Application of the Pentafluorosulfanyl Group as a Bioisosteric Replacement

Candidiasis, caused by yeasts of the genus Candida, is the second cause of superficial and mucosal infections and the fourth cause of bloodstream infections. Although some antifungal drugs to treat candidiasis are available, resistant strains to current therapies are emerging. Therefore, the search for new candicidal compounds is certainly a priority. In this regard, a series of indazole and pyrazole derivatives were designed in this work, employing bioisosteric replacement, homologation, and molecular simplification as new anticandidal agents. Compounds were synthesized and evaluated against C. albicans, C. glabrata, and C. tropicalis strains. The series of 3-phenyl-1H-indazole moiety (10a–i) demonstrated to have the best broad anticandidal activity. Particularly, compound 10g, with N,N-diethylcarboxamide substituent, was the most active against C. albicans and both miconazole susceptible and resistant C. glabrata species. Therefore, the 3-phenyl-1H-indazole scaffold represents an opportunity for the development of new anticandidal agents with a new chemotype.

Download Full-text

Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate

ACS Medicinal Chemistry Letters ◽

10.1021/acsmedchemlett.1c00140 ◽

2021 ◽

Author(s):

Olga Bobiļeva ◽

Raitis Bobrovs ◽

Iveta Kaņepe ◽

Liene Patetko ◽

Gints Kalniņš ◽

...

Keyword(s):

Bioisosteric Replacement

Download Full-text

The Trifluoromethyl Group as a Bioisosteric Replacement of the Aliphatic Nitro Group in CB1 Receptor Positive Allosteric Modulators

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.9b00252 ◽

2019 ◽

Vol 62 (10) ◽

pp. 5049-5062 ◽

Cited By ~ 13

Author(s):

Chih-Chung Tseng ◽

Gemma Baillie ◽

Giulia Donvito ◽

Mohammed A. Mustafa ◽

Sophie E. Juola ◽

...

Keyword(s):

Nitro Group ◽

Cb1 Receptor ◽

Allosteric Modulators ◽

Trifluoromethyl Group ◽

Bioisosteric Replacement ◽

Positive Allosteric Modulators

Download Full-text

Separation of Quercetin’s Biological Activity from Its Oxidative Property through Bioisosteric Replacement of the Catecholic Hydroxyl Groups with Fluorine Atoms

Journal of Agricultural and Food Chemistry ◽

10.1021/jf3018645 ◽

2012 ◽

Vol 60 (26) ◽

pp. 6499-6506 ◽

Cited By ~ 5

Author(s):

Suh Young Cho ◽

Mi Kyoung Kim ◽

Hyejung Mok ◽

Hyunah Choo ◽

Youhoon Chong

Keyword(s):

Biological Activity ◽

Hydroxyl Groups ◽

Bioisosteric Replacement ◽

Oxidative Property

Download Full-text

Bioisosteric replacement of central 1,2,4-oxadiazole ring of high affinity CB2 ligands by regioisomeric 1,3,4-oxadiazole ring

MedChemComm ◽

10.1039/c7md00296c ◽

2017 ◽

Vol 8 (8) ◽

pp. 1697-1705 ◽

Cited By ~ 2

Author(s):

Dominik Heimann ◽

Corinna Lueg ◽

Henk de Vries ◽

Bastian Frehland ◽

Dirk Schepmann ◽

...

Keyword(s):

High Affinity ◽

Bioisosteric Replacement ◽

Pharmacokinetic Properties

Three pairs of regioisomeric 1,2,4- and 1,3,4-oxadiazoles were synthesized as selective CB2 ligands. Although the 1,3,4-oxadiazoles should have better physicochemical and pharmacokinetic properties, their CB2 affinity was reduced.

Download Full-text