Regioselective addition reactions at C-2 of 3,4-dihydropyrimidinones. Synthesis and evaluation of multifunctionalized tetrahydropyrimidines

Abstract

a b s t r a c tMultifunctionalized tetrahydropyrimidines derivatives have been synthesized from Biginelli 3,4-dihydropyrimidin-2-(1H)-thiones (DHPMs) efficiently. The transformation includes desulfurization of DHPMs with Raney-Ni and subsequent regioselective C-2 functionalization using a variety of C-nucleophiles with simultaneous activation with ethyl chloroformate. Functionalized pyrimidine derivatives containing bulky substituents at C-2 of the pyrimidine ring are cytostatic.

Synthesis of Pyrimidine, Dihydropyrimidinone, and Dihydroimidazole Derivatives under Free Solvent Conditions and Their Antibacterial Evaluation

“…This compound was obtained as bright crystals (ethyl alcohol), white color, yield 92%, mp 240 C; IR: cm À1 3200 (NH); 1 H NMR: (2E)-2-(1,3-Benzothiazol-2-ylimino)-6-methyl-2,3-dihydropyrimidine-4(1H)-one (5). This compound was obtained as powder (ethyl alcohol), buff color, 82% yield, mp 305 C; IR: cm À1 3303, 3184 (2NH), 1691 (CO); 1 H NMR: (2E)-2-(1,3-Benzothiazol-2-ylimino)-6-phenyl-2,3-dihydropyrimidine-4(1H)-one (6).…”

“…Although a large number of dihydropyrimidinone (DHPM) derivatives have been prepared in a single‐pot Biginelli multi‐component reaction and its variants , very useful and convincing structural variability of these interesting heterocycles have been achieved through chemical functionalization of all the six positions around the DHPM core . Recently, it was reported that the C‐2 amine substituted pyrimidine derivatives have inhibited Mycobacterium tuberculosis as well as their inhibitory effect against the proliferation of some cell cultures. In a continuation of our efforts to synthesize small molecule heterocyclic compounds from modified guanidines and active methylene compounds , we are reporting in this study the synthesis of C2‐amino/imino benzothiazole substituted dipyrimidines, dihydropyrimidinones, and dihydroimidazoles.…”

“…In view of wide spectrum biological activities such as anti‐allergic , antitumor , antipyretic, anti‐inflammatory , and antiparasitic activities exhibited by synthetic pyrimidine‐based scaffolds, a number of analogues have garnered considerable attention. During a screening effort for antiviral agents, it has been found that multifunctionalized tetrahydropyrimidines derivatives bearing bulky C‐2 alkyl substituents depict cytostatic activity and inhibit proliferation of murine leukemia, murine mammary carcinoma, human T‐lymphocyte, and human cervix carcinoma cells . The dihydropyrimidinones have recently emerged as important target molecules because of their therapeutic and pharmacological properties such as antiviral , antimitotic , anticarcinogenic , and antihypertensive and, noteworthy, as calcium channel modulators .…”

Facile transformation of Biginelli pyrimidin-2(1H)-ones to pyrimidines. In vitro evaluation as inhibitors of Mycobacterium tuberculosis and modulators of cytostatic activity

“…In view of wide spectrum biological activities such as anti allergic [2], antitumor [3], antipyretic [4], anti-inflammatory [4] and antiparasitic [5] activities, exhibited by synthetic pyrimidine based scaffolds, a number of analogues have garnered considerable attention. During a screening effort for antiviral agents, we found that multifunctionalized tetrahydropyrimidines derivatives bearing bulky C-2 alkyl substituents depict cytostatic activity and inhibit proliferation of murine leukemia, murine mammary carcinoma, human T-lymphocyte and human cervix carcinoma cells [6]. 3,4-Dihydropyrimidin-2-(1H)-ones (DHPMs) and their appropriately functionalized derivatives have interesting pharmacological profiles [7].…”

“…Although a large number of DHPM derivatives have been prepared in a single-pot Biginelli multi component reaction [8] (MCR) and its variants [9], very useful and convincing structural variability of these interesting heterocycles have been achieved through chemical functionalization of all the six positions around the DHPM core [10]. Recently, we reported [6] on the facile conversion of DHPMs into tetrahydropyrimidines. As part of an ongoing, multi-faceted program aimed toward development of small molecules as therapeutic agents, herein we report a straightforward conversion of Biginelli DHPMs into C-2 amine substituted pyrimidine derivatives and their screening as inhibitors of Mycobacterium tuberculosis and their inhibitory effect against the proliferation of some cell cultures.…”