Lehmann J, Schulze G, Radwansky A
Pharmazeutisches Institut, Universität Bonn.
Arch Pharm (Weinheim). 1993 May;326(5):291-6. doi: 10.1002/ardp.19933260508.
Addition of piperidines 15a-d to methylene lactones 8,14a gives the "gamma-lactonized" diphenylbutylpiperidine-type neuroleptics 3a,b,d,4a-d. 8 can be produced by cyclization or--as well as 14--from the corresponding alpha-carboxylactone. 1H- and 13C-nmr data give evidence for the equatorial position of the aminomethyl group in all derivatives of 3 and 4 and bisequatorial-trans-configuration in 4a-d. 3H-spiroperidole displacement at the D2 receptor in rat brain by 3,4 and the "gamma-lactonized" butyrophenone neuroleptics 1,2a-c was investigated. Some compounds show moderate up to high (3b) activity.
将哌啶类化合物15a - d添加到亚甲基内酯8、14a中，可得到“γ - 内酯化”的二苯基丁基哌啶类抗精神病药物3a、b、d、4a - d。8可通过环化反应制得，或者与14一样，由相应的α - 羧基内酯制得。1H和13C核磁共振数据表明，在3和4的所有衍生物中，氨基甲基处于赤道位置，在4a - d中为双赤道反式构型。研究了3、4以及“γ - 内酯化”的丁酰苯类抗精神病药物1、2a - c对大鼠脑内D2受体的3H - 螺哌啶置换作用。一些化合物表现出中等至高（3b）活性。
