(+/-)-4,5-dihydro-3-(3-pyridinyl)-N-[4-(3-pyridinylcarbonyl)phenyl]-5-isoxazolecarboxamide | 264605-15-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (+/-)-4,5-dihydro-3-(3-pyridinyl)-N-[4-(3-pyridinylcarbonyl)phenyl]-5-isoxazolecarboxamide
• 英文别名: 4,5-dihydro-3-(3-pyridinyl)-N-[4-(3-pyridinylcarbonyl)phenyl]-5-isoxazolecarboxamide；N-[4-(pyridine-3-carbonyl)phenyl]-3-pyridin-3-yl-4,5-dihydro-1,2-oxazole-5-carboxamide
• CAS: 264605-15-4
• 化学式: C₂₁H₁₆N₄O₃
• 分子量: 372.383
• InChiKey: JVXHMNVDQQPUPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  93.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-4,5-dihydro-3-(3-pyridinyl)-N-[4-(3-pyridinylcarbonyl)phenyl]-5-isoxazolecarboxamide 、 sodium acetate 在 羟胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以18%的产率得到4,5-dihydro-N-[4-[(hydroxyimino)-3-pyridinylmethyl]phenyl]-3-(3-pyridinyl)-5-isoxazolecarboxamide
  参考文献：
  名称：

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

  摘要：

  本发明涉及以下式中的化合物，其中m、n和p分别独立地为0或1，q为0、1、2、3、4或5；—A1═A2—A3═A4—为吡啶基、吡啶并嗪基、嘧啶基、吡嗪基或苯基；B代表酰胺、酮或噁二唑基；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、亚砜基、3-氧代丁烯基、吡唑、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、胍胺基、硝基、NR17R18、可选择取代的C(1-6)烷基或C(1-6)烷氧基；R2和R3分别独立地代表氢、卤素、C(1-6)烷氧基或可选择取代的C(1-6)烷基；R5和R6分别独立地代表氢、羟基、卤素、可选择取代的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代表可选择取代的C(6-14)芳基；Het代表可选择取代的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。进一步涉及它们作为药物的用途。

  公开号：

  US06583141B1

文献信息

• 4,5-Dihydro-isoxazole derivatives and their pharmaceutical use
  申请人：——

  公开号：US20040019059A1

  公开（公告）日：2004-01-29

  The present invention is concerned with the compounds of formula 1 wherein m, n and p are each independently 0 or 1 and q is 0, 1, 2, 3, 4 or 5; -A 1 =A 2 -A 3 =A 4 - 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—, —CR 5 R 6 —, amide, ethenyl, imine, sulfonyl, sulfinyl, 3-oxobutenyl, pyrazole, isoxazole or thiazole; L represents Ar or Het; R 1 represents hydrogen, halo, hydroxy, C (2-6) alkenyl, C (2-6) alkynyl, C (3-6) cycloalkyl, C (3-6) cycloalkenyl, cyano, guanidine, nitro, NR 17 R 18 , an optionally substituted C (1-6) alkyl or C (I6) alkyloxy; R 2 and R 3 each independently represent hydrogen, halo, C (1-6) alkyloxy or an optionally substituted C (1-6) alkyl; R 5 and R 6 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)R 25 , (C—O)OR 16 , (SO 2 )R 16 , aminocarbonyloxy, aminoC (1-6) alkyl, NR 17 R 18 , N 3 , Ar or Het; or R 5 and R 6 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。
• 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.