2-甲基-吡唑并[1,5-A]嘧啶-6-羧胺 | 338953-49-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 2-甲基-吡唑并[1,5-A]嘧啶-6-羧胺
• 英文名称: 2-methylpyrazolo[1,5-a]pyrimidine-6-carboxylic acid amide
• 英文别名: 2-Methylpyrazolo[1,5-a]pyrimidine-6-carboxamide
• CAS: 338953-49-4
• 化学式: C₈H₈N₄O
• mdl: MFCD00794595
• 分子量: 176.178
• InChiKey: JAYAPPQABNWHQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-甲基-吡唑并[1,5-A]嘧啶-6-羧胺 在 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以63%的产率得到阿拉格列汀
  参考文献：
  名称：

  Discovery and pharmacological characterization of N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor

  摘要：

  In the course of our program for discovery of novel DPP-IV inhibitors, a series of pyrazolo[1,5-a]pyrimidines were found to be novel DPP-IV inhibitors. We identified N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (4a) and described its pharmacological profiles. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.043

文献信息

• [EN] N-[2-(1 -BENZYLPIPERIDIN-4-YL)ETHYL]-4-(PYRAZIN-2-YL)-PIPERAZINE-1 -CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MUSCARINIC RECEPTOR 4 (M4) ANTAGONISTS FOR TREATING NEUROLOGICAL DISEASES<br/>[FR] DÉRIVÉS DE N-[2-(1-BENZYLPIPÉRIDIN-4-YL)ÉTHYL]-4-(PYRAZIN-2-YL)-PIPÉRAZINE-1-CARBOXAMIDE ET COMPOSÉS APPARENTÉS EN TANT QU'ANTAGONISTES DU RÉCEPTEUR MUSCARINIQUE 4 (M4) POUR LE TRAITEMENT DE MALADIES NEUROLOGIQUES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2017079641A1

  公开（公告）日：2017-05-11

  Provided herein are small molecule compounds of the following formula (I): or a stereoisomer, tautomer, solvate, ester or pharmaceutically acceptable salt thereof, wherein A, B, C, Li, L 2, Ri, R 2, R 3, R 4, R 5, w, x, y and z are as defined herein. Methods for treating diseases/ disorders by antagonizing muscarinic receptors, including specifically antagonizing muscarinic receptor 4 (M4), are also disclosed. Such diseases/disorders are e.g. neurological diseases/disorders such as e.g. Alzheimer's Disease, Lewy Body Dementia and the cognitive deficits associated with schizophrenia, Parkinson's Disease, drug induced Parkinsonism, dyskinesias, dystonia, chorea, levodopa induced dyskinesia, cerebral palsy, progressive supranuclear palsy, and Huntington's disease. Preferred compounds are e.g. N-[2-(l-benzylpiperidin-4-yl)ethyl]-4- (pyrazin-2-yl)-piperazine-1-carboxamide derivatives and related compounds wherein the pyrazine has been replaced by e.g. pyridazine, pyrimidine, pyridine or phenyl.

  本文提供了以下化学式（I）的小分子化合物，或其立体异构体、互变异构体、溶剂化合物、酯或药用可接受的盐，其中A、B、C、Li、L 2、Ri、R 2、R 3、R 4、R 5、w、x、y和z的定义如本文所述。还公开了通过拮抗毒蕈碱受体来治疗疾病/障碍的方法，包括特别是拮抗毒蕈碱受体4（M4）。这些疾病/障碍包括神经系统疾病/障碍，如阿尔茨海默病、路易体痴呆症以及与精神分裂症、帕金森病、药物引起的帕金森综合症、运动障碍、肌张力障碍、舞蹈症、左多巴诱发的运动障碍、脑瘫、进行性核上性麻痹和亨廷顿病相关的认知缺陷等。首选化合物是例如N-[2-(1-苄基哌啶-4-基)乙基]-4-(吡嗪-2-基)-哌嗪-1-甲酰胺衍生物和相关化合物，其中吡嗪已被取代为例如吡啶、嘧啶、吡啶或苯基。
• Compound inhibiting dipeptidyl peptidase IV
  申请人：Kakigami Takuji

  公开号：US20060229286A1

  公开（公告）日：2006-10-12

  A dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. A compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R 1 and R 2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or —COOR 5 whereupon R 5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R 1 , R 2 , and a carbon atom together represent a 3- to 6-membered cycloalkyl group, R 3 represents hydrogen or an optionally substituted C6-10 aryl group, R 4 represents a hydrogen or a cyano group, D represents —CONR 6 —, —CO— or —NR 6 CO—, R 6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents —(CH 2 ) m — whereupon m is 1 to 3, —CH 2 OCH 2 —, or —SCH 2 —, n is 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.

  一种二肽基肽酶IV抑制剂，具有活性、稳定性和安全性方面的满意度，并且作为药物剂量具有优异的作用。该化合物由以下通式表示或其药学上可接受的盐：其中R1和R2分别表示氢、可选取代的C1-6烷基或-COOR5，其中R5表示氢或可选取代的C1-6烷基，或者R1、R2和一个碳原子共同表示3-6个成员的环烷基，R3表示氢或可选取代的C6-10芳基，R4表示氢或氰基，D表示-CONR6-、-CO-或-NR6CO-，R6表示氢或可选取代的C1-6烷基，E表示-(CH2)m-，其中m为1至3，- O -或-S -，n为0至3，A表示可选取代的双环杂环基或双环烃基。
• COMPOUND INHIBITING DIPEPTIDYL PEPTIDASE IV
  申请人：SANWA KAGAKU KENKYUSHO CO., LTD.

  公开号：EP1595866A1

  公开（公告）日：2005-11-16

  The invention aims to provide a dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. The invention is directed to a compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R1 and R2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or -COOR5 whereupon R5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R1 and R2, together with a carbon atom to which they are bound, represent a 3- to 6-membered cycloalkyl group, R3 represents hydrogen or an optionally substituted C6-10 aryl group, R4 represents a hydrogen or a cyano group, D represents -CONR6-, -CO- or -NR6CO-, R6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents -(CH2)m- whereupon m is an integer of 1 to 3, -CH2OCH2-, or -SCH2-, n is an integer of 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.

  本发明旨在提供一种二肽基肽酶 IV 抑制剂，该抑制剂在活性、稳定性和安全性方面都令人满意，并且作为药剂具有出色的作用。本发明涉及由以下通式代表的化合物或其药学上可接受的盐： 其中 R1 和 R2 各自代表氢、任选取代的 C1-6 烷基或 -COOR5 其中 R5 代表氢或任选取代的 C1-6 烷基，或 R1 和 R2 与它们结合的碳原子一起代表 3 至 6 元环烷基，R3 代表氢或任选取代的 C6-10 芳基、R4代表氢或氰基，D代表-CONR6-、-CO-或-NR6CO-，R6代表氢或任选取代的C1-6烷基，E代表-(CH2)m-，其中m为1至3的整数，- O -或-S -，n为0至3的整数，A代表任选取代的双环杂环基团或双环烃基团。
• Compounds of formulas (VII), (VIII), (IX), (XI), (XII), (XIII), and (XIV) as muscarinic receptor 4(M4) antagonists for treating neurological diseases
  申请人：Neurocrine Biosciences, Inc.

  公开号：US11033539B2

  公开（公告）日：2021-06-15

  Provided herein are small molecule compounds of the following formula (I): or a stereoisomer, tautomer, solvate, ester or pharmaceutically acceptable salt thereof, wherein A, B, C, L1, L2, R2, R3, R4, R3, w, x, y and z are as defined herein. Methods for treating diseases/disorders by antagonizing muscarinic receptors, including specifically antagonizing muscarinic receptor 4 (M4), are also disclosed. Such diseases/disorders are e.g. neurological diseases/disorders such as e.g. Alzheimer's Disease, Lewy Body Dementia and the cognitive deficits associated with schizophrenia, Parkinson's Disease, drug induced Parkinsonism, dyskinesias, dystonia, chorea, levodopa induced dyskinesia, cerebral palsy, progressive supranuclear palsy, and Huntington's disease. Preferred compounds are e.g. N-[2-(1-benzylpiperidin-4-yl)ethyl]-4-(pyrazin-2-yl)-piperazine-1-carboxamide derivatives and related compounds wherein the pyrazine has been replaced by e.g. pyridazine, pyrimidine, pyridine or phenyl.

  本文提供了下式（I）的小分子化合物：或其立体异构体、同分异构体、溶液剂、酯或药学上可接受的盐，其中 A、B、C、L1、L2、R2、R3、R4、R3、w、x、y 和 z 如本文所定义。还公开了通过拮抗毒蕈碱受体（包括特异性拮抗毒蕈碱受体 4 (M4)）来治疗疾病/紊乱的方法。此类疾病/障碍包括神经系统疾病/障碍，例如阿尔茨海默病、路易体痴呆和与精神分裂症相关的认知障碍、帕金森病、药物诱发的帕金森症、运动障碍、肌张力障碍、舞蹈症、左旋多巴诱发的运动障碍、脑性麻痹、进行性核上性麻痹和亨廷顿氏病。首选化合物为 N-[2-(1-苄基哌啶-4-基)乙基]-4-(吡嗪-2-基)-哌嗪-1-甲酰胺衍生物及相关化合物，其中吡嗪已被哒嗪、嘧啶、吡啶或苯基等取代。
• Activator of TREK (TWIK RElated K+ channels) channels
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US11046683B2

  公开（公告）日：2021-06-29

  Disclosed is a compound of formula (I): wherein all symbols are defined in the description. Also disclosed are pharmaceutical compositions comprising the compounds, methods of making the compounds, kits comprising the compounds, and methods of using the compounds, compositions and kits for treatment of disorders associated with TREK-1, TREK-2 or both TREK-1 and TREK-2 dysfunction in a mammal.

  本发明公开了一种式 (I) 的化合物： 其中所有符号在描述中定义。还公开了包含所述化合物的药物组合物、制造所述化合物的方法、包含所述化合物的试剂盒，以及使用所述化合物、组合物和试剂盒治疗哺乳动物中与 TREK-1、TREK-2 或 TREK-1 和 TREK-2 功能障碍相关的疾病的方法。