7-(2-ethoxycarbonyl-1-methyl-ethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester | 280142-88-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 7-(2-ethoxycarbonyl-1-methyl-ethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 7-(4-ethoxy-4-oxobutan-2-yl)-3,4-dihydro-2H-quinoxaline-1-carboxylate
• CAS: 280142-88-3
• 化学式: C₁₉H₂₈N₂O₄
• 分子量: 348.442
• InChiKey: GPVKJGSLNXGQBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-(2-ethoxycarbonyl-1-methyl-ethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester 、 3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetic acid 在 4-二甲氨基吡啶 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 为溶剂， 反应 23.0h， 生成 7-(2-ethoxycarbonyl-1-methyl-ethyl)-4-{[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetyl}-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Dihydro-benzo(1,4)oxazines

  摘要：

  该发明涉及公式（I）的生理活性化合物：其中R1表示R3—Z3—，R3—L2—R4—Z3—，R3—L3—Ar1—L4—Z3—或R3—L3—Ar1—L2—R4—Z3—;R2表示氢，卤素，低碳基或低氧基；A1表示一条直链C2-3烷基链，可选地被来自烷基，芳基，芳基烷基，杂芳基，杂芳基烷基，亚胺基，氧代，硫代氧代，或由—ZR6，—NY1Y2，—CO2R6或—C(═O)—NY1Y2取代的一个或多个基团取代；L1表示直接键；烯基烷基，烷基，炔基烷基，环烯基，环烷基，杂芳基二基，杂环烷基或芳基链，每个链都可选地被(a)酸性官能团，氰基，氧代，—S(O)mR9，R3，—C(═O)—R3，—C(═O)—OR3，—N(R8)—C(═O)—R9，—N(R8)—C(═O)—OR9，—N(R8)—SO2—R9，—NY4Y5或—[C(═O)—N(R10)—C(R5)(R11)]p—C(═O)—NY4Y5取代，或(b)被酸性官能团或S(O)mR9，—C(═O)—NY4Y5或—NY4Y5取代的烷基取代；—[C(═O)—N(R10)—C(R5)(R11)]p—链；—Z2—R12—链；—C(═O)—CH2—C(═O)—链；—R12—Z2—R12—链；—C(R4)(R13)—[C(═O)—N(R10)—C(R5)(R11)]p—链；或—L5—L6—L7—链；Z1为NR17或O；Y为羧基或酸生物异构体；以及相应的N-氧化物和它们的前药；以及这些化合物及其N-氧化物和前药的药学上可接受的盐和溶剂物。这些化合物具有有价值的药理学特性，特别是调节VCAM-1和纤维连接蛋白与整合素VLA-4（α4β1）相互作用的能力。

  公开号：

  US06632814B1
• 作为产物：
  描述：

  4-benzyl-7-(2-ethoxycarbonyl-1-methyl-vinyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester 在 palladium dihydroxide 氢气 作用下， 以 溶剂黄146 为溶剂， 15.0 ℃ 、3.0 MPa 条件下， 生成 7-(2-ethoxycarbonyl-1-methyl-ethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Dihydro-benzo(1,4)oxazines

  摘要：

  该发明涉及公式（I）的生理活性化合物：其中R1表示R3—Z3—，R3—L2—R4—Z3—，R3—L3—Ar1—L4—Z3—或R3—L3—Ar1—L2—R4—Z3—;R2表示氢，卤素，低碳基或低氧基；A1表示一条直链C2-3烷基链，可选地被来自烷基，芳基，芳基烷基，杂芳基，杂芳基烷基，亚胺基，氧代，硫代氧代，或由—ZR6，—NY1Y2，—CO2R6或—C(═O)—NY1Y2取代的一个或多个基团取代；L1表示直接键；烯基烷基，烷基，炔基烷基，环烯基，环烷基，杂芳基二基，杂环烷基或芳基链，每个链都可选地被(a)酸性官能团，氰基，氧代，—S(O)mR9，R3，—C(═O)—R3，—C(═O)—OR3，—N(R8)—C(═O)—R9，—N(R8)—C(═O)—OR9，—N(R8)—SO2—R9，—NY4Y5或—[C(═O)—N(R10)—C(R5)(R11)]p—C(═O)—NY4Y5取代，或(b)被酸性官能团或S(O)mR9，—C(═O)—NY4Y5或—NY4Y5取代的烷基取代；—[C(═O)—N(R10)—C(R5)(R11)]p—链；—Z2—R12—链；—C(═O)—CH2—C(═O)—链；—R12—Z2—R12—链；—C(R4)(R13)—[C(═O)—N(R10)—C(R5)(R11)]p—链；或—L5—L6—L7—链；Z1为NR17或O；Y为羧基或酸生物异构体；以及相应的N-氧化物和它们的前药；以及这些化合物及其N-氧化物和前药的药学上可接受的盐和溶剂物。这些化合物具有有价值的药理学特性，特别是调节VCAM-1和纤维连接蛋白与整合素VLA-4（α4β1）相互作用的能力。

  公开号：

  US06632814B1

文献信息

• DIHYDRO-BENZO(1,4)OXAZINES AND TETRAHYDROQUINOXALINES
  申请人：Aventis Pharma Limited

  公开号：EP1056728A1

  公开（公告）日：2000-12-06
• US6632814B1
  申请人：——

  公开号：US6632814B1

  公开（公告）日：2003-10-14
• [EN] DIHYDRO-BENZO(1,4)OXAZINES AND TETRAHYDROQUINOXALINES<br/>[FR] DIHYDRO-BENZO(1,4)OXAZINES ET TETRAHYDROQUINOXALINES
  申请人：RHONE POULENC RORER LTD

  公开号：WO2000039103A1

  公开（公告）日：2000-07-06

  The invention is directed to physiologically active compounds of formula (I) wherein R1 represents R?3-Z3, R3-L2-R4-Z3-, R3-L3-Ar1-L4-Z3- or R3-L3-Ar1-L2-R4-Z3-; R2¿ represents hydrogen, halogen, lower alkyl or lower alkoxy; A1 represents a straight chain C¿2-3?alkylene linkage optionally substituted by one or more groups chosen from alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, imino, oxo, thioxo, or alkyl substituted by -ZR?6, -NY1Y2, -CO¿2R6 or -C(=O)-NY1Y2; L1 represents a direct bond; an alkenylene, alkylene, alkynylene, cycloalkenylene, cycloalkylene, heteroaryldiyl, heterocycloalkylene or arylene linkage each optionally substituted by (a) an acidic functional group, cyano, oxo, -S(O)¿mR?9, R3, -C(=O)-R3, -C(=O)-OR?3, -N(R8¿)-C(=O)-R?9, -N(R8¿)-C(=O)-OR?9, -N(R8)-SO¿2-R?9, -NY4Y5¿ or -[C(=O)-N(R?10)-C(R5)(R11)]¿p-C(=O)-NY4Y5, or by (b) alkyl substituted by an acidic functional group, or by S(O)¿mR?9, -C(=O)-NY?4Y5 or -NY4Y5¿; a -[C(=O)-N(R?10)-C(R5)(R11)]¿p-linkage; a-Z2-R12-linkage; a -C(=O)-CH¿2?-C(=O)-linkage; a -R?12-Z2-R12¿- linkage; a -C(R4)(R13)-[C(=O)-N(R?10)-C(R5)(R11)]¿p- linkage; or a -L5-L6-L7- linkage; Z?1 is NR17¿ or O; Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (α4β1).
• Dihydro-benzo(1,4)oxazines
  申请人：Aventis Pharma Ltd.

  公开号：US06632814B1

  公开（公告）日：2003-10-14

  The invention is directed to physiologically active compounds of formula (I): wherein R1 represents R3—Z3—, R3—L2—R4—Z3—, R3—L3—Ar1—L4—Z3— or R3—L3—Ar1—L2—R4—Z3—; R2 represents hydrogen, halogen, lower alkyl or lower alkoxy; A1 represents a straight chain C2-3alkylene linkage optionally substituted by one or more groups chosen from alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, imino, oxo, thioxo, or alkyl substituted by —ZR6, —NY1Y2, —CO2R6 or —C(═O)—NY1Y2; L1 represents a direct bond; an alkenylene, alkylene, alkynylene, cycloalkenylene, cycloalkylene, heteroaryldiyl, heterocycloalkylene or arylene linkage each optionally substituted by (a) an acidic functional group, cyano, oxo, —S(O)mR9, R3, —C(═O)—R3, —C(═O)—OR3, —N(R8)—C(═O)—R9, —N(R8)—C(═O)—OR9, —N(R8)—SO2—R9, —NY4Y5 or —[C(═O)—N(R10)—C(R5)(R11)]p—C(═O)—NY4Y5, or by (b) alkyl substituted by an acidic functional group, or by S(O)mR9, —C(═O)—NY4Y5 or —NY4Y5; a —[C(═O)—N(R10)—C(R5)(R11)]p— linkage; a —Z2—R12— linkage; a —C(═O)—CH2—C(═O)— linkage; a —R 12—Z2—R12— linkage; a —C(R4)(R13)—[C(═O)—N(R10)—C(R5)(R11)]p— linkage; or a —L5—L6—L7— linkage; Z1 is NR17 or O; Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (&agr;4&bgr;1).

  该发明涉及公式（I）的生理活性化合物：其中R1表示R3—Z3—，R3—L2—R4—Z3—，R3—L3—Ar1—L4—Z3—或R3—L3—Ar1—L2—R4—Z3—;R2表示氢，卤素，低碳基或低氧基；A1表示一条直链C2-3烷基链，可选地被来自烷基，芳基，芳基烷基，杂芳基，杂芳基烷基，亚胺基，氧代，硫代氧代，或由—ZR6，—NY1Y2，—CO2R6或—C(═O)—NY1Y2取代的一个或多个基团取代；L1表示直接键；烯基烷基，烷基，炔基烷基，环烯基，环烷基，杂芳基二基，杂环烷基或芳基链，每个链都可选地被(a)酸性官能团，氰基，氧代，—S(O)mR9，R3，—C(═O)—R3，—C(═O)—OR3，—N(R8)—C(═O)—R9，—N(R8)—C(═O)—OR9，—N(R8)—SO2—R9，—NY4Y5或—[C(═O)—N(R10)—C(R5)(R11)]p—C(═O)—NY4Y5取代，或(b)被酸性官能团或S(O)mR9，—C(═O)—NY4Y5或—NY4Y5取代的烷基取代；—[C(═O)—N(R10)—C(R5)(R11)]p—链；—Z2—R12—链；—C(═O)—CH2—C(═O)—链；—R12—Z2—R12—链；—C(R4)(R13)—[C(═O)—N(R10)—C(R5)(R11)]p—链；或—L5—L6—L7—链；Z1为NR17或O；Y为羧基或酸生物异构体；以及相应的N-氧化物和它们的前药；以及这些化合物及其N-氧化物和前药的药学上可接受的盐和溶剂物。这些化合物具有有价值的药理学特性，特别是调节VCAM-1和纤维连接蛋白与整合素VLA-4（α4β1）相互作用的能力。