Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of HAT

A Series of 2,4(1H,3H)-Quinazolinedione Derivatives: Synthesis and Biological Evaluation as Potential Anticancer Agents

“…Compound 6 (0.280 g, 1 mmol) and 1-(diphenylmethyl) piperazine (0.252 g, 1 mmol) were reacted according to the general procedure for compounds 7-34 and the crude product was crystallized from methanol-ether mixture to give white powdered crystalline compound; mp: 262.4°C, yield: 21 mg 6,7-Dimethoxy-3-{2-[4-(4-methoxyphenyl)piperazin-1yl]-2-oxoethyl}quinazoline-2,4(1H,3H)-dione (32). Compound 6 (0.280 g, 1 mmol) and 1-(4-methoxyphenyl) piperazine (0.192 g, 1 mmol) were reacted according to the general procedure for compounds 7-34 and the crude product was washed with hot acetonitrile and methanol to give white powdered crystalline compound; mp: 283.5 °C, yield: 120 mg (26% xyquinazoline-2,4(1H,3H)-dione (33). Compound 6 (0.280 g, 1 mmol) and 1-benzoylpiperazine (0.190 g, 1 mmol) were reacted according to the general procedure for compounds 7-34 and the crude product was crystallized from methanolether mixture to give white powdered crystalline compound; mp: 168.5 °C, yield: 32 mg (7%).…”

“…Various literatures report numerous 2,4(1H,3H)quinazolinedione analogues showing a wide variety of biological activities such as anticancer [7][8][9][10][11][12][13][14][15][16][17][18][19][20], antimicrobial [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], antihypertensive [38][39][40], anticonvulsant [41][42][43][44][45][46][47][48][49], anti-inflammatory [50], 5-hydroxytryptamine 3 (5-HT 3 ) receptor antagonist [51], phosphodiesterase (PDE) 4 inhibition [52,53], calcium-independent phosphodiesterase enzyme inhibition (CaIPDE) [54], cyclin-dependent kinase 5 (CDK5) inhibition…”

Phytochemical and antitrypanosomal investigation of the fractions and compounds isolated fromArtemisia elegantissima

“…The method was followed as detailed in Clark et al (2012). Unless otherwise stated, chemicals and solvents were of reagent or anhydrous grade and used as obtained from commercial sources without further purification.…”

Synthesis and biological evaluation of N -cyanoalkyl-, N -aminoalkyl-, and N -guanidinoalkyl-substituted 4-aminoquinoline derivatives as potent, selective, brain permeable antitrypanosomal agents

“…Chemotherapy is therefore of particular importance 8 . Unfortunately, the few drugs that have been approved for HAT (pentamidine and suramin for early stage HAT; melarsoprol and eflornithine, alone or in combination with nifurtimox, for late stage HAT) are unsatisfactory for several reasons, which include the occurrence of major side effects, high costs associated with parenteral administration and medical supervision, lack of brain permeability (in the case of pentamidine and suramin), which precludes their use in late stage HAT, and the increasing emergence of resistance 9, 10, 11. Thus, the development of novel antitrypanosomal compounds that can overcome these issues is urgently needed 3, 12…”