N-Substituted Quinazolin- 2,4-diones as Adenosine Receptor Ligands

DOI:

https://doi.org/10.37285/ijpsn.2010.3.2.16

Authors

  • Shireesha B
  • G.V. Kumar
  • V M Reddy
  • Raghuprasad M
  • A R Rao

Abstract

Six new N-substituted quinazolinones were synthesized and evaluated for their adenosine antagonistic activity using allergic mice model where 1, 3-dibenzyl and 1, 3-dibutyl-quinazolindiones were found to be potent than 1, 3-dimethylanalogues. They were not significant in controlling the neutrophil and lymphocyte count but effective in controlling the eosinophil influx. In adenosine receptor binding studies, 1,3-dimethyl and 1,3-dibutyl derivatives were found to have significant adenosine A1 receptor binding efficiency with Ki values 9nM and 10nM, respectively, while 1,3- dibenzyl-quinazolinone was found to have significant binding to adenosine A2A receptor showing the influence of alkyl and aralkyl groups present in these compounds. Thus, the present work indicates the possibility to explore quinazolindiones as adenosine receptor ligands.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Keywords:

Adenosine ligands, N-alkyl quinazolin-diones, Allergic mice model, Radioligand binding studies

Downloads

Published

2010-08-31

How to Cite

1.
B S, Kumar G, Reddy VM, M R, Rao AR. N-Substituted Quinazolin- 2,4-diones as Adenosine Receptor Ligands. Scopus Indexed [Internet]. 2010 Aug. 31 [cited 2024 May 9];3(2):1015-21. Available from: https://www.ijpsnonline.com/index.php/ijpsn/article/view/509

Issue

Section

Research Articles

References

Alagarsamy V, Rupeshkumar M, Kavitha K, Meena S, Shankar D, Siddiqui AA, Rajesh R (2008) Synthesis and pharmacological investigation of novel 4-(2-methylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H1-antihistaminic agents, Eur. J. Med. Chem. 43: 2331-2337

Bahekar RH, Rao AR (2000) New bronchodilators-2: synthesis of 6-alkylbenzionidazo [1,2-C] quinazolines. Indian. J. Pharm. Sci. 62 (1): 41-45

Bahekar RH, Rao ARR (2001) Synthesis, evaluation and structure-activity relationships of 5-alkyl-2,3-dihydroimidazo [1,2-c] quinazoline, 2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-thiones and their oxo-analogues as new potential bronchodilators, Arzneim. Forsch. / Drug Res. 51 (4): 345-382

Baraldi PG, Aghazadeh M, Tabrizi A, Gessi S, Borea PA (2008) Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility. Chem Rev. 108 (1):238–263

Bogert MT, Gotthelf AH (1900) The direct synthesis of keto-dihydroquinazolins from orthoamino acids, J. Am. Chem. Soc. 22: 522-535

Cacciari B, Pastorin G, Bolcato C (2005) A2B adenosine receptor antagonists: recent developments, Mini Rev. Med. Chem. 5: 1053-1060

Carotti A, Cadavid MI, Centeno NB, Esteve C, Loza MI, Martinez A, Nieto R, Ravin E, Sanz F, Segarra V, Sotelo E, Stefanachi A, Vidal B (2006) Design, Synthesis and Structure activity relationships of 1,3,8 and 9- substituted -9-deaza xanthines at the human A2B adenosine receptor, J. Med. Chem. 49: 282-299

Daly JW (2007) Caffeine analogs: biomedical impact, Cell. Mol. Life Sci. 64: 2153-2169

El-Khamry AA, Shiba SA, Shalaby AA, Abd Alaha AA (2006) Synthesis of Some New Pyrazoloquinazolinone and Quinazolinone Derivatives, J. Heterocycl. Chem. 43: 1189-1193

Elzein E, Kalla R, Li X, Perry T, Parkhill E, Palle V, Varkhedkar V, Gimbel A, Zeng D, Lustig D, Leungc K, Zablocki J (2006) Novel 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as high affinity and selective A2B adenosine receptor antagonists, Bioorg. Med. Chem. Lett. 16: 302-306

Fan M, Mustafa SJ (2002) Adenosine-mediated bronchoconstriction and lung inflammation in an allergic mouse model, Pulm. Pharmacol. Ther. 15: 147-155

Fan M, Qin W, Mustafa SJ (2003) Characterization of adenosine receptors involved in adenosine-induced bronchoconstriction in an allergic mouse model, Am. J. Physiol. Lung Cell Mol. Physiol. 284: L1012- 1019

Gelfand EW, Joetham A, Cui JH, Balhorn A, Takeda K, Taube C, Dakhama A (2004) Induction and maintenance of airway responsiveness to allergen challenge are determined at the age of initial sensitization, J. Immunol. 173: 1298-1306

Holgate ST (2005) The quitiles prize lecture 2004, The identification of the adenosine A2B receptors as novel therapeutic target in asthma, Br. J. Pharmacol. 145: 1009-1015

Jacobson KA, Von LDKJE, Daly JW, Fredholm BB (1996) Adenosine receptor ligands: Differences with acute versus chronic treatment, Trends Pharmacol. Sci. 17: 108-113

Jindal DP, Bhatti RS, Ahlawat S, Gupta R (2002) Synthesis and bronchodilatory activity of some nitrogen bridgehead compounds, European. J. Med. Chem. 37 (5): 419-425

Kalla VR, Perry T, Elzein E, Varkedhkar V, Li X, Ibrahim P, Palle V, Xiao D, Jablocki J (2004) A2B adenosine receptor antagonists, US patent, 6825349

Kalla VR, Zablocki J (2009) Progress in the discovery of selective, high affinity A2B adenosine receptor antagonists as clinical candidates, Purinergic Signal. 5: 21-29

Moro S, Gao ZG, Jacobson KA, Spalluto G (2006) Progress in the pursuit of therapeutic adenosine receptor antagonists, Med. Res. Rev. 26 (2): 131-159

Muller CE (2003) Medicinal chemistry of adenosine A3 receptor ligands, Curr. Top. Med. Chem. 3: 445-462

Prasad MR, Rao ARR, Rao PS, Rajan KS, Meena S, Madhavi K (2008) Synthesis and adenosine receptor binding studies of some novel triazolothienopyrimidines, Eur. J. Med. Chem. 43 (3): 614-620

Rao ARR, Bahekar RH (1999) Synthesis of benzimidazo [1,2-c] quinazolines as possible bronchodilators, Indian. J. Chem. 38B (4): 434-439

Reisch J, Usifoh CO, Oluwadiya JO (1990) Acetylenic chemistry. XV : Reactions of 1,2,3,4-tetrahydro-2,4-dioxopyrido[2,3-d]pyrimidine with 3-bromoprop-1-yne, J. Heterocycl. Chem. 27 (2): 287-289

Stewart M, Steinig AG, Ma C, Song JP, Kibben BM, Castelhano AL, Lennan SJ (2004) [3H] OSIP339391, a selective, novel, and high affinity antagonist radioligand for adenosine A2B receptors, Biochem. Pharmacol. 68: 305-312

Sur S, Lam J, Bouchard P, Sigounas A, Holbert D, Metzger WJ (1996) Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses, J. Immunol. 157: 4173-4180

Thomas R, Webb DL (2003) Quinazolines as adenosine receptor antagonists: SAR and selectivity for A2B receptors, Bioorg. Med. Chem. 11(1): 77-85

Vidal B, Nueda A, Esteve C, Domenech T, Benito S, Reinoso RF, Pont M (2007) Discovery and characterization of 4-(2-furyl)-n-pyridin-3-yl-4,5-bipyrimidin-2-amine (LAS38096), a potent, selective, and efficacious A2B adenosine receptor antagonist, J.Med. Chem. 50: 2732-2736

Vidal JB, Trias CE (2005) Pyrimidin 2- amine derivatives and their use as A2B adenosine antagonist, E2229928, WO2005040155