A novel 3,4-dihydropyrimidin-2(1H)-one: HIV-1 replication inhibitors with improved metabolic stability

An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors

“…13 We were intrigued by the physical similarity between our DHPM derivatives and the related structures 2 , which were described to possess inhibitory activity toward HIV replication in cells, although no MOA has been reported. 13 We therefore designed a biological testing funnel to narrow down the target of the DHPMs (Fig. 2).…”

“…11,12 A comprehensive analysis of published bioactivities of DHPMs with some similarity to our derivatives led us to investigate activity against human immunodeficiency virus (HIV), 13 a therapeutic target that is amenable to phenotypic screening. HIV is the causative agent of acquired immunodeficiency syndrome (AIDS), a disease for which there is no cure.…”

Transformations of Di‐ and Tetrahydropyrimidine Derivatives into Condensed Heterocycles with Retention of their Partially Saturated Structure

“…For example, approach, which is based on bromination and a subsequent nucleophilic replacement reaction, is well documented. 6‐Bromo‐ and 6‐dibromomethyl‐3,4‐dihydropyrimidines are a versatile, readily accessible building blocks for the synthesis of furo[3,4‐ d ]pyrimidines , pyrrolo[3,4‐ d ]pyrimidines , pyrimido[4,5‐ d ]pyridazines , thiazolo[3,4‐ c ]pyrimidine , and cyclopenta[d]pyrimidine .…”

Synthesis of pyrimidine carboxamide derivatives catalyzed by uranyl nitrate hexa Hydrate with their antibacterial and antioxidant studies

“…Biginelli reaction takes place by mixing different substituted aldehydes, urea or thiourea, and an active 1,3-dicarbonyl compound in combination with different catalytic systems such as AcOH [14], ZrCl 4 [15], Cu(OTf) 2 [16], SiO 2 /H 2 SO 4 [17], La(OTf) 3 [18], CdCl 2 [19], 1-n-butyl-3-methyl imidazolium tetrafluoroborate [20], SiO 2 /NaHSO 4 [21], Pb(NO 3 ) 2 [22], NaCl [23], KSF clay [24], FeCl 3 [25], BiCl 3 [26], ion-exchange resin [27], LiBr [28] [32], Mn(OAc) 3 [33], InBr 3 [ 34], microwave [35][36][37][38] or ultrasound irradiation [39] and solvent-free conditions [40], Co(NO 3 ) 2 .6H 2 O [41], ZnCl 2 /TBAB [42]. In the last two decades microwave mediated reactions have been of great interest in organic synthesis because of their shorter reaction times and high yields of products with good selectivity.…”

“…The limited availability of the natural products renders them to be attractive targets for total synthesis [3]. The dihydropyrimidinone (DHPM) is the most important core structure in the synthesis of different medicinally and pharmacologically valuable agents such as antibacterial [4], antiviral [5], antitumor [6], antihypertensive agents [7], calcium channel blockers [8], neuropeptide Y (NPY) antagonists [9], α-1a-antagonists [10] and anti-inflammatory drugs [11].…”