- Efficient copper-catalyzed synthesis of 2-amino-4(3h)-quinazolinone and 2-aminoquinazoline derivatives
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We have developed a versatile and efficient method for copper-catalyzed synthesis of both 2-amino-4(3H)-quinazolinone and 2-aminoquinazoline derivatives. The protocol uses readily available substituted 2-halobenzoic acids, 2-bromobenzaldehyde, 2-bromophen
- Huang, Xuhu,Yang, Haijun,Fu, Hua,Qiao, Renzhong,Zhao, Yufen
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experimental part
p. 2679 - 2688
(2010/01/21)
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- Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach
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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.
- 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
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experimental part
p. 7855 - 7865
(2009/12/07)
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- Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones
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A series of 2-sec-amino-3H-quinazolin-4-ones (4a-p) and 4-sec-amino-2-chloroquinazolines (5a-b) have been synthesized by nucleophilic substitution reaction of 2-chloro-4(3H)-quinazolones (3) and 2,4-dichloroquinazolines (2) with amines, respectively. Most of the synthesized compounds were evaluated for antihyperglycemic activity but only 4a,b,d,j,o displayed significant reduction in blood glucose level in streptozotocin and sucrose loaded rat models.
- Ram, Vishnu Ji,Farhanullah,Tripathi, Brajendra K.,Srivastava, Arvind K.
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p. 2439 - 2444
(2007/10/03)
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