(+/-)-[cyano-[4-[[[4,5-dihydro-3-(3-pyridinyl)-5-isoxazolyl]carbonyl]amino]-phenyl]phenylmethyl] acetate | 264603-90-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+/-)-[cyano-[4-[[[4,5-dihydro-3-(3-pyridinyl)-5-isoxazolyl]carbonyl]amino]-phenyl]phenylmethyl] acetate
• 英文别名: (+/-)-[Cyano-[4-[[[4,5-dihydro-3-(3-pyridinyl)-5-isoxazolyl]carbonyl]amino]phenyl]-phenylmethyl]acetate；[cyano-phenyl-[4-[(3-pyridin-3-yl-4,5-dihydro-1,2-oxazole-5-carbonyl)amino]phenyl]methyl] acetate
• CAS: 264603-90-9
• 化学式: C₂₅H₂₀N₄O₄
• 分子量: 440.458
• InChiKey: OCXADHBALRXDCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  乙酸酐 、 (+/-)-N-[4-(cyanohydroxyphenylmethyl)phenyl]-4,5-dihydro-3-(3-pyridinyl)-5-isoxazolecarboxamide 在 乙酸乙酯 、 水 、 Sodium sulfate-III 、 silica gel 、 methanol-dichloromethane 作用下， 以 吡啶 为溶剂， 反应 96.0h， 以yielding 2.7 g (61%) of (±)-[cyano-[4-[[[4,5-dihydro-3-(3-pyridinyl)-5-isoxazolyl]carbonyl]amino]phenyl]-phenylmethyl]acetate的产率得到(+/-)-[cyano-[4-[[[4,5-dihydro-3-(3-pyridinyl)-5-isoxazolyl]carbonyl]amino]-phenyl]phenylmethyl] acetate
  参考文献：
  名称：

  4,5-Dihydro-isoxazole derivatives and their pharmaceutical use

  摘要：

  本发明涉及公式1的化合物，其中m、n和p各自独立地为0或1，q为0、1、2、3、4或5；-A1=A2-A3=A4-为吡啶基亚甲基、吡嗪基亚甲基、嘧啶基亚甲基、吡嗪基亚甲基或苯基亚甲基；B代表酰胺、酮或噁二唑；D代表Ar或Het；Q代表共价直接键或酮、-N-、-O-、-CR5R6-、酰胺、乙烯基、亚胺、磺酰基、亚磺酰基、3-氧代丁烯基、吡唑、异唑或噻唑；L代表Ar或Het；R1代表氢、卤素、羟基、C（2-6）烯基、C（2-6）炔基、C（3-6）环烷基、C（3-6）环烯基、氰基、鸟氨酸基、硝基、NR17R18、可选取代的C（1-6）烷基或C（I6）烷氧基；R2和R3各自独立地代表氢、卤素、C（1-6）烷氧基或可选取代的C（1-6）烷基；R5和R6各自独立地代表氢、羟基、卤素、可选取代的C（1-6）烷基、C（2-6）烯基、C（2-6）炔基、C（3-6）环烷基、C（3-6）环烯基、C（1-6）烷氧基、氰基、（C═O）R25、（C-O）OR16、（SO2）R16、氨基羰氧基、氨基C（1-6）烷基、NR17R18、N3、Ar或Het；或者R5和R6与它们连接的碳原子一起形成Ar或Het；Ar代表可选取代的C（6-14）芳基；Het代表可选取代的C（1-14）杂环；或者它们的N-氧化物、药学上可接受的加合盐、季铵盐或立体化学异构体形式；以及它们作为药物的用途。

  公开号：

  US20040019059A1

文献信息

• 4,5-dihydro-isoxazole derivatives and their pharmaceutical use
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US07414048B2

  公开（公告）日：2008-08-19

  The present invention is concerned with the compounds of formula wherein m, n and p are each independently 0 or 1 and q is 0, 1, 2, 3, 4 or 5; -A1=A2-A3=A4- is a pyridinylidene, pyridazinylidene, pyrimidinylidene, pyrazinylidene or phenylidene; B represents an amide, ketone or oxadiazole; D represents Ar or Het; Q represents a covalent direct bond or a ketone, —N—, —O—, —CR5R6—, amide, ethenyl, imine, sulfonyl, sulfinyl, 3-oxobutenyl, pyrazole, isoxazole or thiazole; L represents Ar or Het; R1 represents hydrogen, halo, hydroxy, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, cyano, guanidine, nitro, NR17R18, an optionally substituted C(1-6)alkyl or C(1-6)alkyloxy; R2 and R3 each independently represent hydrogen, halo, C(1-6)alkyloxy or an optionally substituted C(1-6)alkyl; R5 and R6 each independently represent hydrogen, hydroxy, halo, an optionally substituted C(1-6)alkyl, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, C(1-6)alkyloxy, cyano, (C═O)R25, (C—O)OR16, (SO2)R16, aminocarbonyloxy, aminoC(1-6)alkyl, NR17R18, N3, Ar or Het; or R5 and R6 together with the carbon atom to which they are attached, form an Ar or Het; Ar represents an optionally substituted C(6-14)aryl; Het represents an optionally substituted C(1-14)heterocycle; or a N-oxide, pharmaceutically acceptable addition salt, quaternary amine or stereochemically isomeric form thereof; the processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

  本发明涉及以下式的化合物，其中m、n和p各自独立地为0或1，q为0、1、2、3、4或5；-A1 = A2-A3 = A4-为吡啶基烯、吡嗪基烯、嘧啶基烯、吡嗪基烯或苯基烯；B代表酰胺、酮或噁二唑；D代表Ar或Het；Q代表共价直接键或酮，-N-，-O-，-CR5R6-，酰胺，乙烯基，亚胺，磺酰基，亚磺酰基，3-氧代丁烯基，吡唑烷，异噁唑或噻唑；L代表Ar或Het；R1代表氢、卤素、羟基、C（2-6）烯基、C（2-6）炔基、C（3-6）环烷基、C（3-6）环烯基、氰基、胍、硝基、NR17R18、可选取代的C（1-6）烷基或C（1-6）烷氧基；R2和R3各自独立地代表氢、卤素、C（1-6）烷氧基或可选取代的C（1-6）烷基；R5和R6各自独立地代表氢、羟基、卤素、可选取代的C（1-6）烷基、C（2-6）烯基、C（2-6）炔基、C（3-6）环烷基、C（3-6）环烯基、C（1-6）烷氧基、氰基、（C═O）R25、（C—O）OR16、（SO2）R16、氨基羰氧基、氨基C（1-6）烷基、NR17R18、N3、Ar或Het；或R5和R6与它们连接的碳原子一起形成Ar或Het；Ar代表可选取代的C（6-14）芳基；Het代表可选取代的C（1-14）杂环；或其N-氧化物、药学上可接受的加合盐、季铵盐或立体化学异构体形式；以及它们的制备方法和包含它们的组合物。它还涉及它们作为药物的用途。
• 4,5-DIHYDRO-ISOXAZOLE DERIVATIVES AND THEIR PHARMACEUTICAL USE
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1119568A1

  公开（公告）日：2001-08-01
• US6583141B1
  申请人：——

  公开号：US6583141B1

  公开（公告）日：2003-06-24
• US7414048B2
  申请人：——

  公开号：US7414048B2

  公开（公告）日：2008-08-19
• [EN] 4,5-DIHYDRO-ISOXAZOLE DERIVATIVES AND THEIR PHARMACEUTICAL USE<br/>[FR] DERIVES DE 4-5-DIHYDRO-ISOXAZOLE ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2000021959A1

  公开（公告）日：2000-04-20

  The present invention is concerned with the compounds of formula (I), wherein m, n and p are each independently 0 or 1 and q is 0, 1, 2, 3, 4 or 5; A?1=A2 A3=A4¿ is pyridinylidene, pyridazinylidene, pyrimidinylidene, pyrazinylidene or phenylidene; B represents an amide, ketone or oxadiazole; D represents Ar or Het; Q represents a covalent direct bond or a ketone, -N-, -O-, -CR5R6-, amide, ethenyl, imine, sulfonyl, sulfinyl, 3-oxobutenyl, pyrazole isoxazole or thiazole; L represents Ar or Het; R1 represents hydrogen, halo, hydroxy C¿(2-6)?alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, cyano, guanidine, nitro NR?17R18¿, an optionally substituted C¿(1-6)?alkyl or C(1-6)alkyloxy; R?2 and R3¿ each independently represent hydrogen, halo, C¿(1-6)?alkyloxy or an optionally substituted C(1-6)alkyl; R?5 and R6¿ each independently represent hydrogen, hydroxy, halo, an optionally substituted C¿(1-6)?alkyl, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloaklyl, C(3-6)cycloalkenyl, C(1-6)alkyloxy, cyano, (C=O)R?25¿, (C=O)OR16, (SO2)R16, aminocarbonyloxy, amino C¿(1-6)?alkyl, NR?17R18, N¿3, Ar or Het; or R?5 and R6¿ together with the carbon atom to which they are attached, form an Ar or Het; Ar represents an optionally substituted C¿(6-14)?aryl; Het represents an optionally substituted C(1-14)heterocycle; or a N-oxide, pharmaceutically acceptable addition salt, quaternary amine or stereochemically isomeric form thereof; the process for their preparation and compositions comprising them. It further relates to their use as a medicine.