3-Isoquinolinecarboxylic acid, 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-, methyl ester, sulfate (1:1) | 212500-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-Isoquinolinecarboxylic acid, 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-, methyl ester, sulfate (1:1)
• 英文别名: methyl 2-(4-aminophenyl)-1-oxo-7-(pyridin-2-ylmethoxy)-4-(3,4,5-trimethoxyphenyl)isoquinoline-3-carboxylate;sulfuric acid
• CAS: 212500-03-3
• 化学式: C32H31N3O11S
• 分子量: 665.7
• InChiKey: NVGOUBIJVPSVSL-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO：23 mg/mL，可溶

计算性质

• 辛醇/水分配系数(LogP)：
  4.37
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  205
• 氢给体数：
  3
• 氢受体数：
  13

文献信息

• [EN] ISOQUINOLINONE DERIVATIVES, PROCESS FOR PREPARING THE SAME, AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS<br/>[FR] DERIVES D'ISOQUINOLINONE, PROCEDE DE PREPARATION DESDITS DERIVES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PHOSPHODIESTERASE
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：WO1998038168A1

  公开（公告）日：1998-09-03

  (EN) An isoquinolinone derivative of formula (I) wherein Ring A and Ring B are substituted or unsubstituted benzene, R1 is (1) H, (2) substituted or unsubstituted lower alkyl, (3) substituted or unsubstituted cyclo-lower alkyl, (4) substituted or unsubstituted aryl, (5) substituted or unsubstituted heterocycle, or (6) amino optionally having one or two substitutents, R2 is -COOR3 or -CON(R4)(R5), R3 is H or ester residue, and -N(R4)(R5) is substituted or unsubstituted nitrogen-containing aliphatic heterocycle or substituted or unsubstituted amino, provided that when R1 is H or substituted or unsubstituted lower alkyl, then at least one of Ring A and Ring B is benzene being substituted by two or more lower alkoxy, or a pharmaceutically acceptable salt thereof, these compounds showing cGMP-specific PDE inhibitory activity, especially, selective phosphodiesterase V (PDEV) inhibitory activity, and hence, being useful for the prophylaxis or treatment of various diseases such as chronic heart failure, angina, pulmonary hypertension, erectile dysfunction, etc.(FR) Dérivés d'isoquinolinone de formule (I) dans laquelle le noyau A et le noyau B sont benzène substitué ou non substitué, R1 est (1) H, (2) alkyle inférieur substitué ou non substitué, (3) cycloalkyle inférieur substitué ou non substitué, (4) aryle substitué ou non substitué, (5) hétérocycle substitué ou non substitué ou (6) amino ayant éventuellement un ou deux substituants, R2 est -COOR3 ou -CON(R4)(R5), R3 est H ou un reste ester et -N(R4)(R5) est un hétérocycle aliphatique contenant azote substitué ou non substitué ou amino substitué ou non substitué, à condition que lorsque R1 est H ou alkyle inférieur substitué ou non substitué, au moins l'un des noyaux A et B soit benzène substitué par deux alcoxy inférieur ou plus, ou sel pharmaceutiquement acceptable desdits composés. Lesdits composés présentent une activité d'inhibition de la photodiestérase spécifique de cGMP, en particulier une activité sélective d'inhibition de la phosphodiestérase V, et sont donc utiles pour la prophylaxie ou le traitement de diverses maladies telles que l'insuffisance cardiaque chronique, l'angine de poitrine, l'hypertension pulmonaire, la dysérection, etc.

  (I)式中的异喹啉酮衍生物，其中环A和环B是取代或未取代的苯，R1为(1)H，(2)取代或未取代的低烷基，(3)取代或未取代的环低烷基，(4)取代或未取代的芳基，(5)取代或未取代的杂环，或(6)氨基，可选地具有一个或两个取代基，R2为-COOR3或-CON(R4)(R5)，R3为H或酯残基，而-N(R4)(R5)是取代或未取代的含氮脂肪杂环或取代或未取代的氨基，但当R1为H或取代或未取代的低烷基时，至少有一个环A和环B为取代了两个或更多的低烷氧基的苯，或其药学上可接受的盐。这些化合物显示出cGMP特异性PDE抑制活性，特别是选择性磷酸二酯酶V（PDEV）抑制活性，因此，它们对于预防或治疗各种疾病如慢性心力衰竭、心绞痛、肺动脉高压、勃起功能障碍等是有用的。
• Determination of variants produced upon replication or transcription of nucleic acid sequences
  申请人：Bio-ID Diagnostic Inc.

  公开号：US10036053B2

  公开（公告）日：2018-07-31

  A method of determining whether or not a nucleic acid having an expected sequence or one or more variants of the expected sequence are present in a sample containing nucleic acids after replication, transcription or editing (or other transformation) of a substrate nucleic acid. The method involves deciding an expected sequence likely to be formed in the sample upon the replication, transcription or editing of the substrate nucleic acid, and possible variants of the expected sequence, providing primer pairs for a polymerase chain reaction, reverse transcriptase polymerase chain reaction or ligase chain reaction, carrying out the polymerase chain reaction or reverse transcriptase polymerase chain reaction in one or more steps to form amplicons, and analyzing the amplicons to determining whether or not a nucleic acid having the expected sequence and/or variants are present in the sample. The primers of the primer pairs are designed to anneal to regions of the nucleic acid of the expected sequence and the variants, the regions being selected to reveal unambiguously the presence or absence in the sample of the nucleic acid of the expected sequence or the variants thereof according to the presence or absence of specific amplicons amplified by the primers.

  一种方法，用于确定在底物核酸复制、转录或编辑（或其他转化）后，在含有核酸的样品中是否存在具有预期序列的核酸或预期序列的一个或多个变体。该方法包括确定底物核酸复制、转录或编辑后可能在样品中形成的预期序列以及预期序列的可能变体，为聚合酶链反应、逆转录酶聚合酶链反应或连接酶链反应提供引物对，通过一个或多个步骤进行聚合酶链反应或逆转录酶聚合酶链反应以形成扩增子，分析扩增子以确定样品中是否存在具有预期序列和/或变体的核酸。引物对的引物被设计成与预期序列核酸和变体的区域退火，选择这些区域是为了根据引物扩增出的特定扩增子的存在与否，明确揭示样品中是否存在预期序列的核酸或其变体。
• Formulations and methods of using nitric oxide mimetics against a malignant cell phenotype
  申请人：Queens University at Kingston

  公开号：US20030215528A1

  公开（公告）日：2003-11-20

  The present invention relates to methods and formulations for inhibiting, treating and preventing a malignant cell phenotype, cell, tumor and/or disease. Administration of nitric oxide mimetics, such as low doses, is sufficient to increase, restore or maintain nitric oxide-mediated signaling in cells so that malignant cell phenotypes, cells, tumors and/or diseases are inhibited or prevented. These methods and formulations are particularly useful in treating and preventing cancer in animals.

  本发明涉及抑制、治疗和预防恶性细胞表型、细胞、肿瘤和/或疾病的方法和制剂。一氧化氮模拟物（如低剂量）的施用足以增加、恢复或维持细胞中一氧化氮介导的信号转导，从而抑制或预防恶性细胞表型、细胞、肿瘤和/或疾病。这些方法和制剂尤其适用于治疗和预防动物癌症。
• Schwann cell bridge implants and phosphodiesterase inhibitors to stimulate CNS nerve regeneration
  申请人：——

  公开号：US20030220280A1

  公开（公告）日：2003-11-27

  The use of a composition that elevates intracellular levels of cyclic nucleotide cyclases in combination with phosphodiesterase inhibitors and cell grafts to restore function after CNS injury.

  将一种能提高细胞内环核苷酸环化酶水平的成分与磷酸二酯酶抑制剂和细胞移植结合使用，以恢复中枢神经系统损伤后的功能。
• Combination therapy using antihypertensive agents and endothelin antagonists
  申请人：Queen's University at Kingston

  公开号：US20040063719A1

  公开（公告）日：2004-04-01

  The present invention provides a method for a more efficacious treatment of a vascular condition through the administration of a therapeutically effective amount of a combination of an anti-pressor agent, an endothelin antagonist, and a sex hormone for repetitive cycles of on/off-treatment. In one embodiment, the invention provides a method for the prevention of tolerance induced by an anti-pressor agent via the inclusion of an endothelin antagonist in a combination therapy approach to remodel vascular structure and treat vascular conditions associated with a male or female sexual dysfunction, atherosclerosis, renal failure, hypertension, congestive heart failure, diabetic nephropathy, and diabetic neuropathy. The anti-pressor agent comprises one or more compounds such as prostaglandin-E 1 , an ACE inhibitor, an angiotensin-II receptor antagonist, an &agr; 1 -adrenergic receptor antagonist, a &bgr;-adrenergic receptor antagonist, a calcium channel blocker, an activator of guanylyl cyclase or adenyl cyclase, a phosphodiesterase inhibitor, and hydralazine. The endothelin antagonist comprises one or more compounds such as a peptidal endothelin antagonist, a non-peptidal endothelin antagonist, and an inhibitor of endothelin converting enzyme. Such a combination therapy approach enhances the efficacy of the anti-pressor agent and enables an increase in the frequency and duration of anti-pressor administrations for the long term treatment of vascular conditions.

  本发明提供了一种更有效地治疗血管疾病的方法，通过给予治疗有效量的抗压剂、内皮素拮抗剂和性激素的组合，进行重复周期的开/关治疗。在一个实施方案中，本发明提供了一种通过在联合疗法中加入内皮素拮抗剂来预防由抗压迫剂诱发的耐受性的方法，以重塑血管结构并治疗与男性或女性性功能障碍、动脉粥样硬化、肾功能衰竭、高血压、充血性心力衰竭、糖尿病肾病和糖尿病神经病变相关的血管疾病。抗压剂包括一种或多种化合物，如前列腺素-E 1 ACE抑制剂、血管紧张素-II受体拮抗剂、&agr； 1 -肾上腺素能受体拮抗剂、&bgr;-肾上腺素能受体拮抗剂、钙通道阻滞剂、鸟苷酸环化酶或腺苷酸环化酶激活剂、磷酸二酯酶抑制剂和水合肼。内皮素拮抗剂包括一种或多种化合物，如肽类内皮素拮抗剂、非肽类内皮素拮抗剂和内皮素转化酶抑制剂。这种联合治疗方法提高了抗血管紧张素药物的疗效，并能增加抗血管紧张素药物的用药频率和用药时间，从而达到长期治疗血管疾病的目的。