Bioisosteres in drug discovery: focus on tetrazole

• Published in: Future medicinal chemistry 2020-01, Vol.12 (2), p.91-93
• Main Authors: Zou, Yulin, Liu, Li, Liu, Junxiong, Liu, Guocheng
• Format: Article
• Language: English
• Subjects: Acids; Alzheimer's disease; Angiotensin; Angiotensin II; Angiotensin-converting enzyme inhibitors; antibacterial; Antibiotics; anticancer; antifungal; Antifungal agents; antihypertensive; Antimalarial agents; Antiviral agents; Bacterial infections; Bioavailability; Blood flow; Blood pressure; Blood vessels; Cancer; Candidiasis; Carboxylic acids; Cardiovascular disease; Clinical medicine; Congestive heart failure; Cough; Cytochrome; Drug resistance; Fungal infections; Gram-positive bacteria; Heart failure; Hypertension; Kidneys; Meningitis; Mortality; Multidrug resistance; Neurodegenerative diseases; Pathogens; Patients; Peptidyl-dipeptidase A; Pharmaceutical sciences; Staphylococcus infections; tetrazole; Tropical diseases
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2019-0288

Some prodrug approaches to tetrazole drugs have been implemented to improve oral bioavailability and replacement of carboxylic acid by tetrazole has the potential to increase the lipophilicity and bioavailability and reduce the side effects of drugs (3). [...]tetrazole has the capacity to exert various noncovalent interactions with biological targets and its derivatives possess diverse pharmacological properties, such as anti-Alzheimer’s disease (4), antiangiogenic (5), antibacterial (6), anticancer (7), antifungal (8), antimalarial (9), antitubercular (10) and antiviral (11) activities. Oteseconazole, a potential best-in-class treatment option for patients suffering from recurrent vulvovaginal candidiasis, is the first US FDA approved drug for the treatment of this common disease. Besides which, oteseconazole has strong potential in the fight against other fungal infections, including azole-resistant fungal infections (15). Losartan, as the first angiotensin-II receptor antagonist, can keep blood vessels from narrowing, which lowers blood pressure and improves blood flow. [...]it could also be used in the management of hypertension and heart failure, particularly in patients who develop cough with angiotensin-converting enzyme inhibitors. Some of them not only exhibited great activity against drug-sensitive organisms, but also demonstrated potential in vitro and in vivo activity against drug-resistant, including multidrug-resistant and extensively drug-resistant pathogens. [...]several of them have already been used in clinical practice, such as tomelukast (LY171883), a leukotriene antagonist, and they also showed potential activity against Alzheimer’s disease (18).