methyl 4-amino-3-((1r,4r)-3'-oxo-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-4-carboxamido)benzoate | 640271-47-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-amino-3-((1r,4r)-3'-oxo-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-4-carboxamido)benzoate
• CAS: 640271-47-2
• 化学式: C₂₂H₂₂N₂O₅
• 分子量: 394.427
• InChiKey: SWIJGCPXVUIHMU-MRAWUWRDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  107.72
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  trans-3-oxospiro[isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxylic acid 、 3,4-二氨基苯甲酸甲酯 在 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 methyl 4-amino-3-((1r,4r)-3'-oxo-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-4-carboxamido)benzoate 、
  参考文献：
  名称：

  新型，强效和选择性反式-2- [3-氧螺环[异苯并呋喃-1（3H），1'-环己基] -4'-基]苯并咪唑NPY Y5受体拮抗剂的合成及构效关系。

  摘要：

  描述了新型的2- [3-氧杂螺[异苯并呋喃-1（3H），1'-环己基] -4'-基]苯并咪唑NPY Y5受体拮抗剂的合成及其构效关系。通过将取代基并入苯并咪唑核心部分的5位或5位和6位两者中来优化前导化合物2a导致鉴定出5-（5-甲基-1,2,4-恶二唑-2 -基）苯并咪唑（2r：IC（50）= 3.3 nM）和5-（2-甲基四唑-5-基）苯并咪唑（2u：IC（50）= 5.9 nM），两者都是有效的，选择性的和口服的可生物利用的Y5受体拮抗剂。

  DOI：

  10.1016/j.bmcl.2008.08.021

文献信息

• PYRROLO- AND THIAZOLO-PYRIDINE COMPOUNDS, AND METHODS OF USE THEREOF
  申请人：DENG Shaojiang

  公开号：US20080004309A1

  公开（公告）日：2008-01-03

  The present invention relates to novel compounds capable of modulating the stability and/or activity of hypoxia inducible factor (HIF).

  这项发明涉及一种能够调节缺氧诱导因子（HIF）稳定性和/或活性的新化合物。
• Novel benzimidazole derivatives
  申请人：——

  公开号：US20040054177A1

  公开（公告）日：2004-03-18

  The present invention relates to a compound of the formula (I): 1 (wherein A, B, C and D are independently nitrogen or optionally substituted methine; E is nitrogen, methine or hydroxy substituted methine; n is 0 or 1; T, U, V and W are independently nitrogen or optionally substituted methine; X is —N(SO 2 R 4 )—, —N(COR 5 )— or —CO—; Y is —C(R 6 )(R 7 )—, —O— or —N(R 8 )—, provided that the compound (I) when E is nitrogen, n is 0, X is —CO—, and Y is —O— is excluded) and the like, which are useful as an agent for the treatment of various diseases related to NPY, for example cardiovascular disorders such as angina, acute or congestive heart failure, myocardial infarction, hypertension, nephropathy, electrolyte abnormality, vasospasm, arteriosclerosis, etc., central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal, circadian rhythm disorders, schizophrenia, memory impairment, sleep disorders, cognitive impairment, etc., metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia, gout, fatty liver, etc., genital or reproductive disorders such as infertility, preterm labor, sexual dysfunction, etc., gastro-intestinal disorders, respiratory disorder, inflammatory diseases or glaucoma, and the like, also for example, atherosclerosis, hypogonadism, hyperandrogenism, polycystic ovary syndrome (Pickwickian syndrome), hirsutism, gastro-intestinal motility disorder, obesity-related gastro-esophageal reflux, obesity hypoventilation, sleep apnea, inflammation, systemic inflammation of the vasculature, osteoarthritis, insulin resistance, bronchoconstriction, alcohol preference, metabolic syndrome, Alzheimer's disease, cardiac hypertrophy, left ventricular hypertrophy, hypertriglyceridemia, low HDL cholesterol, cardiovascular disorders such as coronary heart disease (CHD), cerebrovascular disease, stroke, peripheral vascular disease, sudden death, gallbladder diseases, cancer (breast, endometrial, colon), breathlessness, hyperuricemia, impaired fertility, low back pain, or increased anesthetic risk, and the like.

  本发明涉及一种式(I)的化合物：1（其中A、B、C和D独立地为氮或可选择性取代的亚甲基；E为氮、亚甲基或羟基取代的亚甲基；n为0或1；T、U、V和W独立地为氮或可选择性取代的亚甲基；X为—N（SO2R4）—、—N（COR5）—或—CO—；Y为—C（R6）（R7）—、—O—或—N（R8）—，但当E为氮、n为0、X为—CO—且Y为—O—时，化合物（I）被排除），以及类似物，它们可用作治疗与NPY相关的各种疾病的药剂，例如心血管疾病（如心绞痛、急性或充血性心力衰竭、心肌梗死、高血压、肾病、电解质异常、血管痉挛、动脉硬化等），中枢神经系统疾病（如暴食症、抑郁症、焦虑症、癫痫、痴呆、疼痛、酗酒、戒毒、昼夜节律紊乱、精神分裂症、记忆障碍、睡眠障碍、认知障碍等），代谢性疾病（如肥胖症、糖尿病、激素异常、高胆固醇血症、高脂血症、痛风、脂肪肝等），生殖或生殖系统疾病（如不孕症、早产、性功能障碍等），胃肠道疾病、呼吸系统疾病、炎症性疾病或青光眼等，例如动脉粥样硬化、性腺功能减退症、雄激素过多症、多囊卵巢综合症（Pickwickian综合症）、多毛症、胃肠动力障碍、肥胖相关胃食管反流、肥胖低通气综合症、睡眠呼吸暂停、炎症、血管系统全身性炎症、骨关节炎、胰岛素抵抗、支气管收缩、酒精偏好、代谢综合症、阿尔茨海默病、心脏肥厚、左心室肥厚、高三酰甘油血症、低高密度脂蛋白胆固醇、心血管疾病（如冠心病、脑血管疾病、中风、周围血管疾病、猝死）、胆囊疾病、癌症（乳腺、子宫内膜、结肠）、气喘、高尿酸血症、生育能力受损、腰痛或增加的麻醉风险等。
• NOVEL BENZIMIDAZOLE DERIVATIVES
  申请人：OTAKE NORIKAZU

  公开号：US20100048600A1

  公开（公告）日：2010-02-25

  The present invention relates to a compound of the formula (I): (wherein A, B , C and D are independently nitrogen or optionally substituted methine; E is nitrogen, methine or hydroxy substituted methine; n is 0 or 1; T, U, V and W are independently nitrogen or optionally substituted methine; X is —N(SO 2 R 4 )—, —N(COR 5 )— or —CO—; Y is —C(R 6 )(R 7 )—, —O— or —N(R 8 )—, provided that the compound (I) when E is nitrogen, n is 0, X is —CO—, and Y is —O— is excluded) and the like, which are useful as an agent for the treatment of various diseases related to NPY, for example cardiovascular disorders such as angina, acute or congestive heart failure, myocardial infarction, hypertension, nephropathy, electrolyte abnormality, vasospasm, arteriosclerosis, etc., central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal, circadian rhythm disorders, schizophrenia, memory impairment, sleep disorders, cognitive impairment, etc., metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia, gout, fatty liver, etc., genital or reproductive disorders such as infertility, preterm labor, sexual dysfunction, etc., gastro-intestinal disorders, respiratory disorder, inflammatory diseases or glaucoma, and the like, also for example, atherosclerosis, hypogonadism, hyperandrogenism, polycystic ovary syndrome (Pickwickian syndrome), hirsutism, gastro-intestinal motility disorder, obesity-related gastro-esophageal reflux, obesity hypoventilation, sleep apnea, inflammation, systemic inflammation of the vasculature, osteoarthritis, insulin resistance, bronchoconstriction, alcohol preference, metabolic syndrome, Alzheimer's disease, cardiac hypertrophy, left ventricular hypertrophy, hypertriglyceridemia, low HDL cholesterol, cardiovascular disorders such as coronary heart disease (CHD), cerebrovascular disease, stroke, peripheral vascular disease, sudden death, gallbladder diseases, cancer (breast, endometrial, colon), breathlessness, hyperuricemia, impaired fertility, low back pain, or increased anesthetic risk, and the like.

  本发明涉及一种式（I）的化合物：其中A、B、C和D独立地表示氮或可选取代的亚甲基；E表示氮、亚甲基或羟基取代的亚甲基；n为0或1；T、U、V和W独立地表示氮或可选取代的亚甲基；X为-N（SO2R4）-、-N（COR5）-或-CO-；Y为-C（R6）（R7）-、-O-或-N（R8）-，但当E为氮，n为0，X为-CO-，且Y为-O-时，化合物（I）被排除。此类化合物可用作治疗与NPY相关的各种疾病的药物，例如心血管疾病（如心绞痛、急性或充血性心力衰竭、心肌梗死、高血压、肾病、电解质异常、血管痉挛、动脉硬化等）、中枢神经系统疾病（如暴食症、抑郁症、焦虑症、癫痫、老年痴呆、疼痛、酗酒、戒毒、昼夜节律紊乱、精神分裂症、记忆障碍、睡眠障碍、认知障碍等）、代谢性疾病（如肥胖症、糖尿病、激素异常、高胆固醇血症、高脂血症、痛风、脂肪肝等）、生殖系统或生殖障碍（如不孕症、早产、性功能障碍等）、胃肠道疾病、呼吸系统疾病、炎症性疾病或青光眼等，例如动脉粥样硬化、性腺功能减退、高雄激素症、多囊卵巢综合征（匹克威克综合征）、多毛症、胃肠道运动障碍、肥胖相关胃食管反流、肥胖低通气综合征、睡眠呼吸暂停、炎症、血管系统全身性炎症、骨关节炎、胰岛素抵抗、支气管收缩、酒精偏好、代谢综合征、阿尔茨海默病、心脏肥大、左心室肥大、高三酰甘油血症、低高密度脂蛋白胆固醇、心血管疾病如冠心病、脑血管疾病、中风、外周血管疾病、猝死、胆囊疾病、癌症（乳腺、子宫内膜、结肠）、气短、高尿酸血症、生育能力受损、腰痛或麻醉风险增加等。
• THIAZOLO-PYRIDINE COMPOUNDS AS HIF MODULATORS
  申请人：Fibrogen, Inc.

  公开号：EP3124489A1

  公开（公告）日：2017-02-01

  The present invention relates to novel compounds of formula I wherein: q is 0 or 1; • A is -S- and B is =N-; or • A is =N- and B is -S-; one of -A≃C(R6)- or -B≃C(R6)- is a double bond and the other is a single bond; R1 is selected from the group consisting of hydroxyl, alkoxy, substituted alkoxy, acyloxy, cycloalkoxy, substituted cycloalkoxy, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, heterocyclyloxy, substituted heterocyclyloxy, mercapto, thioether, sustituted alkylthio, arylsulfanyl, heteroarylsulfanyl, amino, substituted amino, acylamino, and aminoacyl; R2is selected from the group consisting of hydrogen, deuterium, and methyl; R3 is selected from the group consisting of hydrogen, deuterium, alkyl, and substituted alkyl; R4 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl; and R5 and R6 are as defined in claim 1; capable of modulating the stability and/or activity of hypoxia inducible factor (HIF).

  本发明涉及式 I 的新型化合物 其中 q 是 0 或 1； - A 是-S-，B 是＝N-；或 - A 是 =N-，B 是 -S-； -A≃C(R6)-或-B≃C(R6)-中的一个是双键，另一个是单键； R1 选自由羟基、烷氧基、取代的烷氧基、酰氧基、环烷氧基、取代的环烷氧基、芳氧基、取代的芳氧基、杂芳氧基、取代的杂芳氧基、杂环氧基、取代的杂环氧基、巯基、硫醚、取代的烷硫基、芳硫基、杂芳硫基、氨基、取代的氨基、酰氨基和氨基酰基组成的组； R2 选自氢、氘和甲基组成的组； R3 选自氢、氘、烷基和取代烷基组成的组； R4 选自由氢、烷基和取代烷基组成的组；以及 R5 和 R6 如权利要求 1 所定义； 能调节缺氧诱导因子（HIF）的稳定性和/或活性。
• EP2016078B1
  申请人：——

  公开号：EP2016078B1

  公开（公告）日：2016-06-15