Indoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 2: Asymmetric synthesis and biological evaluation

Mechanistic and Chiroptical Studies on the Desulfurization of Epidithiodioxopiperazines Reveal Universal Retention of Configuration at the Bridgehead Carbon Atoms

“…17 Diketopiperazine 12 was obtained by refluxing acylated indoline 11 with methylamine in THF/MeCN. 17 The sulfenylation of diketopiperazine 12 was performed using the method recently described by Nicolaou and co-workers 18,19 and afforded gliotoxin analogue (±)- 7 . The enantiomers were separated using semipreparative HPLC on a chiral stationary phase (see the Experimental Section for details).…”

Multitarget Drugs

“…Zhao et al tried to reproduce this exact ratio with the goal of obtaining D 4 affinity of less than 10 nM and D 2 affinity of less than 200 nM [24]. Introduction of a methyl group in the 2-position of the indoline ring gave an improvement in D 2 activity, 13, and also good selectivity against a diverse range of other targets including alpha-1 [25]. Introduction of a methyl group in the 2-position of the indoline ring gave an improvement in D 2 activity, 13, and also good selectivity against a diverse range of other targets including alpha-1 [25].…”

1,4-Bis[(Z)-2-(3-mesityl-3-methylcyclobutyl)-2-(thiosemicarbazono)ethyl]piperazine dimethyl sulfoxide disolvate

“…The molecule of the title compound, (I), contains two thsc groups, one piperazine ring and two cyclobutyl rings. Some piperazine-containing derivatives constitute a novel class of mixed D2/D4 receptor antagonists (Zhao et al, 2002), and N,N 0 -disubstitued piperazine derivatives are antifilarial, antiamoebic and spermicidal agents (Yogavel et al, 2003;Sonurlikar et al, 1977).…”