5-(4-carboxyphenyl)-5,6,7,8-tetrahydroimidazo<1,5-a>pyridine | 93178-73-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 5-(4-carboxyphenyl)-5,6,7,8-tetrahydroimidazo<1,5-a>pyridine
• 英文别名: 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzoic acid；5-(p-carboxyphenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine
• CAS: 93178-73-5
• 化学式: C₁₄H₁₄N₂O₂
• 分子量: 242.277
• InChiKey: KLIYHHIBTVVFPB-UHFFFAOYSA-N

物化性质

• 熔点：
  309-310 °C (decomp)
• 沸点：
  521.3±43.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	5-(4-carbamylphenyl)-5,6,7,8-tetrahydroimidazo<1,5-a>pyridine	102676-43-7	C14H15N3O	241.293
  法倔唑	fadrozole	102676-47-1	C14H13N3	223.277

反应信息

• 作为反应物：
  描述：

  5-(4-carboxyphenyl)-5,6,7,8-tetrahydroimidazo<1,5-a>pyridine 在 氯化亚砜 、 氨 、 三氯氧磷 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 30.5h， 生成 法倔唑
  参考文献：
  名称：

  Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease

  摘要：

  A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-a]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.

  DOI：

  10.1021/jm00106a038
• 作为产物：
  描述：

  2-<4-(ethoxycarbonyl)phenyl>pyridine N-oxide 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 氢气 、 硫酸二甲酯 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 甲苯 为溶剂， 90.0 ℃ 、275.79 kPa 条件下， 反应 64.0h， 生成 5-(4-carboxyphenyl)-5,6,7,8-tetrahydroimidazo<1,5-a>pyridine
  参考文献：
  名称：

  Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease

  摘要：

  A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-a]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.

  DOI：

  10.1021/jm00106a038

文献信息

• [EN] TREATING ESTROGEN-DEPENDENT DISEASES WITH (-)-FADROZOLE<br/>[FR] TRAITEMENT DE MALADIES PROVOQUEES PAR LES OESTROGENES AU MOYEN DE (-)-FADROZOLE
  申请人：SEPRACOR, INC.

  公开号：WO1995028156A1

  公开（公告）日：1995-10-26

  (EN) Methods and compositions are disclosed utilizing optically pure (-)-fadrozole for the treatment of estrogen-dependent breast cancer, gynecomastia, systemic lupus erythematosus and premature labor while substantially reducing the concomitant liability of adverse effects associated with the racemic mixture of fadrozole. (-)-Fadrozole is an inhibitor of aromatase and is therefore useful in the treatment of other conditions supported by estrogen or caused by elevated estrogen levels.(FR) L'invention concerne des procédés et des compositions utilisant (-)-fadrozole optiquement pur, afin de traiter le cancer du sein provoqué par les ÷strogènes, la gynécomastie, le lupus érythémateux aigu disséminé et le travail avant terme tout en limitant sensiblement l'apparition simultanée d'effets secondaires associés au mélange racémique de fadrozole. (-)-Fadrozole est un inhibiteur d'aromatase et présente, de ce fait, une efficacité dans le traitement d'autres états relatifs à la présence d'÷strogènes ou provoqués par des niveaux élevés d'÷strogènes.

  使用光学纯的(-)-fadrozole来治疗雌激素依赖性乳腺癌、男性乳腺发育异常、系统性红斑狼疮和早产，同时大幅减少与racemic混合物fadrozole相关的不良反应的方法和组合物被揭示出来。(-)-Fadrozole是一种芳香化酶抑制剂，因此在治疗其他与雌激素有关或由雌激素水平升高引起的疾病方面也很有用。
• Substituted imidazo[5-a]pyridine derviatives and other substituted
  申请人：Ciba-Geigy Corporation

  公开号：US05428160A1

  公开（公告）日：1995-06-27

  Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidised etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 -C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidised etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3, or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

  本发明涉及一种式子I的化合物：##STR1## 其中R.sub.1代表氢，低烷基，取代的低烷基，硝基，卤素，自由的，醚化或酯化的羟基，自由的，醚化，氧化醚化或酯化的巯基，未取代的，单取代或双取代的氨基，铵离子，自由的或功能修饰的磺酸基，自由的或功能修饰的甲酰基，C.sub.2-C.sub.20-酰基，氰基，自由的或功能修饰的羧基；R.sub.2代表氢，低烷基，取代的低烷基，卤素；自由的，醚化或酯化的羟基；自由的，醚化，氧化醚化或酯化的巯基；自由或功能修饰的羧基或酰基；其7,8-二氢衍生物；以及式I*的化合物：##STR2## 其中n表示0、1、2、3或4，而R.sub.1和R.sub.2如上述式I中所定义，并且它们的盐；例如作为芳香化酶抑制剂；含有这些化合物的制药组合物；这些化合物用于治疗响应于例如哺乳动物中的芳香化酶抑制的情况的用途；制备这些化合物的过程和中间体。
• Substituted imidazo[1,5-A]pyridine derivatives and other substituted
  申请人：Ciba-Geigy Corporation

  公开号：US04728645A1

  公开（公告）日：1988-03-01

  Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidized etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 -C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidized etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3 or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

  本发明揭示了式I的化合物：##STR1## 其中R.sub.1代表氢、低碳基、取代的低碳基、硝基、卤素、自由、醚化或酯化的羟基、自由、醚化、氧化醚化或酯化的巯基、未取代的、单取代或双取代的氨基、铵离子、自由或功能修饰的磺酸基、自由或功能修饰的甲酰基、C.sub.2-C.sub.20酰基、氰基、自由或功能修饰的羧基；R.sub.2代表氢、低碳基、取代的低碳基、卤素；自由、醚化或酯化的羟基；自由、醚化、氧化醚化或酯化的巯基；自由或功能修饰的羧基或酰基。其7,8-二氢衍生物；以及式I*的化合物：##STR2## 其中n表示0、1、2、3或4，R.sub.1和R.sub.2如上所述，以及其盐；例如作为芳香化酶抑制剂；含有这些化合物的制药组合物；使用这些化合物治疗对哺乳动物的芳香化酶抑制等反应性疾病的方法；制备这些化合物的过程和中间体。
• Substituted imidazo[1,5-A]pyridine derivatives as aromatase inhibitors
  申请人：Ciba-Geigy Corporation

  公开号：US04617307A1

  公开（公告）日：1986-10-14

  Compounds of the formula ##STR1## wherein R.sub.1 represents cyano, nitro or C.sub.1 -C.sub.4 -alkyl or the 7,8-dihydro derivative thereof or the 5,6,7,8 tetrahydro derivative of the formula ##STR2## wherein R.sub.1 is as defined under formula Ia and R.sub.2 is hydrogen, C.sub.1 -C.sub.4 -alkyl, halogen etherified or esterified hydroxy or mercapto, carboxy-C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxycarbonyl-C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkanoyl, to stereoisomers, mixtures of these stereoisomers and salts of these compounds are disclosed as well as their preparation, pharmaceutical compositions containing the same and the use thereof as inhibitors of aromatase activity.

  该化合物的公式为##STR1##其中R.sub.1代表氰基，硝基或C.sub.1-C.sub.4-烷基或其7,8-二氢衍生物或公式##STR2##的5,6,7,8-四氢衍生物，其中R.sub.1如公式Ia所定义，R.sub.2为氢，C.sub.1-C.sub.4-烷基，卤素醚化或酯化的羟基或巯基，羧基-C.sub.1-C.sub.4-烷基或C.sub.1-C.sub.4-烷氧羰基-C.sub.1-C.sub.4-烷基或C.sub.1-C.sub.4-酰基，包括立体异构体，这些立体异构体的混合物和这些化合物的盐，以及它们的制备，含有它们的制药组合物以及作为芳香化酶活性抑制剂的用途。
• Substituted imidazo[1,5-a]pyridine derivatives and other substituted
  申请人：Ciba-Geigy Corp.

  公开号：US04889861A1

  公开（公告）日：1989-12-26

  Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidized etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 --C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidized etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3 or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

  本发明涉及式I的化合物，其中R.sub.1代表氢、低烷基、取代的低烷基、硝基、卤素、自由、醚化或酯化羟基、自由、醚化、氧化醚化或酯化巯基、未取代的、单取代或双取代的氨基、铵离子、自由或功能修饰的磺酸基、自由或功能修饰的甲酰基、C.sub.2-C.sub.20酰基、氰基、自由或功能修饰的羧基；R.sub.2代表氢、低烷基、取代的低烷基、卤素；自由、醚化或酯化羟基；自由、醚化、氧化醚化或酯化巯基；自由或功能修饰的羧基或酰基；其7,8-二氢衍生物；以及式I*的化合物，其中n表示0、1、2、3或4，R.sub.1和R.sub.2在式I下定义，以及它们的盐；例如作为芳香化酶抑制剂；含有这些化合物的制药组合物；这些化合物用于治疗哺乳动物对芳香化酶抑制等条件的用途；以及制备这些化合物的过程和中间体。