150450-96-7Relevant academic research and scientific papers
Discovery of potent cyclic GMP phosphodiesterase inhibitors. 2-Pyridyl- and 2-imidazolylquinazolines possessing cyclic GMP phosphodiesterase and thromboxane synthesis inhibitory activities
Lee,Konishi,Yu,Miskowski,Riviello,Macina,Frierson,Kondo,Sugitani,Sircar,Blazejewski
, p. 3547 - 3557 (1995)
Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2- phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP- PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3- pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.
Design, synthesis, and structure-activity relationships of highly potent 5-HT3 receptor ligands
Verheij, Mark H. P.,Thompson, Andrew J.,Van Muijlwijk-Koezen, Jacqueline E.,Lummis, Sarah C. R.,Leurs, Rob,De Esch, Iwan J. P.
, p. 8603 - 8614 (2013/01/15)
The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3R hit fragment. Here we describe the synthesis and structure-activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT3R affinity using a [3H]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pKi > 10) for the 5-HT3 receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT3 ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches.
USE OF COMPOUNDS FOR PREPARING ANTI-TUBERCULOSIS AGENTS
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Page/Page column 13, (2010/12/29)
Compounds of a compound of compound of general formula (I) wherein X1, X2, A, R1R2, R3 and R4 are as defined herein; are useful as anti-mycobacterial agents, especially agents for the treatment of tuberculosis.
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; experimental part, 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.
Method of treating a patient having a precancerous lesions with amide quinazoline derivatives
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, (2008/06/13)
Derivatives of quinazoline are useful for the treatment of patients having precancerous lesions. These compounds are also useful to inhibit the growth of neoplastic cells.
Anti-ischemic 2,4-diaminoquinazolines
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, (2008/06/13)
The invention is directed to certain 2,4-diaminoquinazoline compounds, their pharmaceutically acceptable salts, the pharmaceutical compositions comprising those compounds and their therapeutic methods of use. The compounds possess anti-ischemic activity.
4-aminoquinazoline derivatives
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, (2008/06/13)
The compounds of the formula: STR1 wherein R1, Y, A, R4, n, Z, CyB, R3, and m are defined in the specification.
