论文部分内容阅读
组胺对血管的效应与组胺H_1和H_2受体有关。为了抑制组胺对血管的舒张和降压效应,要求组胺拮抗剂对二种受体同时具有阻断作用,曾应用奥美替丁(Oxmetidine)进行组胺H_1受体拮抗剂的构效研究,它也有一些H1受体拮抗活性,以-CH_2-取代-S-,并用取代的嘧啶环代替咪唑和次甲二氧苯基环,希望在增强对H_1受体的拮抗活性时,仍能保留对H_2受体的拮抗活性。当吡啶环上的取代基为甲氧基时(如SK&F-93319),体外测得的抑制二种受体的活性强度相似。合成在回流的四氢呋喃中,2-氯-3-硝基吡啶(Ⅰ)与二乙基2-(2-氰乙基)丙二酸(Ⅱ)借助NaH缩合成1-氰基-3,3-双(乙氧基羰基)-3-(3-硝基-2-吡啶基)丙烷(Ⅲ),
The effect of histamine on blood vessels is related to histamine H 1 and H 2 receptors. In order to inhibit histamine on vascular relaxation and antihypertensive effect, histamine antagonists are required to block both receptors at the same time, have been used Ometidine (Oxmetidine) histamine H 1 receptor antagonist structure-activity studies , It also has some H1 receptor antagonistic activity, replacing -S- with -CH2- and substituting substituted pyrimidine ring for imidazole and methyldioxyphenyl ring, hoping to retain the antagonist activity on H_1 receptor Antagonist activity on H 2 receptor. When the substituent on the pyridine ring is methoxy (eg SK & F-93319), the activity of the two receptors tested in vitro is similar in activity. Synthesis of 2-chloro-3-nitropyridine (I) and diethyl 2- (2-cyanoethyl) malonic acid (II) were condensed by condensation with NaH to 1-cyano-3,3 Bis (ethoxycarbonyl) -3- (3-nitro-2-pyridyl) propane (III)