7-amino-1-methyl-3,4-dihydroquinolin-2(1H)-one | 813424-19-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-amino-1-methyl-3,4-dihydroquinolin-2(1H)-one
• 英文别名: 7-amino-1-methyl-3,4-dihydroquinolin-2-one
• CAS: 813424-19-0
• 化学式: C₁₀H₁₂N₂O
• mdl: MFCD09880363
• 分子量: 176.218
• InChiKey: SOKTXJGBXRRDGK-UHFFFAOYSA-N

物化性质

• 沸点：
  459.5±45.0 °C(Predicted)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-amino-1-methyl-3,4-dihydroquinolin-2(1H)-one 、 2-氟-4-(三氟甲基)苯甲酰氯 在 吡啶 作用下， 反应 12.0h， 生成 2-fluoro-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-4-(trifluoromethyl)benzamide
  参考文献：
  名称：

  2-AMINOBENZAMIDE DERIVATIVES AS VANILLOID RECEPTOR 1 (VR1) INHIBITORS USEFUL FOR THE TREATMENT OF PAIN OR BLADDER FUNCTION DISORDER

  摘要：

  公开号：

  EP1955697B1
• 作为产物：
  描述：

  7-氨基-3,4-二氢-1H-喹啉-2-酮 在 potassium carbonate 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 7-amino-1-methyl-3,4-dihydroquinolin-2(1H)-one
  参考文献：
  名称：

  Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor

  摘要：

  The bromodomain containing proteins TRIM24 (tripartite motif containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are involved in the epigenetic regulation of gene expression and have been implicated in human cancer. Overexpression of TRIM24 correlates with poor patient prognosis, and BRPF1 is a scaffolding protein required for the assembly of histone acetyltransferase complexes, where the gene of MOZ (monocytic leukemia zinc finger protein) was first identified as a recurrent fusion partner in leukemia patients (8p11 chromosomal rearrangements). Here, we present the structure guided development of a series of N,N-dimethyl-benzimidazolone bromodomain inhibitors through the iterative use of X-ray cocrystal structures. A unique binding mode enabled the design of a potent and selective inhibitor 8i (IACS-9571) with low nanomolar affinities for TRIM24 and BRPF1 (ITC K-d = 31 nM and ITC K-d = 14 nM, respectively). With its excellent cellular potency (EC50 = 50 nM) and favorable pharmacokinetic properties (F = 29%), 8i is a high-quality chemical probe for the evaluation of TRIM24 and/or BRPF1 bromodomain function in vitro and in vivo.

  DOI：

  10.1021/acs.jmedchem.5b00405

文献信息

• [EN] TRPV1 ANTAGONISTS<br/>[FR] ANTAGONISTES DE TRPV1
  申请人：ABBVIE INC

  公开号：WO2013096226A1

  公开（公告）日：2013-06-27

  Disclosed herein are compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein X1, L, Rx, Ry, G, Z, A, m, n, and p are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed. The compounds of formula (I) are useful as TRPV1 antagonists.

  披露了公式(I)的化合物：或其药用可接受的盐，其中X1、L、Rx、Ry、G、Z、A、m、n和p如说明书所述。还披露了包含这些化合物的组合物，以及使用这些化合物和组合物治疗状况和失调的方法。公式(I)的化合物作为TRPV1拮抗剂是有用的。
• TRPV1 Antagonists
  申请人：Gomtsyan Arthur

  公开号：US20120245163A1

  公开（公告）日：2012-09-27

  Disclosed herein are compounds of formula (I) or pharmaceutically acceptable salts, solvates, or combinations thereof, wherein X 1 , X 2 , X 3 , X 4 , J, K, L, X 5 , X 6 , R b , G 2 , and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

  本文揭示了具有以下式（I）的化合物或药用可接受的盐、溶剂或其组合物，其中X1、X2、X3、X4、J、K、L、X5、X6、Rb、G2和m在规范中有定义。还披露了包含这些化合物的组合物以及使用这些化合物和组合物治疗疾病和疾病的方法。
• Design, synthesis, and biological evaluation of novel biphenyl-4-carboxamide derivatives as orally available TRPV1 antagonists
  作者：Hiromasa Oka、Koichi Yonezawa、Akio Kamikawa、Kazuhiro Ikegai、Norio Asai、Shohei Shirakami、Satoshi Miyamoto、Toshihiro Watanabe、Tetsuo Kiso、Yukihiro Takemoto、Seiji Tamura、Takahiro Kuramochi

  DOI：10.1016/j.bmc.2018.06.001

  日期：2018.7

  A new series of transient receptor potential vanilloid type 1 (TRPV1) antagonists were designed and synthesized from N-(3-hydroxyphenyl)-2-(piperidin-1-ylmethyl)biphenyl-4-carboxamide hydrochloride (8). SAR studies identified (R)-N-(1-methyl-2-oxo-1,2,3,4-tetrahydro-7-quinolyl)-2-[(2-methylpyrrolidin-1-yl)methyl]biphenyl-4-carboxamide hydrochloride (ASP8370, 7), as a compound with high aqueous solubility

  从N-（3-羟苯基）-2-（哌啶-1-基-甲基）联苯-4-甲酰胺盐酸盐（8）设计并合成了一系列新的瞬态受体电位香草酸1型（TRPV1）拮抗剂。SAR研究确定了（R）-N-（1-甲基-2-氧代-1,2,3,4-四氢-7-喹啉基）-2-[（（2-甲基吡咯烷-1-基）甲基]联苯-4甲酰胺盐酸盐（ASP8370，7），是一种具有高水溶性的化合物，在人肝微粒体中具有令人满意的稳定性，并降低了CYP3A4的抑制作用。选择ASP8370作为对神经性疼痛有明显改善作用的临床开发候选药物。SAR研究还揭示了TRPV1拮抗作用与激动作用之间转换的潜在机制。
• 2-AMINOBENZAMIDE DERIVATIVE
  申请人：Kuramochi Takahiro

  公开号：US20090233900A1

  公开（公告）日：2009-09-17

  To provide a novel and excellent agent for treating or preventing nociceptive pain, neuropathic pain, cancer pain, headache, bladder function disorder and the like, based on the inhibitory action on the capsaicin receptor VR1 activation. The present invention was accomplished by confirming that a benzamide derivative characterized by the possession of a benzene ring in which a single ring is condensed on the nitrogen atom of amido group and possession of a lower alkylamino or an amino group substituted with a ring group at the neighboring position of said amido group has a strong inhibitory action on VR1 activation and excellent pharmacological actions based on this and by finding that it can become an excellent agent for treating or preventing VR1-involved diseases such as nociceptive pain, neuropathic pain, cancer pain, headache, bladder function disorder and the like.

  本发明提供了一种基于对辣椒素受体VR1激活的抑制作用的新型优良药剂，用于治疗或预防伤害性疼痛、神经病理性疼痛、癌症疼痛、头痛、膀胱功能障碍等疾病。本发明通过确认一种苯甲酰胺衍生物，其特征在于其苯环上的单环在酰胺基氮原子上被紧缩，其低烷基氨基或邻位于酰胺基的环基取代的氨基具有对VR1激活的强抑制作用和优良的药理作用，从而发现它可以成为治疗或预防伤害性疼痛、神经病理性疼痛、癌症疼痛、头痛、膀胱功能障碍等VR1相关疾病的优良药剂。
• HETEROCYCLIDENE-N-(ARYL) ACETAMIDE DERIVATIVE
  申请人：UCHIDA Hideharu

  公开号：US20100016285A1

  公开（公告）日：2010-01-21

  The blow-described formula (I) [Ch. 1] a compound represented by formula (I) (wherein k, m, n, and p each represent 0 to 2; j and q represents 0 or 1; R 1 represents a halogen atom, a hydrocarbon group, a heterocyclic group, an alkoxy group, an alkoxycarbonyl group, NH 2 , OH, a carboxyl group, an alkanoyl group, CN, NO 2 , or the like; R 2 represents a halogen atom, an amino group, a hydrocarbon group, an aromatic heterocyclic group, an oxo group, or the like; represents an oxygen atom, —NR 3 —, or —S(O)r- (wherein r is an integer of 0 to 2); X 2 represents a methylene group, an oxygen atom, —NR 3 — (wherein R 3 is a hydrogen atom, a hydrocarbon group, or the like), or S(O)r- (wherein r is an integer of 0 to 2); W represents a methylene group, a carbonyl group, or a sulfonyl group; R 7 represents a hydrogen atom, a hydrocarbon group, a heterocyclic group, or the like; R 8 represents a hydrogen atom, a halogen atom, a hydrocarbon group, a heterocyclic group, the broken line in the ring containing X 1 and X 2 represents a condensation of two rings; cycle moiety represents a five- or six-membered aryl ring or heteroaryl ring; and the solid line and the broken line between L 1 and L 2 are a single bond or double bond, and the wavy line represents an E-isomer or a Z-isomer), a salt thereof, or solvates thereof, and a pharmaceutical composition containing the compound as an active ingredient.

  以下是所描述的公式(I)[Ch. 1]的化合物，由公式(I)表示（其中k、m、n和p各自表示0到2；j和q表示0或1；R1表示卤素原子、碳氢基团、杂环基团、烷氧基、烷氧羰基基团、NH2、OH、羧基、烷酰基、CN、NO2或类似物；R2表示卤素原子、氨基基团、碳氢基团、芳香杂环基团、氧代基团或类似物；表示氧原子、-NR3-或-S（O）r-（其中r为0至2的整数）；X2表示亚甲基基团、氧原子、-NR3-（其中R3为氢原子、碳氢基团或类似物）或S（O）r-（其中r为0至2的整数）；W表示亚甲基基团、羰基基团或磺酰基基团；R7表示氢原子、碳氢基团、杂环基团或类似物；R8表示氢原子、卤素原子、碳氢基团、杂环基团，环中的X1和X2之间的断线表示两个环的缩合；环基表示五元或六元芳基环或杂芳基环；实线和L1和L2之间的断线是单键或双键，波浪线表示E-异构体或Z-异构体），其盐或溶剂化物，以及含有该化合物作为活性成分的药物组成物。