1,4-methano-1,2,3,4-tetrahydro-6-naphthalenecarboxylic acid | 91587-22-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1,4-methano-1,2,3,4-tetrahydro-6-naphthalenecarboxylic acid
• 英文别名: Tricyclo[6.2.1.02,7]undeca-2(7),3,5-triene-4-carboxylic acid；tricyclo[6.2.1.02,7]undeca-2(7),3,5-triene-4-carboxylic acid
• CAS: 91587-22-3
• 化学式: C₁₂H₁₂O₂
• 分子量: 188.226
• InChiKey: CYVBQJNJHBYVJW-UHFFFAOYSA-N

物化性质

• 沸点：
  338.1±31.0 °C(Predicted)
• 密度：
  1.275±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,4-methano-1,2,3,4-tetrahydro-6-naphthalenecarboxylic acid 在 吡啶 、 chromium(VI) oxide 、 lithium aluminium tetrahydride 、 正丁基锂 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.33h， 生成 6-ethenyl-1,4-methano-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  Conformationally restricted retinoids

  摘要：

  A series of conformationally restricted retinoids was synthesized and screened in two assays used to measure the ability of retinoids to control cell differentiation, namely, the reversal of keratinization in tracheal organ culture from vitamin A deficient hamsters and the inhibition of the induction of mouse epidermal ornithine decarboxylase by a tumor promoter. These compounds had bonds corresponding to selected bonds of the E-tetraene chain of retinoic acid (1) held in a planar cisoid conformation by inclusion in an aromatic ring. The meta-substituted analogue 3 of 4-[(E)-2-methyl-4-(2,6,6-trimethylcyclohexenyl)-1,3-butadienyl+ ++]benzoic acid (2) was far less active than 2 in both assays. In contrast, the vinyl homologue of 2 (4) and the 7,8-dihydro and 7,8-methano analogues (5 and 6) had activity comparable to that of 2. Analogues of 4-[(E)-2-(1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-6-naphthyl)propenyl] benzoic acid (7) were also screened. Replacement of the tetrahydronaphthalene ring of 7 by a benzonorbornenyl group (9) significantly reduced activity, as did removal of the vinylic methyl group from 9 (10). Replacement of the propenyl group of 9 by a cyclopropane ring (12) also reduced activity. Replacement of the tetrahydronaphthalene ring of 7 by 4,4-dimethyl-3,4-dihydro-2H-1-benzopyran and -benzothiopyran rings (13 and 14) also decreased activity. Inclusion of the 7,9 double bond system of 1 in an aromatic ring (15 and 16) reduced activity, whereas inclusion of the 5,7 double bond system in an aromatic ring enhanced activity (7 and 19). Inclusion of the 11,13 and 9,11,13 double bond systems in aromatic rings (2 and 18) also reduced activity below that of 1. Retinoic acid, 7, 13, 14, and 19 inhibited papilloma tumor formation in mice. Toxicity testing indicated that 7 was more toxic than 1, 13, 14, and 19, 19 was more toxic than 1, and 13 and 14 were less toxic than 1.

  DOI：

  10.1021/jm00377a022
• 作为产物：
  描述：

  三环[6.2.1.02,7]十一碳-2,4,6-三烯 在 三氯化铝 、 sodium hypobromide 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 反应 1.5h， 生成 1,4-methano-1,2,3,4-tetrahydro-6-naphthalenecarboxylic acid
  参考文献：
  名称：

  Conformationally restricted retinoids

  摘要：

  A series of conformationally restricted retinoids was synthesized and screened in two assays used to measure the ability of retinoids to control cell differentiation, namely, the reversal of keratinization in tracheal organ culture from vitamin A deficient hamsters and the inhibition of the induction of mouse epidermal ornithine decarboxylase by a tumor promoter. These compounds had bonds corresponding to selected bonds of the E-tetraene chain of retinoic acid (1) held in a planar cisoid conformation by inclusion in an aromatic ring. The meta-substituted analogue 3 of 4-[(E)-2-methyl-4-(2,6,6-trimethylcyclohexenyl)-1,3-butadienyl+ ++]benzoic acid (2) was far less active than 2 in both assays. In contrast, the vinyl homologue of 2 (4) and the 7,8-dihydro and 7,8-methano analogues (5 and 6) had activity comparable to that of 2. Analogues of 4-[(E)-2-(1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-6-naphthyl)propenyl] benzoic acid (7) were also screened. Replacement of the tetrahydronaphthalene ring of 7 by a benzonorbornenyl group (9) significantly reduced activity, as did removal of the vinylic methyl group from 9 (10). Replacement of the propenyl group of 9 by a cyclopropane ring (12) also reduced activity. Replacement of the tetrahydronaphthalene ring of 7 by 4,4-dimethyl-3,4-dihydro-2H-1-benzopyran and -benzothiopyran rings (13 and 14) also decreased activity. Inclusion of the 7,9 double bond system of 1 in an aromatic ring (15 and 16) reduced activity, whereas inclusion of the 5,7 double bond system in an aromatic ring enhanced activity (7 and 19). Inclusion of the 11,13 and 9,11,13 double bond systems in aromatic rings (2 and 18) also reduced activity below that of 1. Retinoic acid, 7, 13, 14, and 19 inhibited papilloma tumor formation in mice. Toxicity testing indicated that 7 was more toxic than 1, 13, 14, and 19, 19 was more toxic than 1, and 13 and 14 were less toxic than 1.

  DOI：

  10.1021/jm00377a022

文献信息

• [EN] SUBSTITUTED AMIDES, METHOD OF MAKING, AND USE AS BTK INHIBITORS<br/>[FR] AMIDES SUBSTITUÉS, LEUR MÉTHODE DE PRÉPARATION ET D'UTILISATION EN TANT QU'INHIBITEURS DE BTK
  申请人：CGI PHARMACEUTICALS INC

  公开号：WO2009137596A1

  公开（公告）日：2009-11-12

  Compounds of Formula I that inhibit Btk are described herein. Pharmaceutical compositions comprising at least one compound of Formula I, together with at least one pharmaceutically acceptable vehicle chosen from carriers, adjuvants, and excipients. are described. Methods of treating patients suffering from certain diseases responsive to inhibition of Btk activity and/ or B-cell activity are described. Methods for determining the presence of Btk in a sample are described.

  本文描述了化学式I的化合物，其抑制Btk。还描述了包含至少一种化学式I化合物的制药组合物，以及至少选择自载体、佐剂和赋形剂中的一种药用可接受载体。本文还描述了治疗对抑制Btk活性和/或B细胞活性敏感的某些疾病的患者的方法。本文还描述了用于确定样品中Btk存在的方法。
• BENZONORBORNENYL, BENZOPYRANYL AND BENZOTHIOPYRANYL RETINOIC ACID ANALOGUES
  申请人：SRI INTERNATIONAL

  公开号：EP0155940A1

  公开（公告）日：1985-10-02
• SUBSTITUTED AMIDES, METHOD OF MAKING, AND USE AS BTK INHIBITORS
  申请人：CGI Pharmaceuticals, Inc.

  公开号：EP2297105A1

  公开（公告）日：2011-03-23
• [EN] BENZONORBORNENYL, BENZOPYRANYL AND BENZOTHIOPYRANYL RETINOIC ACID ANALOGUES
  申请人：SRI INTERNATIONAL

  公开号：WO1985000806A1

  公开（公告）日：1985-02-28

  (EN) Compounds of the formulas (I), (II) and (III), where R1, R2, R3 and R4 are hydrogen or methyl, X is hydrogen or fluorine and Q is formula (IV), (V), (VI), (VII), (VIII), or (IX), and X1 is hydrogen, hydroxy, methoxy or fluorine, R is hydroxy, alkoxy with 0 or 1 hydroxy substituent, aroxy or NR5R6, where R5 is hydrogen, alkyl with 0 or 1 hydroxy substituent or aryl, and R6 is alkyl with 0 or 1 hydroxy substituent or aryl, with the provisos that X is fluorine only when R2 is methyl, when R3 or R4 is methyl the other R3 or R4 is also methyl and when Q is said thienyl group Q may be in either the cis or trans position. These compounds are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders. (FR) Composés de formules (I), (II) et (III), où R1, R2, R3 et R4 représentent un hydrogène ou un méthyle, X représente un hydrogène ou un fluor et Q représente (IV), (V), (VI), (VII), (VIII) ou (IX) et X1 représente un hydrogène, un hydroxy, un méthoxy ou un fluor, R représente un hydroxy, un alkoxy avec 0 ou 1 substituant hydroxy, un aroxy ou NR5R6, où R5 représente un hydrogène, un alcoyle avec 0 ou 1 substituant hydroxy ou un aryle, et R6 représente un alcoyle avec 0 ou 1 substituant hydroxy ou un aryle, à condition que X ne représente un fluor que lorsque R2 est un méthyle, lorsque R3 ou R4 est un méthyle, l'autre R3 ou R4 étant également un méthyle et lorsque Q est un groupe thiényle, Q pouvant être en position cis ou trans. Ces composés sont utiles comme agents chimiopréventifs pour inhiber l'activation tumorale dans des cellules épithéliales et pour traiter des affections cutanées non malignes.
• [EN] AMIDINE COMPOUND OR SALT THEREOF<br/>[FR] COMPOSÉ AMIDINE OU SEL ASSOCIÉ
  申请人：TOYAMA CHEMICAL CO LTD

  公开号：WO2015025962A1

  公开（公告）日：2015-02-26

  一般式 「式中、Ｒ１およびＲ２は、Ｃ１－６アルキル基などを;Ｒ３は、水素原子などを；Ｒ４Ａは、置換されていてもよいアリール基または置換されていてもよい複素環式基などを；Ｒ５およびＲ６は、Ｃ１－６アルキル基などを；Ｘ１は、メチレン基などを；Ｚ１およびＺ２は、ＣＨなどを示す。」で表される化合物またはその塩は、抗真菌剤として有用である。