02-25

  1-[ω-(3,4-Dihydro-2-naphthalenyl)alkyl] cyclic amine derivatives represented by general formula (I) and salts and N-oxide derivatives thereof, wherein R1 and R2 represent each hydrogen, halogeno, hydroxy, alkyl, alkoxy, hydroxymethyl, etc., or R1 and R2 form together methylenedioxy, trimethylene, etc.; R3 represents hydrogen, etc.; R4 represents hydrogen, hydroxy, alkyl, etc.; R5 represents hydrogen, alkyl, etc.; p is an integer of from 2 to 6; and q is an integer of from 3 to 7; excluding the case where R1, R2, R3, R4 and R5 are all hydrogen, p is 2 and q is 5. The compounds have a potent effect of suppressing urinary reflex and thus are useful as a remedy for frequent urination and urinary incontinence.

  通式(I)代表的 1-[ω-(3,4-二氢-2-萘基)烷基]环胺衍生物及其盐和 N-氧化物衍生物，其中 R1 和 R2 各自代表氢、卤素、羟基、烷基、烷氧基、羟甲基等、或 R1 和 R2 共同形成亚甲基二氧基、三亚甲基等；R3 代表氢等；R4 代表氢、羟基、烷基等；R5 代表氢、烷基等；p 为 2 至 6 的整数；q 为 3 至 7 的整数；不包括 R1、R2、R3、R4 和 R5 均为氢的情况，p 为 2，q 为 5。这些化合物具有抑制排尿反射的强效作用，因此可用于治疗尿频和尿失禁。
• 一种并环类衍生物及其制备方法和医药用途
  申请人：深圳信立泰药业股份有限公司

  公开号：CN115594669A

  公开（公告）日：2023-01-13

  本发明属于化学药物技术领域，涉及式(I)的化合物、其制备方法及其在医药上的应用。具体而言，本发明提供式(I)的化合物或其立体异构体、互变异构体、药学上可接受的盐。这些化合物是胰高血糖样肽‑1受体(GLP‑1R)的激动剂。本发明还涉及包含这些化合物的药物组合物以及使用该化合物治疗糖尿病等疾病的药物中的用途。
• STRASSER, MICHAEL;COOPER, PHILIP;DEWALD, BEATRICE;PAYNE, TREVOR, HELV. CHIM. ACTA, 71,(1988) N 5, C. 1156-1176
  作者：STRASSER, MICHAEL、COOPER, PHILIP、DEWALD, BEATRICE、PAYNE, TREVOR

  DOI：——

  日期：——