5-甲氧基茚-1-羧酸 | 116854-10-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 5-甲氧基茚-1-羧酸
• 中文别名: 2,3-二氢-5-甲氧基-1H-茚-1-羧酸
• 英文名称: 5-methoxy-2,3-dihydro-1H-indene-1-carboxylic acid
• 英文别名: 2,3-dihydro-5-methoxy-1H-inden-1-carboxylic acid；5-methoxyindan-1-carboxylic acid
• CAS: 116854-10-5
• 化学式: C₁₁H₁₂O₃
• 分子量: 192.214
• InChiKey: KWQZTFAAOCBAHM-UHFFFAOYSA-N

物化性质

• 沸点：
  371.8±42.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2918990090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  5-甲氧基茚-1-羧酸 在 正丁基锂 、 草酰氯 、 lithium hydroxide monohydrate 、 硫酸 、 双氧水 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 33.5h， 生成 (1R)-5-methoxy-1-(4-methoxybenzyl)-2,3-dihydro-1H-indene-1-carboxylic acid
  参考文献：
  名称：

  1-苄基茚满衍生物作为雌激素受体β的选择性激动剂的合成与构效关系

  摘要：

  雌激素受体β（ERβ）选择性激动剂被认为是治疗表达ERβ的组织中雌激素缺乏症状的有前途的候选者，并且没有患乳腺癌的风险，并且已有多种化合物被报道为ERβ选择性激动剂。其中，6-6双环含环结构（例如，异黄酮植物雌激素）被视为isobutestrol的环化类似物之一5b中，建议包括5-6双环也可以用作选择性ERβ配体，其他环化的支架。在这项研究中，我们评估了1-（4-羟基苄基）茚满-5-醇7a的选择性ERβ激动活性，并研究了其衍生物的构效关系（SAR）。一些官能团改善了7a的性能; 在茚满1位上引入腈基导致对ERβ的更高选择性（12a），并且进一步优选用氟或甲基取代侧基苯环（12b，d和e）。随后的12a手性拆分确定R - 12a具有优于S - 12a的轮廓。这可与有希望的选择性ERβ激动剂之一二芳基丙腈（DPN）5c相提并论，这表明这种基于茚满的支架具有提供更好的ERβ激动剂探针的潜力。

  DOI：

  10.1016/j.bmc.2016.09.047
• 作为产物：
  描述：

  methyl 5-methoxy-2,3-dihydro-1H-indene-1-carboxylate 在 sodium hydroxide 作用下， 反应 2.0h， 生成 5-甲氧基茚-1-羧酸
  参考文献：
  名称：

  A Novel Method for the Synthesis of Methyl Indane-1-carboxylates by Ring Contraction of Tetralones Using Lead(IV) Acetate

  摘要：

  在三氟化硼醚化物和甲醇存在下，四氢萘酮与乙酸铅（IV）发生平滑的环收缩，从而得到茚-1-甲酸甲酯，产率令人满意。该方法可扩展到五元和七元环芳香酮。

  DOI：

  10.1055/s-1987-28099

文献信息

• Process for preparing a 2,3-dihydro-1H-imidazolyl-ethoxy indene
  申请人：Ferrer Internacional S.A.

  公开号：US04843165A1

  公开（公告）日：1989-06-27

  A process is disclosed for preparing a 2,3-dihydro-1H-imidazolylethoxy indene antithrombotic agent and its pharmaceutically acceptable salts.

  揭示了一种制备2,3-二氢-1H-咪唑乙氧基茚抗血栓药物及其药用盐的方法。
• Novel amide derivatives and medicinal use thereof ugs
  申请人：——

  公开号：US20040138223A1

  公开（公告）日：2004-07-15

  The present invention relates to an amide derivative of the formula (1), having a C5a receptor antagonistic action 1 wherein each symbol is as defined in the specification. The above-mentioned amide derivative, an optically active form thereof and a pharmaceutically acceptable salt thereof are promising as an agent for the treatment or prophylaxis of diseases or syndromes caused by inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia reperfusion, trauma, burn, surgical invasion and the like]. Moreover, they are useful as a therapeutic or prophylactic agent for the infectious diseases caused by bacteria and virus that invade via a C5a receptor.

  本发明涉及一种式（1）的酰胺衍生物，具有C5a受体拮抗作用，其中每个符号如规范中所定义。上述酰胺衍生物及其光学活性形式和药学上可接受的盐被认为是治疗或预防因C5a引起的炎症引起的疾病或综合症的药物，如自身免疫性疾病，如风湿病，系统性红斑狼疮等，败血症，成人呼吸窘迫综合症，慢性阻塞性肺疾病，哮喘等过敏性疾病，动脉粥样硬化，心脏梗死，脑梗死，牛皮癣，老年痴呆症和严重器官损伤（如肺炎，肾炎，肝炎，胰腺炎等）由于缺血再灌注，创伤，烧伤，手术入侵等引起的白细胞激活。此外，它们对通过C5a受体侵入的细菌和病毒引起的传染病也有用作治疗或预防剂。
• Novel amide derivatives and medicinal use thereof
  申请人：NAKAMURA Mitsubaru

  公开号：US20100041656A1

  公开（公告）日：2010-02-18

  The present invention relates to an amide derivative of the formula (1), having a C5a receptor antagonistic action wherein each symbol is as defined in the specification. The above-mentioned amide derivative, an optically active form thereof and a pharmaceutically acceptable salt thereof are promising as an agent for the treatment or prophylaxis of diseases or syndromes caused by inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia reperfusion, trauma, burn, surgical invasion and the like]. Moreover, they are useful as a therapeutic or prophylactic agent for the infectious diseases caused by bacteria and virus that invade via a C5a receptor.

  本发明涉及一种式（1）的酰胺衍生物，具有C5a受体拮抗作用，其中每个符号如规范中所定义。上述酰胺衍生物及其光学活性形式和药学上可接受的盐被认为是治疗或预防由C5a引起的炎症所致疾病或综合症的药物，例如自身免疫性疾病，如风湿病，系统性红斑狼疮等，败血症，成人呼吸窘迫综合症，慢性阻塞性肺疾病，过敏性疾病，如哮喘等，动脉硬化，心脏梗塞，脑梗塞，牛皮癣，阿尔茨海默病和严重器官损伤（例如，肺炎，肾炎，肝炎，胰腺炎等），由缺血再灌注，创伤，烧伤，手术侵袭等引起的白细胞激活所致。此外，它们还可用作通过C5a受体侵入的细菌和病毒引起的传染病的治疗或预防剂。
• Amide derivatives and medicinal use thereof
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：US07855297B2

  公开（公告）日：2010-12-21

  The present invention relates to an amide derivative of the formula (1), having a C5a receptor antagonistic action wherein each symbol is as defined in the specification. The above-mentioned amide derivative, an optically active form thereof and a pharmaceutically acceptable salt thereof are promising as an agent for the treatment or prophylaxis of diseases or syndromes caused by inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia reperfusion, trauma, burn, surgical invasion and the like]. Moreover, they are useful as a therapeutic or prophylactic agent for the infectious diseases caused by bacteria and virus that invade via a C5a receptor.

  本发明涉及一种具有C5a受体拮抗作用的公式（1）的酰胺衍生物，其中每个符号如规范中所定义。上述酰胺衍生物及其光学活性形式和药学上可接受的盐作为治疗或预防由C5a引起的炎症引起的疾病或综合征的药物很有前途[例如，自身免疫疾病，如风湿病，系统性红斑狼疮等，败血症，成人呼吸窘迫综合症，慢性阻塞性肺疾病，过敏疾病，如哮喘等，动脉硬化，心肌梗死，脑梗死，牛皮癣，阿尔茨海默病和严重器官损伤（例如，由缺血再灌注，创伤，烧伤，手术入侵等引起的白细胞激活引起的肺炎，肾炎，肝炎和胰腺炎等）]。此外，它们也可用作通过C5a受体侵入的细菌和病毒引起的传染病的治疗或预防药物。
• Process for preparing 2,3-dihydro-1H-imidazolylalkoxyindene derivatives and pharmaceutically acceptable salts, and intermediate therefor
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：EP0275104A2

  公开（公告）日：1988-07-20

  The invention relates to a process for preparing 2,3-dihydro-1H-imidazolylalkoxyindene derivatives and its pharmaceutically acceptable salts, characterized in that 5-methoxy-l-indanone is used as a starting compound, followed by formation of the corresponding cyanohydrine, treatment with stannous chloride to give 2,3-dihydro-5-methoxy-1H-indene-i-carboxylic acid, followed by subsequent demethylation of the methoxy group, protection of the carboxylic acid group by esterification, formation of the corresponding ω-chloroalkyl ether, reaction with imidazole and final hydrolysis, thus obtaining 2,3-dihydro-5-[β-(1H-imidazol-1-yl)-alkoxy]-1H-indene-1-carboxylic acid. The process gives the intermediates in high purity and high yields so that the intermediates can be further processed without purification which results in an elevated overall yield.

  本发明涉及一种制备 2,3-二氢-1H-咪唑烷氧基茚衍生物及其药学上可接受的盐类的工艺，其特征在于使用 5-甲氧基-l-茚酮作为起始化合物，然后形成相应的氰基水合物，用氯化亚锡处理得到 2、3-二氢-5-甲氧基-1H-茚-i-羧酸，然后将甲氧基去甲基化，通过酯化作用保护羧酸基团，形成相应的ω-氯烷基醚，与咪唑反应，最后水解，从而得到 2,3-二氢-5-[β-（1H-咪唑-1-基）-烷氧基]-1H-茚-1-羧酸。该工艺可获得高纯度和高产率的中间体，因此中间体无需纯化即可进一步加工，从而提高了总产率。