scholarly journals Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Siew Lee Cheong ◽  
Gopalakrishnan Venkatesan ◽  
Priyankar Paira ◽  
Ramasamy Jothibasu ◽  
Alexander Laurence Mandel ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Rational Design ◽  
Receptor Subtypes ◽  
Receptor Antagonists ◽  
Design And Optimization ◽  
The Past ◽  
Chemistry Research ◽  
Pathological Conditions ◽  
Structure Activity ◽  
Selective Antagonists

In the past few decades, medicinal chemistry research towards potent and selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3) has been evolving rapidly. These antagonists are deemed therapeutically beneficial in several pathological conditions including neurological and renal disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of compounds have been successfully synthesized and identified as potent human adenosine receptor antagonists. In this paper, an overview of the structure-activity relationship (SAR) profiles of promising nonxanthine pyrazolo derivatives is reported and discussed. We have emphasized the SAR for some representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3-d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This overview not only clarifies the structural requirements deemed essential for affinity towards individual adenosine receptor subtypes, but it also sheds light on the rational design and optimization of existing structural templates to allow us to conceive new, more potent adenosine receptor antagonists.

scholarly journals Structure activity relationship of 2-arylalkynyl-adenine derivatives as human A3 adenosine receptor antagonists

MedChemComm ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 1920-1932 ◽  
Author(s):  
Jinha Yu ◽  
Philip Mannes ◽  
Young-Hwan Jung ◽  
Antonella Ciancetta ◽  
Amelia Bitant ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Receptor Antagonists ◽  
Agonist Affinity ◽  
Structure Activity ◽  
Selective Antagonists ◽  
A3 Adenosine Receptor ◽  
Relationship Of ◽  
Adenine Derivatives

Adenines that incorporate known agonist affinity-enhancing substituents are A3AR-selective antagonists.

scholarly journals Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

2013 ◽  
Vol 82 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Jan Gnus ◽  
Albert Czerski ◽  
Stanisław Ferenc ◽  
Wojciech Zawadzki ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Abdominal Aorta ◽  
Adrenergic Receptor ◽  
Receptor Subtypes ◽  
Organ Bath ◽  
Dependent Manner ◽  
Receptor Antagonists ◽  
Selective Antagonists

Investigation of the effect of α1-adrenergic receptor subtypes on the contraction of the abdominal aorta will allow for more effective treatment of hypertension by use of selective antagonists. The aim of the study was to evaluate the participation of α1-adrenergic receptor subtypes in the contractility of the aortic smooth muscle cells in rabbits. The in vitro experiments were performed in isolated tissue preparations from 30 adult female New Zealand rabbits. The abdominal aortic sections were placed in organ bath chambers and contracted with increasing doses of non-selective α1-adrenergic receptor agonist phenylephrine without pre-incubation or after incubation in α1-adrenergic receptor subtype-selective or non-selective antagonists. Separate sections were incubated with increasing concentrations of antagonists. Phenylephrine caused maximal rise in arterial smooth muscle tone to 4.75 ± 0.47 mN. The most potent in blocking phenylephrine induced contraction was 5-metylurapidil (α1A-adrenergic receptor antagonist) followed by phentolamine and prazosin (non-selective α1-adrenergic receptor antagonists); BMY 7378 (α1D-adrenergic receptor antagonist), cyclazosin and L-765.314 (α1B-adrenergic receptor antagonists) were less effective. All antagonists, except BMY 7378 elicited relaxation of non-precontracted aorta in dose dependent manner. Our results indicate that postsynaptic α1A receptors are the most potent in producing rabbit abdominal aorta contraction, while α1B and α1D subtypes are less effective.

scholarly journals Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists: A complete structure–activity profile

2006 ◽  
Vol 3 (3) ◽  
pp. 183-193 ◽  
Author(s):  
Barbara Cacciari ◽  
Chiara Bolcato ◽  
Giampiero Spalluto ◽  
Karl-Norbet Klotz ◽  
Magdalena Bacilieri ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Activity Profile ◽  
Receptor Antagonists ◽  
Complete Structure ◽  
Structure Activity

scholarly journals Adenosine Receptors as Targets for Therapeutic Intervention

2014 ◽  
Vol 11 (1) ◽  
pp. 96-101 ◽  
Author(s):  
B Suvarna
Keyword(s):  
Medical Journal ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Receptor Subtypes ◽  
Therapeutic Application ◽  
Chemistry Research ◽  
Wide Range ◽  
The World ◽  
Selective Agonists ◽  
Receptor Modulators

Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide range of conditions, including cerebral and cardiac ischaemic diseases, sleep disorders, immune and inflammatory disorders and cancer. After more than three decades of medicinal chemistry research, a considerable number of selective agonists and antagonists of adenosine receptors have been discovered, and some have been clinically evaluated, although none has yet received regulatory approval. However, recent advances in the understanding of the roles of the various adenosine receptor subtypes, and in the development of selective and potent ligands, as discussed in this review, have brought the goal of therapeutic application of adenosine receptor modulators considerably closer. DOI: http://dx.doi.org/10.3126/kumj.v11i1.11054 Kathmandu University Medical Journal Vol.11(1) 2013: 96-101

Receptors subtypes involved in adenosine-mediated modulation of norepinephrine release from cardiac nerve terminals

2004 ◽  
Vol 82 (11) ◽  
pp. 1026-1031 ◽  
Author(s):  
Mojca Lorbar ◽  
Eugene S Chung ◽  
Arash Nabi ◽  
Katarina Skalova ◽  
Richard A Fenton ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Stellate Ganglion ◽  
Receptor Subtypes ◽  
Nerve Terminals ◽  
Norepinephrine Release ◽  
Receptor Antagonists ◽  
Cardiac Nerve ◽  
Mediated Effects ◽  
Discernible Effect ◽  
Rat Hearts

The objective of this study was to determine which adenosine receptor subtypes were involved in the modulation of norepinephrine release from cardiac nerve terminals. In addition, the persistence of adenosine-mediated effects was evaluated. Rat hearts attached to the stellate ganglion were isolated and perfused. The ganglion was electrically stimulated twice (S1 and S2), allowing 10 min between the stimulations. To determine adenosine receptor subtypes, selective and nonselective adenosine agonists and antagonists were infused following S1 and until the end of S2. To evaluate the persistence of adenosine-mediated effect on norepinephrine release, the stellate ganglion was stimulated a third (S3) and fourth (S4) time. Coronary effluents were collected to determine norepinephrine content. Adenosine and a selective A1 receptor agonist, CCPA, inhibited norepinephrine release by 49% and 54%, respectively. This effect was reversed by simultaneous infusion of nonspecific (8-SPT) and specific (DPCPX) A1 receptor antagonists. Selective A2A (CGS 21680) and A3 (AB-MECA) receptor agonists had no discernible effect on norepinephrine release. Similarly, adenosine A2A receptor antagonists CSC and DMPX did not alter the dose-response relation between norepinephrine release and adenosine. Finally, the inhibitory effects of adenosine on norepinephrine release did not persist 10 min subsequent to the removal of adenosine. Adenosine inhibited norepinephrine release primarily via the adenosine A1 receptor. This effect of adenosine was of short duration. Adenosine A2A and A3 receptors were either absent or functionally insignificant in the regulation of norepinephrine release in the rat heart.Key words: adenosine, norepinephrine, receptor, rat, neurotransmitters.

scholarly journals Structure–Activity Relationships and Molecular Modeling of 1,2,4-Triazoles as Adenosine Receptor Antagonists

2012 ◽  
Vol 3 (9) ◽  
pp. 715-720 ◽  
Author(s):  
Jens Carlsson ◽  
Dilip K. Tosh ◽  
Khai Phan ◽  
Zhan-Guo Gao ◽  
Kenneth A. Jacobson
Keyword(s):  
Molecular Modeling ◽  
Adenosine Receptor ◽  
Receptor Antagonists ◽  
Structure Activity Relationships ◽  
Structure Activity

Discovery and development of macrolides as anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Rongli Liu ◽  
Yani Hou ◽  
Yijun Gu
Keyword(s):  
Anticancer Agents ◽  
Rational Design ◽  
Chemotherapeutic Agents ◽  
Lifestyle Changes ◽  
Therapeutic Interventions ◽  
The Past ◽  
Development Of Resistance ◽  
Structure Activity ◽  
Activity Structure ◽  
Life Threatening

: Cancer is a life-threatening destructive disease. In the past several decades, the incidence of cancer has been dramatically increased mostly due to lifestyle changes. Chemotherapy plays an important role in the treatment of cancer, but the development of resistance against chemotherapeutic agents, the side effects, and non-specific toxicity threatens the efficiency of anticancer agents. Accordingly, it is necessary to develop novel anticancer drugs. Beyond the classical antibacterial activity, macrolides also demonstrated potential effects against both drug-sensitive and drug-resistant cancers through modulating diverse targets and signaling pathways, so rational design of macrolides may generate valuable therapeutic interventions for the treatment of cancers. The purpose of the present review article is to outline the current developments in macrolides with an emphasis on anticancer activity, structure-activity relationships, and mechanisms of action to lay the path for the development of novel macrolide anticancer candidates.

Synthesis and Structure−Activity Relationships of a New Set of 2-Arylpyrazolo[3,4-c]quinoline Derivatives as Adenosine Receptor Antagonists

2000 ◽  
Vol 43 (16) ◽  
pp. 3118-3124 ◽  
Author(s):  
Vittoria Colotta ◽  
Daniela Catarzi ◽  
Flavia Varano ◽  
Lucia Cecchi ◽  
Guido Filacchioni ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Quinoline Derivatives ◽  
Receptor Antagonists ◽  
Structure Activity Relationships ◽  
Structure Activity
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