3-hydroxymethyl-1-methyl-2,3-dihydro-1H-[1,4]oxazin[2,3-b]pyridine | 383901-48-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-hydroxymethyl-1-methyl-2,3-dihydro-1H-[1,4]oxazin[2,3-b]pyridine
• 英文别名: 2,3-dihydro-1-methyl-1H-pyrido[2,3-b][1,4]oxazine-3-methanol；(1-Methyl-2,3-dihydropyrido[2,3-b][1,4]oxazin-3-yl)methanol
• CAS: 383901-48-2
• 化学式: C₉H₁₂N₂O₂
• 分子量: 180.206
• InChiKey: UMTLUFHVHBDTMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  45.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-hydroxymethyl-1-methyl-2,3-dihydro-1H-[1,4]oxazin[2,3-b]pyridine 在 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 反应 73.0h， 生成 3-[[4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl]methyl]-1-methyl-2,3-dihydropyrido[2,3-b][1,4]oxazine
  参考文献：
  名称：

  [EN] INDOLE DERIVATIVES WITH AN IMPROVED ANTIPSYCHOTIC ACTIVITY
  [FR] DERIVE D'INDOLE A ACTIVITE ANTIPSYCHOTIQUE AMELIOREE

  摘要：

  本发明涉及一种新颖的吲哚衍生物，其符合以下式（I）的药学上可接受的酸或碱盐，其立体化异构体形式，其N-氧化物形式或其季铵盐，其中变量R1、R2、R3、R4、R5、p、a1 = a2-a3 = a4、Z1-Z2、X和Y的定义如权利要求书中所述。所述衍生物具有与多巴胺受体的结合亲和力，特别是对多巴胺D2、D3和D4受体具有选择性的5-羟色胺再摄取抑制特性，并作为5-HT1A激动剂或部分激动剂。本发明还涉及包含根据本发明的化合物的药物组合物，其用于预防和/或治疗一系列精神疾病和神经系统疾病，特别是某些精神疾病，尤其是精神分裂症，以及其生产工艺。

  公开号：

  WO2004106298A1
• 作为产物：
  描述：

  2-氯-3-甲胺基吡啶 在 三氯化铁 、 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 生成 3-hydroxymethyl-1-methyl-2,3-dihydro-1H-[1,4]oxazin[2,3-b]pyridine
  参考文献：
  名称：

  3-取代的2,3-二氢-1,4-二氧杂[2,3- b ]吡啶的新型类似物：在二恶烷环上的修饰

  摘要：

  描述了在非芳族环上修饰的一系列3-取代的2,3-二氢-1,4-二恶英[2,3- b ]吡啶核的新型类似物的合成。由于在它们的结构中存在通用的羟甲基基团，所以这些新颖的支架是用于制备潜在的新治疗剂的有吸引力的中间体。

  DOI：

  10.1016/j.tetlet.2003.09.145

文献信息

• Compounds for treating impaired fundic relaxation
  申请人：——

  公开号：US20040019051A1

  公开（公告）日：2004-01-29

  The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharma-ceutically acceptable acid addition salt thereof, wherein —a 1 ═a 2 —a 3 ═a 4 — is a bivalent radical wherein one or two of a 1 to a 4 are nitrogen and the remaining a 1 to a 4 are —CH═; —Z 1 —Z 2 — is a bivalent radical; —A— is a bivalent radical of formula —N(R 6 )—Alk 2 — or a 5, 6 or 7-membered saturated heterocycle containing one or two nitrogen atoms; R 1 , R 2 and R 3 are each independently selected from hydrogen, C 1-6 alkyl, hydroxy, halo and the like; Alk 1 and Alk 2 are optionally substituted C 1-6 alkanediyl; R 5 is a radical of formula (d-1), (d-2), (d-3), (d-4), (d-5) wherein n is 1 or 2; p 1 is 0, and p 2 is 1 or 2; or p 1 is 1 or 2, and p 2 is 0; X is oxygen, sulfur or ═NR 9 ; Y 2 is oxygen or sulfur; R 7 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, phenyl or phenylmethyl; R 8 is C 1-6 alkyl, C 3-6 cycloalkyl phenyl or phenylmethyl; R 9 is cyano, C 1-6 alkyl, C 3-6 cyclo-alkyl, C 1-6 alkyloxycarbonyl or aminocarbonyl; R 10 is hydrogen or C 1-6 alkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to disturbed fundic accomodation. 1

  本发明涉及式（I）的化合物，其立体化学异构体形式，N-氧化物形式或药学上可接受的酸加合物盐形式，其中-a1═a2-a3═a4-是一个双价基团，其中a1到a4中的一个或两个是氮，其余的a1到a4是-CH═；-Z1—Z2-是一个双价基团；-A-是公式-N（R6）-Alk2-或含有一个或两个氮原子的5、6或7元饱和杂环的双价基团；R1、R2和R3各自独立地选自氢、C1-6烷基、羟基、卤素等；Alk1和Alk2是可选取代的C1-6烷二基；R5是公式（d-1）、（d-2）、（d-3）、（d-4）、（d-5）的基团，其中n为1或2；p1为0，p2为1或2；或p1为1或2，p2为0；X为氧、硫或═NR9；Y2为氧或硫；R7为氢、C1-6烷基、C3-6环烷基、苯基或苯甲基；R8为C1-6烷基、C3-6环烷基、苯基或苯甲基；R9为氰基、C1-6烷基、C3-6环烷基、C1-6烷氧羰基或氨基羰基；R10为氢或C1-6烷基；Q为双价基团。公开了制备所述产品的方法，包含所述产品的配方以及其用作药物的用途，特别是用于治疗与干扰胃底容积有关的疾病。
• Compounds for treating fundic disaccomodation
  申请人：Emelen Van Kristol

  公开号：US20060142318A1

  公开（公告）日：2006-06-29

  The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, wherein -a 1 =a 2 -a 3 =a 4 - is a bivalent radical wherein one or two of a 1 to a 4 are nitrogen and the remaining a 1 to a 4 are —CH═; -Z 1 -Z 2 - is a bivalent radical; -A- is a bivalent radical of formula —N(R 6 )-Alk 2 - or a 5, 6 or 7-membered saturated heterocycle containing one or two nitrogen atoms; R 1 , R 2 and R 3 are each independently selected from hydrogen, C 1-6 alkyl, hydroxy, halo and the like; Alk 1 and Alk 2 are optionally substituted C 1-6 alkanediyl; R 5 is a radical of formula wherein n is 1 or 2; p 1 is 0, and p 2 is 1 or 2; or p 1 is 1 or 2, and p 2 is 0; X is oxygen, sulfur or ═NR 9 ; Y 2 is oxygen or sulfur; R 7 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, phenyl or phenylmethyl; R 8 is C 1-6 alkyl, C 3-6 cycloalkyl phenyl or phenylmethyl; R 9 is cyano, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkyloxycarbonyl or aminocarbonyl; R 10 is hydrogen or C 1-6 alkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to disturbed fundic accomodation.

  本发明涉及式（I）化合物，其立体化学异构体，其N-氧化物形式或其药学上可接受的酸加成盐，其中-a1 = a2-a3 = a4-是一个双价基团，其中a1到a4中的一个或两个是氮，其余的a1到a4是-CH═; -Z1-Z2-是一个双价基团; -A-是一个式为-N（R6）-Alk2-的双价基团或含有一个或两个氮原子的5、6或7元饱和杂环; R1，R2和R3分别独立选择自氢，C1-6烷基，羟基，卤素等; Alk1和Alk2是可选取代的C1-6烷二基; R5是一个式为的基团，其中n为1或2; p1为0，p2为1或2; 或p1为1或2，p2为0; X是氧，硫或═NR9; Y2是氧或硫; R7是氢，C1-6烷基，C3-6环烷基，苯基或苯甲基; R8是C1-6烷基，C3-6环烷基苯基或苯甲基; R9是氰基，C1-6烷基，C3-6环烷基，C1-6烷氧羰基或氨基羰基; R10是氢或C1-6烷基; Q是一个双价基团。公开了制备所述产品的过程，包括所述产品的制剂及其作为药物的用途，特别是用于治疗与干扰胃底容纳有关的疾病。
• COMPOUNDS FOR TREATING IMPAIRED FUNDIC RELAXATION
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1296987B1

  公开（公告）日：2005-12-07
• INDOLE DERIVATIVES WITH AN IMPROVED ANTIPSYCHOTIC ACTIVITY
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1636239B1

  公开（公告）日：2007-07-18
• Novel indole derivatives with an improved antipsychotic activity
  申请人：Bartolome-Nebreda Manuel Jose

  公开号：US20070066608A1

  公开（公告）日：2007-03-22

  The present invention relates to a novel indol derivative according to Formula (I), a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables R 1, R 2 , R 3 , R 4 , R 5 , p, a 1 ═a 2 a 3 ═a 4 , Z 1 —Z 2 , X and Y are defined as in claim 1 . Said derivative exhibit a binding affinity towards dopamine receptors, in particular towards dopamine D 2 , D 3 and D 4 receptors, with selective serotonin reuptake inhibition properties and acting as 5-HT 1A agonists or partial agonists. The invention also relates to pharmaceutical compositions comprising the compounds according to the invention, the use thereof for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic disorders, most in particular schizophrenia and processes for their production.