Editing Imidazole (section)

===Pharmaceutical derivatives===
Imidazole substituents are found in many pharmaceuticals such as anticancer drug [[mercaptopurine]]. The imidazole group is present in many [[fungicide]]s and [[Antifungal medication|antifungal]], [[antiprotozoal]], and [[antihypertensive]] medications. Imidazole is part of the [[theophylline]] molecule, found in tea leaves and coffee beans, that stimulates the [[central nervous system]].

A number of substituted imidazoles, including [[clotrimazole]], are selective inhibitors of [[nitric oxide synthase]].<ref>{{cite journal|last1=Castaño|first1=T.|last2=Encinas|first2=A.|last3=Pérez|first3=C.|last4=Castro|first4=A.|last5=Campillo|first5=N. E.|last6=Gil|first6=C.|date=2008|title=Design, synthesis, and evaluation of potential inhibitors of nitric oxide synthase|journal=Bioorg. Med. Chem.|volume=16|issue=11|pages=6193–6206|pmid=18477512|doi=10.1016/j.bmc.2008.04.036|url=https://digital.csic.es/bitstream/10261/87090/1/accesoRestringido.pdf|type=Submitted manuscript|hdl=10261/87090|access-date=2018-07-24|archive-date=2023-03-06|archive-url=https://web.archive.org/web/20230306094210/https://digital.csic.es/bitstream/10261/87090/1/accesoRestringido.pdf|url-status=live}}</ref><ref>{{cite journal|last1=Bogle|first1=R. G.|last2=Whitley|first2=G. S.|last3=Soo|first3=S. C.|last4=Johnstone|first4=A. P.|last5=Vallance|first5=P.|date=1994|title=Effect of anti-fungal imidazoles on mRNA levels and enzyme activity of inducible nitric oxide synthase|journal=Br. J. Pharmacol.|volume=111|issue=4 |pages=1257–1261|pmc=1910171|pmid=7518297|doi=10.1111/j.1476-5381.1994.tb14881.x}}</ref> Other biological activities of the imidazole [[pharmacophore]] relate to the downregulation of intracellular [[calcium|Ca<sup>2+</sup>]] and [[potassium|K<sup>+</sup>]] fluxes, and interference with translation initiation.<ref>{{cite journal|last1=Khalid|first1=M. H.|last2=Tokunaga|first2=Y.|last3=Caputy|first3=A. J.|last4=Walters|first4=E.|date=2005|title=Inhibition of tumor growth and prolonged survival of rats with intracranial gliomas following administration of clotrimazole|journal=J. Neurosurg.|volume=103|issue=1 |pages=79–86|pmid=16121977|doi=10.3171/jns.2005.103.1.0079}}</ref>

The substituted imidazole derivatives are valuable in treatment of many systemic [[fungal]] [[infections]].<ref>{{cite book |title= Comprehensive Pharmacy Review |author= Leon Shargel |year= 2007 |edition= 6th |pages= 930|publisher= Lippincott Williams & Wilkins | isbn=9780781765619}}</ref> Imidazoles belong to the class of [[Antifungal medication#Imidazole.2C triazole.2C and thiazole antifungals|azole antifungals]], which includes [[ketoconazole]], [[miconazole]], and [[clotrimazole]].

For comparison, another group of azoles is the triazoles, which includes [[fluconazole]], [[itraconazole]], and [[voriconazole]]. The difference between the imidazoles and the triazoles involves the mechanism of inhibition of the [[Cytochrome P450|cytochrome P450 enzyme]]. The N3 of the imidazole compound binds to the heme iron atom of ferric cytochrome P450, whereas the N4 of the triazoles bind to the heme group. The triazoles have been shown to have a higher specificity for the cytochrome P450 than imidazoles, thereby making them more potent than the imidazoles.<ref>{{cite book |title= Veterinary Pharmacology and Therapeutics |edition= 9th |pages= 1019–1020 |last1= Davis |first1= Jennifer L. |last2= Papich |first2= Mark G. |last3= Heit |first3= Mark C. |year= 2009 |chapter= Chapter 39: Antifungal and Antiviral Drugs |editor1-last= Riviere |editor1-first= Jim E. |editor2-last= Papich |editor2-first= Mark G. |chapter-url= https://books.google.com/books?id=ievLulSqwBAC |publisher= Wiley-Blackwell |isbn= 978-0-8138-2061-3 }}</ref>

Some imidazole derivatives show effects on insects, for example [[sulconazole nitrate]] exhibits a strong anti-feeding effect on the [[keratin]]-digesting Australian carpet beetle larvae ''[[Anthrenocerus australis]]'', as does [[econazole nitrate]] with the common clothes moth ''[[Tineola bisselliella]]''.<ref>{{cite journal|last1=Sunderland|first1=M. R.|last2=Cruickshank|first2=R. H.|last3=Leighs|first3=S. J.|date=2014|title=The efficacy of antifungal azole and antiprotozoal compounds in protection of wool from keratin-digesting insect larvae|journal=Textile Res. J.|volume=84|issue=9|pages=924–931|doi=10.1177/0040517513515312|s2cid=135799368}}</ref>