6-amino-3,4-dihydro-4-<2-(dimethylamino)ethyl>-2H-1,4-benzoxazine | 174567-31-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-amino-3,4-dihydro-4-<2-(dimethylamino)ethyl>-2H-1,4-benzoxazine
• 英文别名: 4-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine；6-Amino-3,4-dihydro-4-(2-dimethylaminoethyl)-2H-1,4-benzoxazine；4-[2-(dimethylamino)ethyl]-2,3-dihydro-1,4-benzoxazin-6-amine
• CAS: 174567-31-8
• 化学式: C₁₂H₁₉N₃O
• 分子量: 221.302
• InChiKey: XTFSDBKVWBFHAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-amino-3,4-dihydro-4-<2-(dimethylamino)ethyl>-2H-1,4-benzoxazine 、 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-biphenyl-4-carbonyl chloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 以30%的产率得到N-[4-(2-Dimethylaminoethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide
  参考文献：
  名称：

  The Selective 5-HT_1B Receptor Inverse Agonist 1‘-Methyl-5-[[2‘-methyl-4‘- (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4‘-piperidine] (SB-224289) Potently Blocks Terminal 5-HT Autoreceptor Function Both in Vitro and in Vivo

  摘要：

  5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are negatively Linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D receptors (previously known as 5-HT1D beta and 5-HT1D alpha, respectively), although encoded by two distinct genes, are structurally very similar. Pharmacologically, these two receptors have been differentiated using nonselective chemical tools such as ketanserin and ritanserin, but the absence of truly selective agents has meant that the precise function of the 5-HT1B and 5-HT1D receptors has not been defined. In this paper we describe how, using computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D receptor antagonist 4 was structurally modified to produce the selective 5-HT1B receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT autoreceptor function both in vitro and in vivo.

  DOI：

  10.1021/jm970457s
• 作为产物：
  描述：

  3,4-dihydro-4-<2-(dimethylamino)ethyl>-6-nitro-2H-1,4-benzoxazine 在 钯 氩 、 乙醇 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 6-amino-3,4-dihydro-4-<2-(dimethylamino)ethyl>-2H-1,4-benzoxazine
  参考文献：
  名称：

  Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity

  摘要：

  本发明涉及抑制一氧化氮合酶（NOS）的苯并噻嗪，特别是那些选择性抑制神经元一氧化氮合酶（nNOS）而不是其他NOS亚型的化合物，其化学式为：本发明的NOS抑制剂可以单独或与其他药物活性剂联合使用，用于治疗或预防各种医疗状况。

  公开号：

  US08106043B2

文献信息

• BENZOXAZINES, BENZOTHIAZINES, AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
  申请人：Ramnauth Jailall

  公开号：US20100009975A1

  公开（公告）日：2010-01-14

  The present invention features benzoxazines, benzothiazines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.

  本发明涉及抑制一氧化氮合酶（NOS）的苯并噁嗪，苯并噻嗪和相关化合物，特别是那些选择性地抑制神经一氧化氮合酶（nNOS）而不是其他NOS同工型的化合物。本发明的NOS抑制剂，单独或与其他药用活性剂结合使用，可用于治疗或预防各种医疗状况。
• Melanin concentrating hormone antagonist
  申请人：Kato Kaneyoshi

  公开号：US20070173498A1

  公开（公告）日：2007-07-26

  A melanin-concentrating hormone antagonist which comprises a compound of the formula: wherein Ar 1 is a cyclic group which may have substituents; X is a spacer having a main chain of 1 to 6 atoms; Y is a bond or a spacer having a main chain of 1 to 6 atoms; Ar is a monocyclic aromatic ring which may be condensed with a 4 to 8 membered non-aromatic ring, and may have further substituents; R 1 and R 2 are independently hydrogen atom or a hydrocarbon group which may have substituents; R 1 and R 2 , together with the adjacent nitrogen atom, may form a nitrogen-containing hetero ring which may have substituents; R 2 may form a spiro ring together with Ar; or R 2 , together with the adjacent nitrogen atom and Y, may form a nitrogen-containing hetero ring which may have substituents; or a salt thereof; which is useful as an agent for preventing or treating obesity, etc.

  一种黑色素浓集激素拮抗剂，包括一个化合物，其化学式为：其中Ar1是一个环状基团，可能具有取代基；X是一个具有1到6个原子主链的间隔物；Y是一条键或具有1到6个原子主链的间隔物；Ar是一个单环芳香环，可以与一个4到8个成员的非芳香环融合，并且可能有进一步的取代基；R1和R2分别是氢原子或一个可能具有取代基的碳氢基团；R1和R2连同相邻的氮原子可以形成一个含氮杂环，该杂环可能具有取代基；R2可以与Ar一起形成一个螺环；或者R2连同相邻的氮原子和Y可以形成一个含氮杂环，该杂环可能具有取代基；或其盐；用作预防或治疗肥胖等的药剂。
• Biphenyl(thio)amide and bipennylethan(thi) one derivatives, their
  申请人：SmithKline Beecham p.l.c.

  公开号：US05972935A1

  公开（公告）日：1999-10-26

  The invention relates to novel heterocyclic compounds of formula (I) or a salt or N-oxide thereof, in which R is a group of formulae (i), (ii) or (iii), where R.sup.1 is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, COC.sub.1-6 akyl, C.sub.1-6 alkoxy, hydroxy, hydroxyC.sub.1-6 alkyl, hydroxyC.sub.1-6 alkoxy, C.sub.1-6 alkoxyC.sub.1-6 alkoxy, acyle, nitro, trifluoromethyl, cyano, SR.sup.9, SOR.sup.9, SO.sub.2 R.sup.9, NR.sup.9 CONR.sup.10 R.sup.11, NR.sup.10 SO.sub.2 R.sup.11, SO.sub.2 NR.sup.11 r.sup.11, SO.sub.2 NR.sup.10 R.sup.11, CO.sub.2 R.sup.10, CONR.sup.10 R.sup.11, CO.sub.2 NR.sup.10 R.sup.11, CONR.sup.10 (CH.sub.2).sub.a CO.sub.2 R.sup.11, (CH.sub.2).sub.a NR.sup.10 R.sup.11, ##STR1## (CH.sub.2).sub.a CONR.sup.10 R.sup.11, (CH.sub.2).sub.a COR.sup.11, (CH.sub.2).sub.a CO.sub.2 C.sub.1-6 alkyl, CO.sub.2 (CH.sub.2).sub.a OR.sup.10, NR.sup.10 R.sup.11, N.dbd.CNR.sup.9 NR.sup.10 R.sup.11, NR.sup.10 CO(CH.sub.2).sub.a NR.sup.10 R.sup.11, NR.sup.10 CO.sub.2 R.sup.11, CONHNR.sup.10 R.sup.11, CR.sup.10 .dbd.NOR.sup.11, CNR.sup.10 .dbd.NOR.sup.11, where R.sup.9, R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl and a is 1 to 4; or R.sup.1 is a group --X--R.sup.12 where R.sup.12 is an optionally substituted 5- to 7-membered heterocyclic ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulphur and X is a bond, O, S, CH.sub.2, C.dbd.O, NR.sup.13 CO or NR.sup.13 where R.sup.13 is hydrogen or C.sub.1-6 alkyl; R.sup.4 and R.sup.5 are independently hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, C.sub.1-6 alkoxy, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylOC.sub.1-6 alkyl, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO.sub.2 R.sup.10, CONR.sup.10 R.sup.11, NR.sup.10 R.sup.11 where R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl, or R.sup.4 and R.sup.5 together form a group --CH.sub.2).sub.r --R.sup.14 --(CH.sub.2).sub.s -- where R.sup.14 is O, S, CH.sub.2 or NR.sup.15 where R.sup.15 is hydrogen or C.sub.1-6 alkyl and r and s are independently 0, 1 or 2; R.sup.2 is hydrogen, C.sub.1-6 alkyl, optionally substituted aryl or optionally substituted heteroaryl; R.sup.3 is hydrogen or C.sub.1-6 alkyl or together with R.sup.8 forms a group (CH.sub.2).sub.q where q is 2, 3 or 4; Z is oxygen or sulphur, p is 1 or 2; P is an optionally substituted bicyclic ring optionally containing one to four heteroatoms; or P is an optionally substituted 5- to 7-membered saturated or partially saturated ring optionally containing one to three heteroatoms; and B is oxygen or sulphur, D is nitrogen, carbon or a CH group; R.sup.6 is hydrogen or C.sub.1-6 alkyl and R.sup.7 is C.sub.1-6 alkyl, C.sub.1-6 alkoxy or halogen, or R.sup.6 together with R.sup.7 forms a group --A-- where A is (CR.sup.16 R.sup.17).sub.t where t is 1, 2 or 3 and R.sup.16 and R.sup.17 are independently hydrogen or C.sub.1-6 alkyl or A is (CR.sup.16 R.sup.17).sub.u --J where u is 0, 1, or 2 and J is oxygen, sulphur, CR.sup.16 .dbd.C.sup.17, CR.sup.16 .dbd.N, CR.sup.16 NR.sup.17 or N.dbd.N; R.sup.18 and R.sup.19 are independently hydrogen or C.sub.1-6 alkyl; R.sup.20 and R.sup.21 are independently hydrogen, C.sub.1-6 alkyl, aralkyl, or together with the nitrogen atom to which they are attached form an optionally substituted 5- to 7-membered heterocyclic ring containing one or two heteroatoms selected from oxygen, nitrogen or sulphur, m is 0 to 4; and Q is an optionally substituted 5- to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur, processes for their preparation, and their use as 5-HT.sub.1D receptor antagonists.

  本发明涉及式（I）的新型杂环化合物或其盐或N-氧化物，其中R是式（i），（ii）或（iii）的基团，其中R.sup.1是氢，卤素，C.sub.1-6烷基，C.sub.3-6环烷基，COC.sub.1-6烷基，C.sub.1-6烷氧基，羟基，羟基C.sub.1-6烷基，羟基C.sub.1-6烷氧基，C.sub.1-6烷氧基C.sub.1-6烷氧基，酰基，硝基，三氟甲基，氰基，SR.sup.9，SOR.sup.9，SO.sub.2R.sup.9，NR.sup.9CONR.sup.10R.sup.11，NR.sup.10SO.sub.2R.sup.11，SO.sub.2NR.sup.11r.sup.11，SO.sub.2NR.sup.10R.sup.11，CO.sub.2R.sup.10，CONR.sup.10R.sup.11，CO.sub.2NR.sup.10R.sup.11，CONR.sup.10（CH.sub.2）.sub.aCO.sub.2R.sup.11，（CH.sub.2）.sub.aNR.sup.10R.sup.11，##STR1##（CH.sub.2）.sub.aCONR.sup.10R.sup.11，（CH.sub.2）.sub.aCOR.sup.11，（CH.sub.2）.sub.aCO.sub.2C.sub.1-6烷基，CO.sub.2（CH.sub.2）.sub.aOR.sup.10，NR.sup.10R.sup.11，N.dbd.CNR.sup.9NR.sup.10R.sup.11，NR.sup.10CO（CH.sub.2）.sub.aNR.sup.10R.sup.11，NR.sup.10CO.sub.2R.sup.11，CONHNR.sup.10R.sup.11，CR.sup.10.dbd.NOR.sup.11，CNR.sup.10.dbd.NOR.sup.11，其中R.sup.9，R.sup.10和R.sup.11独立地为氢或C.sub.1-6烷基，a为1至4；或R.sup.1为--X--R.sup.12的基团，其中R.sup.12是含有1至4个氧，氮或硫杂原子的可选择取代的5-至7元杂环环，X为键，O，S，CH.sub.2，C.dbd.O，NR.sup.13CO或NR.sup.13，其中R.sup.13为氢或C.sub.1-6烷基；R.sup.4和R.sup.5独立地为氢，卤素，C.sub.1-6烷基，C.sub.3-6环烷基，C.sub.3-6环烯基，C.sub.1-6烷氧基，羟基C.sub.1-6烷基，C.sub.1-6烷氧基C.sub.1-6烷基，酰基，芳基，酰氧基，羟基，硝基，三氟甲基，氰基，CO.sub.2R.sup.10，CONR.sup.10R.sup.11，NR.sup.10R.sup.11，其中R.sup.10和R.sup.11独立地为氢或C.sub.1-6烷基，或R.sup.4和R.sup.5一起形成基团--CH.sub.2）.sub.r--R.sup.14--（CH.sub.2）.sub.s--，其中R.sup.14为O，S，CH.sub.2或NR.sup.15，其中R.sup.15为氢或C.sub.1-6烷基，r和s独立地为0，1或2；R.sup.2为氢，C.sub.1-6烷基，可选择取代的芳基或可选择取代的杂芳基；R.sup.3为氢或C.sub.1-6烷基，或与R.sup.8一起形成基团（CH.sub.2）.sub.q，其中q为2、3或4；Z为氧或硫，p为1或2；P是可选择取代的双环环，可选择包含一到四个杂原子；或P是可选择取代的5-至7元饱和或部分饱和环，可选择包含一到三个杂原子；B为氧或硫，D为氮，碳或CH基团；R.sup.6为氢或C.sub.1-6烷基，R.sup.7为C.sub.1-6烷基，C.sub.1-6烷氧基或卤素，或R.sup.6与R.sup.7一起形成基团--A--，其中A为（CR.sup.16R.sup.17）.sub.t，其中t为1、2或3，R.sup.16和R.sup.17独立地为氢或C.sub.1-6烷基，或A为（CR.sup.16R.sup.17）.sub.u--J，其中u为0、1或2，J为氧，硫，CR.sup.16.dbd.C.sup.17，CR.sup.16.dbd.N，CR.sup.16NR.sup.17或N.dbd.N；R.sup.18和R.sup.19独立地为氢或C.sub.1-6烷基；R.sup.20和R.sup.21独立地为氢，C.sub.1-6烷基，芳基烷基，或与它们所连接的氮原子一起形成可选择取代的5-至7元杂环环，其中选自氧，氮或硫的一个或两个杂原子，m为0至4；Q为可选择取代的5-至7元杂环环，其中选自氧，氮或硫的1至3个杂原子，以及它们的制备方法和作为5-HT.sub.1D受体拮抗剂的用途。
• AMIDE DERIVATIVES HAVING 5HT1D-ANTAGONIST ACTIVITY
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0763034A1

  公开（公告）日：1997-03-19
• BIPHENYL(THIO)AMIDE AND BIPHENYLETHAN(THI)ONE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS 5-HT 1D? RECEPTOR ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1019412A1

  公开（公告）日：2000-07-19