trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid
• 英文别名: trans-3'-oxospiro[cyclohexane-1,1'(3'H)-isobenzofuran]-4-carboxylic acid；trans-3'-Oxo-spiro[cyclohexane-1,1'(3'H)-isobenzofuran]-4-carboxylic acid；3-oxospiro[2-benzofuran-1,4'-cyclohexane]-1'-carboxylic acid
• 化学式: C₁₄H₁₄O₄
• 分子量: 246.263
• InChiKey: CDDYQAWKPYEZMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid 在 盐酸 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 、 乙酸乙酯 为溶剂， 反应 2.5h， 生成 trans-piperazinyl-3'-oxo-spiro[cyclohexane-1,1'-(3'H)-isobenzofuran]-4-carboxamide hydrochloride
  参考文献：
  名称：

  CARBAMOYL-SUBSTITUTED SPIRO DERIVATIVE

  摘要：

  公开号：

  EP1795527B1
• 作为产物：
  描述：

  4-hydroxymethylspiro[cyclohexane-1,1'(3'H)-isobenzofuran]-3'-one 在 三氯化钌 sodium periodate 、 盐酸 作用下， 以 氯仿 、 乙腈 、 水 为溶剂， 反应 1.0h， 生成 trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carboxylic acid
  参考文献：
  名称：

  Spiro compounds

  摘要：

  通式（I）的螺环化合物：其中Ar1代表可选择取代的芳基或杂环芳基；n代表0或1；T、U、V和W分别代表氮原子或可选择取代的甲基基团，其中至少两个代表所述的甲基基团；X代表甲基；Y代表可选择取代的亚胺基或氧原子。这些新型螺环化合物表现出神经肽Y受体（NPY）拮抗活性，并可用作治疗与NPY相关的各种疾病的药物，例如心血管疾病、中枢神经系统疾病、代谢性疾病等。

  公开号：

  US06335345B1

文献信息

• Novel azole derivatives
  申请人：Otake Norikazu

  公开号：US20060111380A1

  公开（公告）日：2006-05-25

  The present invention relates to a compound of the formula (I): wherein Az is a group comprising a monocyclic azole or a bicyclic aromatic ring of the same or different fused azoles; T, U, V and W are independently methine or nitrogen, said methine being optionally substituted by a substituent, and at least two of T, U, V and W are said methine groups; and X is nitrogen or methine. The compounds of the present invention are useful as agents for the treatment of various kinds of diseases related to NPY, for example, cardiovascular disorders, nervous system disorders, genitative diseases, metabolic diseases, genital or reproductive disorders, gastrointestinal disorders, respiratory disorders, inflammatory diseases or glaucoma, and the like.

  本发明涉及一种式子为(I)的化合物：其中，Az是包含单环唑或同种或不同融合唑的双环芳香环的基团；T、U、V和W独立地是亚甲基或氮，所述亚甲基可以选用取代基进行取代，且至少有两个T、U、V和W是所述亚甲基基团；而X是氮或亚甲基。本发明的化合物可用作治疗与NPY相关的各种疾病的药剂，例如心血管疾病、神经系统疾病、遗传性疾病、代谢性疾病、生殖器或生殖系统疾病、胃肠疾病、呼吸系统疾病、炎症性疾病或青光眼等。
• Novel spiro compounds
  申请人：——

  公开号：US20030220499A1

  公开（公告）日：2003-11-27

  Compounds of the general formula (I): 1 (wherein Ar 1 represents optionally substituted aryl or heteroaryl; n represents 0 or 1; T, U, V and W represent independently nitrogen atom or optionally substituted methine group, where at least two of them represent the said methine group; X represents methine or nitrogen; Y represents optionally substituted imino or oxygen atom) exhibit NPY antagonistic activities and are useful as agents for the treatment of various diseases related to NPY, for example, cardiovascular disorders such as hypertension, nephropathy, heart disease, vasospasm, arteriosclerosis and the like, central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal and the like, metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia and the like, sexual and reproductive dysfunction, gastrointestinal disorder, respiratory disorder, inflammation or glaucoma, and the like.

  通式（I）的化合物：1（其中Ar1代表可选取代的芳基或杂环芳基；n代表0或1；T、U、V和W分别独立地代表氮原子或可选取代的甲烷基，其中至少两个代表所述的甲烷基；X代表甲烷或氮；Y代表可选取代的亚胺基或氧原子）表现出NPY拮抗活性，并且可用作治疗与NPY相关的各种疾病的药物，例如心血管疾病如高血压、肾病、心脏病、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、药物戒断等，代谢性疾病如肥胖症、糖尿病、激素异常、高胆固醇血症、高脂血症等，性和生殖功能障碍、胃肠道疾病、呼吸系统疾病、炎症或青光眼等。
• NOVEL SPIRO COMPOUNDS
  申请人：——

  公开号：US20020052371A1

  公开（公告）日：2002-05-02

  Compounds of the general formula (I): 1 (wherein Ar 1 represents optionally substituted aryl or heteroaryl; n represents 0 or 1; T, U, V and W represent independently nitrogen atom or optionally substituted methine group, where at least two of them represent the said methine group; X represents methine or nitrogen; Y represents optionally substituted imino or oxygen atom) exhibit NPY antagonistic activities and are useful as agents for the treatment of various diseases related to NPY, for example, cardiovascular disorders such as hypertension, nephropathy, heart disease, vasospasm, arteriosclerosis and the like, central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal and the like, metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia and the like, sexual and reproductive dysfunction, gastro-intestinal disorder, respiratory disorder, inflammation or glaucoma, and the like.

  通式（I）化合物（其中Ar1代表可选取代的芳基或杂环芳基；n代表0或1；T、U、V和W独立地代表氮原子或可选取代的甲基基团，其中至少有两个代表所述甲基基团；X代表甲基或氮原子；Y代表可选取代的亚胺基或氧原子）表现出NPY拮抗活性，并且可用作治疗与NPY相关的各种疾病的药剂，例如心血管疾病，如高血压、肾病、心脏病、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、戒断等，代谢性疾病，如肥胖症、糖尿病、激素异常、高胆固醇血症、高脂血症等，性和生殖功能障碍、胃肠道疾病、呼吸系统疾病、炎症或青光眼等。
• Novel benzimidazole derivatives
  申请人：Otake Norikazu

  公开号：US20060205750A1

  公开（公告）日：2006-09-14

  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分别独立表示氮或可选取代的甲烷基；E表示氮、甲烷基或羟基取代的甲烷基；n为0或1；T、U、V和W分别独立表示氮或可选取代的甲烷基；X为—N（SO2R4）—、—N（COR5）—或—CO—；Y为—C（R6）（R7）—、—O—或—N（R8）—，但当化合物（I）中E为氮，n为0，X为—CO—，Y为—O—时，该化合物被排除在外。此外，该化合物及其类似物可用作治疗与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贪食症、抑郁症、焦虑症、癫痫、痴呆、疼痛、酗酒、戒断症状、生物钟紊乱、精神分裂症、记忆力减退、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、高雄激素血症、多囊卵巢综合症（皮克威克综合症）、多毛症、胃肠道运动障碍、肥胖相关的胃食管反流、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、周围血管疾病、猝死、胆囊疾病、癌症（乳腺、子宫内膜、结肠）、呼吸困难、高尿酸血症、生育能力下降、腰痛或麻醉风险增加等。
• Carbamoyl-Substituted Spiro Derivative
  申请人：Jitsuoka Makoto

  公开号：US20080171753A1

  公开（公告）日：2008-07-17

  A compound represented by, e.g. the formula (I): [wherein X, Y, Z, and W each independently represent optionally substituted methine; A, B, and D each independently represent —C(O)—, etc.; Q represents a methine or a nitrogen; and R represents the formula (II-1), optionally substituted with lower alkyl, etc.; (wherein R 6 represents a lower alkyl, etc; and R 7 and R 8 each independently represents a lower alkyl, etc.)] or a pharmaceutically acceptable salt of the compound. The compounds and salt have antagonistic activity against a histamine H3 receptor or inverse agonistic activity against a histamine H3 receptor. They are useful in the prevention or treatment of metabolic diseases, circulatory diseases, or neurotic diseases.

  化合物的化学式为(I):[其中X、Y、Z和W各自独立地表示可选择性取代的甲烷基；A、B和D各自独立地表示—C(O)—等；Q表示甲烷基或氮；R表示化学式(II-1)，可选择性地取代较低的烷基等；(其中R6表示较低的烷基等；R7和R8各自独立地表示较低的烷基等)]或其药学上可接受的盐。这些化合物和盐对组胺H3受体具有拮抗活性或反向激动活性。它们可用于预防或治疗代谢性疾病、循环系统疾病或神经疾病。