2-[[3-[3-[(dimethylamino)methyl]phenoxy]propyl]amino]-5-[(3-pyridinyl)methyl]-4(3H)-pyrimidinone

• 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: 2-[[3-[3-[(dimethylamino)methyl]phenoxy]propyl]amino]-5-[(3-pyridinyl)methyl]-4(3H)-pyrimidinone
• 英文别名: 2-[[3-[3-[(Dimethylamino)methyl]phenoxy]propyl]amino]-5-(3-pyridinyl)methyl-4 (3H)-pyrimidinone；2-[3-[3-[(dimethylamino)methyl]phenoxy]propylamino]-5-(pyridin-3-ylmethyl)-1H-pyrimidin-6-one
• 化学式: C₂₂H₂₇N₅O₂
• 分子量: 393.489
• InChiKey: AOGRKVZOCDKOQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  78.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-(吡啶-3-基甲基)-2-甲硫基-4-嘧啶酮 、 3-(3-aminopropoxy)-N,N-dimethylbenzenemethanamine 在 silica methanol 作用下， 反应 16.0h， 以The residue, after column chromatography (silica/methanol -0.88 ammonia, 79:1) gave the title compound as a yellow gum (0.96 g)的产率得到2-[[3-[3-[(dimethylamino)methyl]phenoxy]propyl]amino]-5-[(3-pyridinyl)methyl]-4(3H)-pyrimidinone
  参考文献：
  名称：

  Pyrimidone derivatives

  摘要：

  式(I)的化合物如下：##STR1## 其中，R.sub.1和R.sub.2均可代表氢、烷基、环烷基、烯基、炔基、芳基烷基或烷基，被羟基、C.sub.1-3烷氧基、氨基、C.sub.1-3烷基氨基或双C.sub.1-3烷基氨基取代，或者R.sub.1和R.sub.2与它们所连接的氮原子一起形成一个脂环杂环，该脂环杂环可以是未取代的，也可以被一个或多个C.sub.1-3烷基基团或一个羟基基团取代，并且可能含有另一个杂原子。Alk是一条直链下游烷基链，Q是呋喃或噻吩环，呋喃环可选地带有进一步的取代基R.sub.5，该取代基R.sub.5相邻于基团R.sub.1 R.sub.2 NAlk--或Q代表苯环。R.sub.5代表卤素或C.sub.1-3烷基，它可以被羟基或C.sub.1-3烷氧基取代；X代表--CH.sub.2 --、--O--或--S--；n代表零或1；m代表2、3或4；Y代表.dbd.O或.dbd.S；R.sub.3代表氢，此时R.sub.4代表甲基，或者R.sub.3代表--(CH.sub.2).sub.p V(CH.sub.2).sub.q Ar、苯基或烷基，此时R.sub.4代表氢；V代表--CH.sub.2 --、--O--或--S--；p代表零、1、2或3；q代表零、1、2或3；p+q的总和不超过3；Ar代表一个芳香碳环或杂环，可以选配至少一个C.sub.1-3烷基、C.sub.1-3烷氧基、C.sub.1-3烷基、羟基、C.sub.1-3烷氧基、亚甲二氧基、卤素、三氟甲基或双C.sub.1-3烷基氨基基团；但当n为零且X为氧时，则Q代表苯环或噻吩环。式(I)的化合物具有作为选择性组织胺H.sub.2-拮抗剂的药理活性。

  公开号：

  US04524071A1

文献信息

• Pyrimidinone derivatives, processes for preparing them and pharmaceutical compositions containing them
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0013071A1

  公开（公告）日：1980-07-09

  The invention provides new histamine H2- antagonist compounds of Structure 1 in which R' is hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen, trifluoromethyl, nitro, amino, lower alkylamino, lower alkanoylamino, di(lower alkyl)amino or cyano; R2 is in the 3-, 4- or 5- position and is hydrogen, or R2 is lower alkyl substituted by amino, lower alkylamino, di(lower alkyl)amino, N-piperidino or N-pyrollidino, or R2 is ethoxy or propoxy w-substituted by amino, lower alkylamino, di(lower alkyl)amino, N-piperidino or N-pyrollidino; Y is methylene or oxygen and X is methylene or sulphur provided that one or two of the groups X and Y is methylene; Z is hydrogen or lower alkyl; A is C1-C5 alkylene or-(CH2)pW-(CH2)q-where W is oxygen or sulphur and p and q are such that their sum is from 1 to4, and B is hydrogen, methyl, C3-C6 cycloalkyl, a heteroaryl group optionally substituted by one or more of the groups lower alkyl, lower alkoxy, halo, hydroxy and amino, or B is a naphthyl, 6-(2,3-dihydro-1,4-benzodioxinyl), a 4- or 5-(1,3-benzodioxolyl) group, or a phenyl group optionally substituted with one or more lower alkyl, lower alkoxy, halogen, aryl(lower alkoxy), hydroxy, lower alkoxy-lower alkoxy, trifluoromethyl, di(lower alkyl)amino, phenoxy, halophenoxy, lower alkoxyphenoxy, phenyl, halophenyl or lower alkoxyphenyl groups and pharmaceutical compositions containing them. A compound of Structure 1 can be prepared by reacting a compound of Structure 3 in which Q is nitroamino, loweralkylthio, benzylthio or halogen with an amine of Structure 2, in which R3 is in the 3-, 4- or 5p position and is hydrogen, lower alkyl substituted by a group R4, or is R4CH2CH2O-or R4CH2CH2CH2O-, where R' is di(lower alkyl)amino, N-piperidino, N-pyrrollidino, a protected amino group or a protected lower alkylamino group, and where necessary any amino-protecting group present in the substituent R3 is removed.

  本发明提供了结构 1 的新型组胺 H2- 拮抗剂化合物 其中R'是氢、低级烷基、低级烷氧基、羟基、卤素、三氟甲基、硝基、氨基、低级烷基氨基、低级烷酰氨基、二（低级烷基）氨基或氰基；R2 位于 3-、4-或 5-位且为氢，或 R2 为被氨基、低级烷基氨基、二（低级烷基）氨基、N-哌啶基或 N-吡咯烷基取代的低级烷基，或 R2 为被氨基、低级烷基氨基、二（低级烷基）氨基、N-哌啶基或 N-吡咯烷基取代的乙氧基或丙氧基；Y 为亚甲基或氧，X 为亚甲基或硫，条件是 X 和 Y 中的一个或两个基团为亚甲基；Z 为氢或低级烷基；A是C1-C5亚烷基或-(CH2)pW-(CH2)q-其中W是氧或硫，p和q的和为1至4，B是氢、甲基、C3-C6环烷基、任选被一个或多个基团低级烷基、低级烷氧基、卤代、羟基和氨基取代的杂芳基，或者B是萘基、6-(2,3-二氢-1,4-苯并二噁烷基)、4-或5-(1、3-苯并二恶茂基）基团，或任选被一个或多个低级烷基、低级烷氧基、卤素、芳基（低级烷氧基）、羟基、低级烷氧基-低级烷氧基、三氟甲基、二（低级烷基）氨基、苯氧基、卤代苯氧基、低级烷氧基苯氧基、苯基、卤代苯基或低级烷氧基苯基基团取代的苯基基团以及含有它们的药物组合物。结构 1 的化合物可通过结构 3 的化合物（其中 Q 为硝基氨基、低级烷硫基、苄硫基或卤素） 与结构 2 的胺反应制备，其中 R3 位于 3-、4-或 5p 位，是氢、被基团 R4 取代的低级烷基或 R4CH2CH2O- 或 R4CH2CH2CH2O-，其中 R' 是二（低级烷基）氨基、N-哌啶基、N-吡咯烷基、受保护的氨基或受保护的低级烷基氨基，必要时去除取代基 R3 中存在的任何氨基保护基。
• US4496567A
  申请人：——

  公开号：US4496567A

  公开（公告）日：1985-01-29
• US4524071A
  申请人：——

  公开号：US4524071A

  公开（公告）日：1985-06-18
• [EN] NEW HISTAMINE H2-ANTAGONISTS
  申请人：——

  公开号：WO1980000966A1

  公开（公告）日：1980-05-15

  (EN) New histamine H2-antagonist compounds of structure 1 (FORMULA) in which R1 is hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen trifluoromethyl, nitro, amino, lower alkylamino, lower alkanoylamino, di (lower alkyl) amino or cyano; R2 is in the 3-, 4- or 5-position and is hydrogen, R2 is lower alkyl substituted by amino, lower alkylamino, di (lower alkyl) amino, N-piperidino or N-pyrollidino, or R2 is ethoxy or propoxy (Alpha)-substituted by amino, lower alkylamino, di (lower alkyl) amino, N-piperidino or N-pyrollidino; Y is methylene or oxygen and X is methylene or sulphur provided that one or two of the groups X and Y is methylene; Z is hydrogen or lower alkyl; A is C1-C5 alkylene or -(CH2)pW-(CH2)q where W is oxygen or sulphur and p and q are such that their sum is from 1 to 4, and B is hydrogen methyl, C3-C6 cycloalkyl, a heteroaryl group optionally substituted by one or more of the groups lower alkyl, lower alkoxy, halo, hydroxy and amino, or B is naphthyl, 6-(2,3-dihydro-1,4-benzodioxinyl), a4- or 5-(1,3-benzodioxolyl) group, or a phenyl group optionally substituted with one or more lower alkyl, lower alkoxy, halogen, aryl (lower alkoxy), hydroxy, lower alkoxy-lower alkoxy, trifluoromethyl, di (lower alkyl) amino, phenoxy, halophenoxy, lower alkoxyphenoxy, phenyl, halophenyl or lower alkoxyphenyl groups and pharmaceutical compositions containing them. A compound of structure 1 can be prepared by reacting a compound of structure 3 in which Q is nitroamino, loweralkylthio, benzylthio or halogen with an amine of structure 2, in which (FORMULA) R3 is in the 3-, 4- or 5-position and is hydrogen, lower alkyl substituted by a group R4, or is R4CH2CH2O-or R4CH2CH2CH2O-, where R4 is di(lower alkyl)amino, N-piperidino, N-pyrrollidino, a protected amino group or a protected lower alkylamino group, and where necessary any amino-protecting group present in the substituent R3 is removed. (FR) Nouveaux composes antagonistes des recepteurs-H2 de l"histamine, de structure 1 (FORMULE) dans laquelle R1 represente l"hydrogene, un groupe alkyle inferieur, alkoxy inferieur, hydroxy, halogene, trifluoromethyle, nitro, amino, alkylamino inferieur alcanoylamino inferieur, di(alkyle inferieur) aminoe ou cyano; R2 se trouve en position 3-, 4-, ou 5- et represente l"hydrogene ou R2 represente un groupe alkyle inferieur substitue par amino, alkylamino inferieur, di(alkyle inferieur) amino, N-piperidino ou N-pyrrolidino, ou R2 represente un groupe ethoxy ou propoxy (Alpha)-substitue par amino, alkylamino inferieur, di(alkyle inferieur) amino, N-piperidino ou N-pyrrolidino; Y represente un groupe methylene ou l"oxygene et X represente un methylene; Z represente l"hydrogene ou un groupe alkyle inferieur; A represente un groupe alkylene en C1-C5 ou -(CH2)pW-(CH2)q dans lequel W represente l"oxygene ou le soufre et p et q sont tels que leur somme est de 1 a 4, et B represente l"hydrogene, un groupe methyle, cycloalkyle en C3-C6, un groupe heteroaryle facultativement substitue par un ou plus des groupes alkyle inferieurs, alkoxy inferieurs, halo, hydroxy et amino ou B represente un groupe naphtyle, 6-(2,3-dihydro-1,4-benzodioxinyl), un groupe 4- ou 5-(1,3-benzodioxolyl) ou un groupe phenyle facultativement substitue par un ou plus d"un groupe alkyle inferieur, alkoxy inferieur, halogene, aryl (alkoxy inferieur), hydroxy, alkoxy inferieur-alkoxy inferieur, trifluoromethyl, di(alkyle inferieur) amino, phenoxy, halophenoxy, alkoxy inferieur phenoxy, phenyle, alophenyl ou groupes alkoxy inferieur phenyle et les compositions pharmaceutiques les contenant. Un compose de structure 1 peut etre prepare en faisant reagir un compose de structure 3 dans laquelle Q represente un groupe nitroamino, thio-alkyle inferieur, benzylthio ou un halogene avec une amine de structure 2 dans laquelle (FORMULE) R3 est en position 3-, 4- ou 5- et represente l"hydrogene, un groupe alkyl inferieur substitue par un groupe R4 ou represente un groupe R4CH2CH2O- ou R4CH2CH2CH2O- dans lequel R4 represente un groupe di(alkyle inferieur) amino, N-piperidino, N-pyrrolidino, un groupe amino protege ou un groupe akylamino inferieur protege et si necessaire, tout groupe protecteur de groupe amine present dans le substituent R3 est elimine.
• Pyrimidone derivatives
  申请人：Glaxo Group Limited

  公开号：US04524071A1

  公开（公告）日：1985-06-18

  Compounds of the formula (I) ##STR1## in which R.sub.1 and R.sub.2 each may represent hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, or alkyl, substituted by hydroxy, C.sub.1-3 alkoxy, amino, C.sub.1-3 alkylamino or di-C.sub.1-3 alkylamino or R.sub.1 and R.sub.2 together with the nitrogen atom to which they are attached form an alicyclic heterocyclic ring which may be unsubstituted or may be substituted by one or more C.sub.1-3 alkyl groups or a hydroxy group and/or may contain another heteroatom are described. Alk is a straight lower alkylene chain, Q is a furan or thiophen ring, the furan ring optionally bearing a further substituent R.sub.5 adjacent to the group R.sub.1 R.sub.2 NAlk-- or Q represents a benzene ring. R.sub.5 represents halogen or C.sub.1-3 alkyl which may be substituted by a hydroxy or C.sub.1-3 alkoxy group; X represents --CH.sub.2 --, --O-- or --S--; n represents zero or 1; m represents 2, 3 or 4; Y represents .dbd.O or .dbd.S; R.sub.3 represents hydrogen in which case R.sub.4 represents methyl or R.sub.3 represents --(CH.sub.2).sub.p V(CH.sub.2).sub.q Ar, phenyl, or alkyl in which case R.sub.4 represents hydrogen; V represents --CH.sub.2 --, --O--, or --S--; p represents zero, 1, 2 or 3; q represents zero, 1, 2 or 3; the sum of p+q being 3 or less; Ar represents an aromatic carbocyclic or heterocyclic ring being optionally substituted by at least one C.sub.1-3 alkyl, C.sub.1-3 alkoxy C.sub.1-3 alkyl, hydroxy, C.sub.1-3 alkoxy, methylenedioxy, halogen, trifluoromethyl or di-C.sub.1-3 alkylamino group; except that when n is zero and X is oxygen then Q represents a benzene or thiophen ring. The compounds of formula (I) have pharmacological activity as selective histamine H.sub.2 -antagonists.

  化合物的结构式为（I）##STR1##其中R.sub.1和R.sub.2可以分别表示氢、烷基、环烷基、烯基、炔基、芳基烷基或烷基，其上取代基可能是羟基、C.sub.1-3烷氧基、氨基、C.sub.1-3烷基氨基或二C.sub.1-3烷基氨基，或者R.sub.1和R.sub.2与它们连接的氮原子一起形成一个脂环杂环，该杂环可能未取代或者可能被一个或多个C.sub.1-3烷基或一个羟基取代，和/或可能包含另一个杂原子。Alk是一条直链较低的烷基链，Q是呋喃或噻吩环，呋喃环可选地带有进一步的取代基R.sub.5，与基团R.sub.1 R.sub.2 NAlk--相邻，或Q代表苯环。R.sub.5代表卤素或C.sub.1-3烷基，可能被一个羟基或C.sub.1-3烷氧基取代；X代表--CH.sub.2--、--O--或--S--；n表示零或1；m表示2、3或4；Y表示.dbd.O或.dbd.S；R.sub.3表示氢，此时R.sub.4表示甲基，或者R.sub.3表示--(CH.sub.2).sub.p V(CH.sub.2).sub.q Ar、苯基或烷基，此时R.sub.4表示氢；V表示--CH.sub.2--、--O--或--S--；p表示零、1、2或3；q表示零、1、2或3；p+q的总和为3或更少；Ar表示一种芳香环或杂环，可选择地被至少一个C.sub.1-3烷基、C.sub.1-3烷氧基、羟基、C.sub.1-3烷氧基、亚甲二氧基、卤素、三氟甲基或二C.sub.1-3烷基氨基基团取代；但当n为零且X为氧时，则Q代表苯环或噻吩环。式（I）的化合物具有作为选择性组织胺H.sub.2 -拮抗剂的药理活性。