Syntheses of N-(2-hexahydropyrimidinoethyl)propionanilides.

Theoretical Studies of the In-Solution Isomeric Protonation of Non-Aromatic Six-Member Rings with Two Nitrogens

“…4,11,12 Asymmetrically substituted six-member, saturated rings with two nitrogens are substructures in commercially available or potential drugs. The piperazine ring appears in antibacterial fluoroquinolone derivatives, 14 and analgesic effects have been documented for hexahydropyrimidines 15 (Scheme 1 (1,2)). In structure-based drug design it is important to find the hydrogen bond donor/acceptor sites for a potential drug in order to develop optimal interactions with the receptor.…”

Design, synthesis and nootropic activity of new analogues of sunifiram and sapunifiram, two potent cognition-enhancers

“…Commercially-available N-benzyl-homopiperazine 33 was treated with acetyl or propionyl chloride to give compound 36 and 37, which were hydrogenated to 42 and 43, and reacted with phenylacetyl, 4-fluorobenzenesulfonyl, benzoyl or isopropylsulfonyl chloride to give compounds 4-10. The same sequence of reactions was performed on N-benzyl-imidazolidine 34 and N-benzyl-hexahydropyrimidines 35 (prepared according to literature methods 17,18 ) and gave compounds 11-16 and 17-22, respectively. Treatment of N-propionylpiperazine 48 12 with phenyl chloroformiate, phenyl isocyanate or phenylacetyl chloride gave, respectively, the carbamate 23, urea 24 or amide 25.…”

“…doi:10.1016/j.bmc.2009.08.055 of action of these substances, we made further structural modifications on the lead molecules DM235 and MN19. Therefore, compounds 4-22 (Chart 1) were designed, in which (a) the piperazine cycle of DM235 has been expanded into a seven-membered ring (homopiperazines 4-10) or contracted into a five-membered ring (imidazolidines [11][12][13][14][15][16]; or (b) the amidic nitrogen atoms have been shifted from 1-4 into 1-3 position (hexahydropyrimidines [17][18][19][20][21][22]. To verify the importance of the presence and position of an aromatic ring, compounds 23-29 were designed, where the aromatic ring has been spaced from the carbonyl amide of DM235 by an oxygen (23) or a nitrogen (24) atom or by a methylene group (25), or where the aromatic benzoyl or p-fluorobenzenesulfonyl moieties have been replaced by a small acyl (acetyl or propionyl) group; the latter modification has been performed on both DM235, giving compounds 26 and 27, and on MN19, obtaining 28 and 29.…”