3-(1H-imidazol-1-ylmethyl)-2H-1-benzopyran-6-carboxylic acid | 129498-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3-(1H-imidazol-1-ylmethyl)-2H-1-benzopyran-6-carboxylic acid
• 英文别名: 2H-1-Benzopyran-6-carboxylic acid, 3-(1H-imidazol-1-ylmethyl)-；3-(imidazol-1-ylmethyl)-2H-chromene-6-carboxylic acid
• CAS: 129498-34-6
• 化学式: C₁₄H₁₂N₂O₃
• 分子量: 256.261
• InChiKey: GGCTZXGFWKXKFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-dihydro-3(1H-imidazol-1-ylmethyl)-4-hydroxy-2H-1-benzopyran-6-carboxylic acid 在 硫酸 作用下， 以 溶剂黄146 为溶剂， 反应 4.0h， 以60%的产率得到3-(1H-imidazol-1-ylmethyl)-2H-1-benzopyran-6-carboxylic acid
  参考文献：
  名称：

  N-imidazolyl derivatives of the napththalene and chroman rings as thromboxane A2 synthase inhibitors

  摘要：

  A series of N-imidazol-1-yl derivatives of 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthalene, 2H-1-benzopyran and some related compounds were synthesized and tested as inhibitors of thromboxane A2 synthase in ex vivo experiments with orally treated rats. Some compounds showed good activity which was confirmed in experiments in vitro in rabbit whole blood. Some structural requirements for significant TxA2 synthase inhibitory activity are discussed. The selected 5,6-Dihydro-7-(H-1-imidazol-1-yl)-2-naphthalene-carboxylic acid (compound 7) was conformationally analysed using the Sybyl molecular model system in comparison with dazoxiben. Compound 7 was further pharmacologically investigated and on the basis of its interesting activities in vitro, ex vivo and in vivo and its low toxicity was selected for clinical investigation.

  DOI：

  10.1016/0223-5234(91)90103-t

文献信息

• N-imidazolyl- and N-imidazolylmethyl-derivatives of substituted bicyclic
  申请人：Farmitalia Carlo Erba, S.r.l.

  公开号：US05204364A1

  公开（公告）日：1993-04-20

  The present invention relates to new N-imidazolyl and N-imidazolylmethyl derivatives of bicyclic compounds having the general formula (I) ##STR1## Wherein A is a .gtoreq.CR.sub.3 or >CHR.sub.3 group, in which R.sub.3 is hydrogen or C.sub.1 -C.sub.6 alkyl, or a >C.dbd.CR.sub.4 R.sub.5 group, in which each of R.sub.4 and R.sub.5 independently is hydrogen or C.sub.1 -C.sub.5 alkyl; Z is --CH.sub.2 --, --O-- or --S--; n is zero or 1; each of R and R.sub.1 is independently hydrogen or C.sub.1 -C.sub.6 alkyl; R.sub.2 is --COCH.sub.2 OH, --CH.sub.2 OR', --COOR', --CONR'R" or --CH.dbd.CH--COOR', in which each of R' and R" independently is hydrogen or C.sub.1 -C.sub.6 alkyl, and the pharmaceutically acceptable salts thereof; and wherein: a) when n is zero, then Z is --CH.sub.2 -- or --O--; whereas when n is one, then Z is --CH.sub.2 --, --O-- or --S--; b) when A is .gtoreq.CR.sub.3 or >CHR.sub.3 in which R.sub.3 is hydrogen, then n is one; and c) when, at the same time, A is >CHR.sub.3 in which R.sub.3 is hydrogen, Z is --CH.sub.2 --, n is one and R.sub.2 is --COOR' wherein R' is as defined above, then at least one of R and R.sub.1 is other than hydrogen, which are useful in the treatment of diseases related to an enhancement of TxA.sub.2 synthesis.

  本发明涉及具有通式（I）的新的N-咪唑基和N-咪唑基甲基衍生物的双环化合物： 其中A是.gtoreq.CR.sub.3或>CHR.sub.3基团，其中R.sub.3是氢或C.sub.1 -C.sub.6烷基，或>C.dbd.CR.sub.4R.sub.5基团，其中R.sub.4和R.sub.5各自独立地是氢或C.sub.1 -C.sub.5烷基；Z是--CH.sub.2--，--O--或--S--；n为零或1；R和R.sub.1各自独立地是氢或C.sub.1 -C.sub.6烷基；R.sub.2是--COCH.sub.2OH，--CH.sub.2OR'，--COOR'，--CONR'R"或--CH.dbd.CH--COOR'，其中R'和R"各自独立地是氢或C.sub.1 -C.sub.6烷基，以及其药学上可接受的盐；在以下情况下：a）当n为零时，Z为--CH.sub.2--或--O--；而当n为一时，Z为--CH.sub.2--，--O--或--S--；b）当A为.gtoreq.CR.sub.3或>CHR.sub.3且R.sub.3为氢时，n为一；和c）当同时A为>CHR.sub.3且R.sub.3为氢，Z为--CH.sub.2--，n为一且R.sub.2为--COOR'，其中R'如上定义时，至少有一个R和R.sub.1不是氢，这些衍生物在治疗与TxA.sub.2合成增强相关的疾病方面是有用的。
• N-imidazolyl-and N-imidazolyl-methyl derivatives or substituted bicyclic compounds
  申请人：FARMITALIA CARLO ERBA S.r.l.

  公开号：EP0363789A1

  公开（公告）日：1990-04-18

  The present invention relates to new N-imidazolyl and N-imidazolylmethyl derivatives of bicyclic compounds having the general formula (I) Wherein A is a OR3 or CHR3 group, in which R3 is hydrogen or C1-C6 alkyl, or a C=CR4R5 group, in which each of R4 and Rs independently is hydrogen or C1-C5 alkyl; Z is -CH2-, -O- or -S-; n is zero or 1; each of R and R1 is independently hydrogen or C1-C6 alkyl; R2 is -COCH20H, -CH20R', -COOR', -CONR'R" or -CH=CH-COOR', in which each of R' and R" independently is hydrogen or C1-C6 alkyl, and the pharmaceutically acceptable salts thereof; and wherein: a) when n is zero, then Z is -CH2- or -O-; whereas when n is one, then Z is -CH2-, -O- or -S-; b) when A is CR3 or CHR3 in which R3 is hydrogen, then n is one; and c) when at the same time,A is CHR3 in which R3 is hydrogen, Z is -CH2-, n is one and R2 is -COOR wherein R is as defined above, then at least one of R and R1 is other than hydrogen. which are useful in the treatment of diseases related to an enhancement of TxA2 synthesis.

  本发明涉及具有通式(I)的双环化合物的新 N-咪唑基和 N-咪唑基甲基衍生物 其中 A是OR3或CHR3基团，其中R3是氢或C1-C6烷基，或C＝CR4R5基团，其中R4和Rs各自独立地是氢或C1-C5烷基； Z 是-CH2-、-O-或-S-； n 为零或 1； R 和 R1 各自独立地为氢或 C1-C6 烷基； R2 是-COCH20H、-CH20R'、-COOR'、-CONR'R "或-CH=CH-COOR'，其中 R' 和 R "各自独立地是氢或 C1-C6 烷基，以及它们的药学上可接受的盐；其中： a) 当 n 为零时，则 Z 为-CH2-或-O-；而当 n 为 1 时，则 Z 为-CH2-、-O-或-S-； b) 当 A 为 CR3 或 CHR3（其中 R3 为氢）时，n 为 1；以及 c) 同时，当 A 是 CHR3（其中 R3 是氢）、Z 是-CH2-、n 是 1 且 R2 是-COOR（其中 R 如上文所定义）时，则 R 和 R1 中至少有一个不是氢。 这些物质可用于治疗与 TxA2 合成增强有关的疾病。
• N-IMIDAZOLYL- AND N-IMIDAZOLYLMETHYL-DERIVATIVES OF SUBSTITUTED BICYCLIC COMPOUNDS
  申请人：FARMITALIA CARLO ERBA S.r.l.

  公开号：EP0389613A1

  公开（公告）日：1990-10-03
• US5204364A
  申请人：——

  公开号：US5204364A

  公开（公告）日：1993-04-20
• [EN] N-IMIDAZOLYL- AND N-IMIDAZOLYLMETHYL-DERIVATIVES OF SUBSTITUTED BICYCLIC COMPOUNDS
  申请人：FARMITALIA CARLO ERBA S.R.L.

  公开号：WO1990003970A1

  公开（公告）日：1990-04-19

  (EN) The present invention relates to new N-imidazolyl and N-imidazolylmethyl derivatives of bicyclic compounds having general formula (I), wherein A is an $g(a) or $g(b) group, in which R3 is hydrogen or C1-C6 alkyl, or a $g(c) group, in which each of R4 and R5 independently is hydrogen or C1-C5 alkyl; Z is -CH2-, -O- or -S-; n is zero or 1; each of R and R1 is independently hydrogen or C1-C6 alkyl; R2 is -COCH2OH, -CH2OR', -COOR', -CONR'R'' or -CH=CH-COOR', in which each of R' and R'' independently is hydrogen or C1-C6 alkyl, and the pharmaceutically acceptable salts thereof; and wherein: a) when n is zero, then Z is -CH2- or -O-; whereas when n is one, then Z is -CH2-, -O- or -S-; b) when A is $g(a) or $g(b) in which R3 is hydrogen, then n is one; and c) when, at the same time, A is $g(b) in which R3 is hydrogen, Z is -CH2-, n is one and R2 is -COOR' wherein R' is as defined above, then at least one of R and R1 is other than hydrogen, which are useful in the treatment of diseases related to an enhancement of TxA2 synthesis.(FR) La présente invention se rapporte à de nouveaux dérivés N-imidazolyle et N-imidazolylméthyle de composés bicycliques, qui sont représentés par la formule générale (I); où A représente un groupe $g(a) ou $g(b), R3 représentant l'hydrogène ou un alkyle C1-C5, ou un groupe $g(c), où chacun des éléments R4 et R5 représentent séparément l'hydrogène ou un alkyle C1-C5; Z représente -CH2-, -O- ou -S-; n est égal à zéro ou à 1; chacun des éléments R et R1 représente séparément l'hydrogène ou un alkyle C1-C6; R2 représente -COCH2OH, -CH2OR', -COOR', -CONR'R''; ou -CH=CH-COOR', où chacun des éléments R' et R'' représente séparément l'hydrogène ou un alkyle C1-C6; ainsi qu'aux sels pharmaceutiquement acceptables desdits dérivés. Dans ces dérivés: a) lorsque n est égal à zéro, Z représente -CH2- ou -O-; alors que lorsque n est égal à 1, Z représente -CH2-, -O- ou -S-; b) lorsque A représente $g(a) ou $g(b), où R3 représente l'hydrogène, alors n est égal à 1; et c) lorsque simultanément A représente $g(b), où R3 représente l'hydrogène, Z représente -CH2-, n est égal à 1 et R2 représente -COOR', où R' est défini ci-dessus, alors au moins l'un des éléments R et R1 est autre que l'hydrogène. De tels dérivés sont utiles dans le traitement de maladies relatives à un accroissement de la synthèse de thromboxane A2(TxA2).