Hit-to-Lead studies: The discovery of potent adamantane amide P2X7 receptor antagonists
A Hit-to-Lead programme was carried out resulting in the discovery of the potent P2X7 antagonists 16 and 31.
References (14)
- et al.
Prog. Med. Chem.
(2001) - et al.
J. Biol. Chem.
(1994) - et al.
Blood
(1998) Pharm. News
(1996)Physiol. Rev.
(2002)Drug Dev. Res.
(2001)- et al.
Handbook Exp. Pharmacol.
(2001)
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Synthetic molecules as P2X7 receptor antagonists: A medicinal chemistry update focusing the therapy of inflammatory diseases
2023, European Journal of PharmacologyDevelopment and clinical translation of P2X7 receptor antagonists: A potential therapeutic target in coronary artery disease?
2022, Pharmacology and TherapeuticsDesign and synthesis of adamantane-1-carbonyl thiourea derivatives as potent and selective inhibitors of h-P2X4 and h-P2X7 receptors: An Emerging therapeutic tool for treatment of inflammation and neurological disorders
2022, European Journal of Medicinal ChemistryCitation Excerpt :These include Suramin, Reactive Blue 2, PPADS and its derivatives [6]. It has been found that most of the known inhibitors for P2X receptor subtypes did not fulfill drug-ability criteria due to the large molecular weight (>700) and high lipophilicity (clogP>6) [7]. Selective antagonists of P2X receptors will find wide range of therapeutic applications for inflammation, pain, osteoporosis, neurodegenerative disorders, spinal cord injury, hypertension, and urinary incontinence.
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2019, Trends in ChemistryCitation Excerpt :Amantadine and memantine are extremely simple adamantane derivatives which were among the first pharmaceutical hits in the 1960s, and are used to ameliorate side-effects of Parkinson’s medication levodopa and symptoms of Alzheimer’s, respectively. Since AstraZeneca’s initial research into adamantyl-based compounds as P2X7 antagonists (1; Figure 3) for treatment of chronic inflammatory disease [49], academic research groups have shown the use of trifluoroadamantanes (SMW139) [50], cubanes (2; Figure 3), carboranes (3; Figure 3) [48,49], and bisnoradamantane [51] to antagonize the same receptor [52,53]. In addition to its polycyclic nature, cubane has the added property of being an isostere of benzene [54].