958791-80-5Relevant articles and documents
Quinazolinediones and quinazolinethiones by intramolecular ester amidation
Ahmed, Ejaz,Manwar, Muhammad Ramzan,Sharif, Ahsan,Mukhtar-Ul-Hassan,Ahmed, Neman,Malik, Abdul,Mahmood, Zaid,Munawar, Munawar Ali
experimental part, p. 417 - 420 (2012/04/04)
A new synthetic route was devised for synthesis of Quinazoline-2,4(1H,3H)- dione 5 in which salicylic acid 1 was treated with urea 2 to afford urea arylated ortho-urahydroxy benzoic acid 4. Ortho-urahydroxy benzoic acid 4 is the intermediate moiety which upon cyclization corroborated the cyclic formation of 2, 4-quinazolinedione 5. To form the quinazoline derivative 2, 3-dihydro-2-thioxoquinazolin-4(1H)-one 5a thiourea 3 is used in place of urea 2. Thiourahydroxy benzoic acid 4a is another intermediate compound formed by reacting salicylic acid 1 with thiourea 3. Thiourahydroxy benzoic acid 4a upon interamolecular ester amidation gave final product 2, 3-dihydro-2- thioxoquinazolin-4(1H)-one 5a. This new method replaces the isocyanates and cyanides usage for the formation of quinazolinediones because the incorporation of isocyanates and cyanides is extremely poisonous and cause fatal diseases and immediate death upon contact.
Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach
Smits, Rogier A.,De Esch, Iwan J. P.,Zuiderveld, Obbe P.,Broeker, Joachim,Sansuk, Kamonchanok,Guaita, Elena,Coruzzi, Gabriella,Adami, Maristella,Haaksma, Eric,Leurs, Rob
supporting information; scheme or table, p. 7855 - 7865 (2009/12/07)
From a series of small fragments that was designed to probe the histamine H4 receptor (H4R), we previously described quinoxaline-containing fragments that were grown into high affinity H 4R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H4R compounds. This approach led to the discovery of 6-chloro-N-(furan-3-ylmethyl)2-(4-methylpiperazin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl) quinazolin-4-amine (VUF10497, 55) as potent human H4R inverse agonists (pKi ) 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine H 1 receptor (H1R) and therefore represent a novel class of dual action H1R/H4R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quinazolines are antagonists at the rat H4R and were found to possess anti-inflammatory properties in vivo in the rat.
