Azole antifungals agents

The Corey-Chaykovsky reaction incited some applications in medicinal chemistry. During the synthesis of analogs of fluconazole, an azole antifungal agent, treatment of 49 with 1 led to the corresponding epoxide, which was subsequently... 

This is not discussed in detail since mechanisms of resistance have been carefully reviewed (Ghannoum and Rice 1999). It was pointed out that resistance has not been associated with modification of the structure. For the 1,2,4-triazoles that have been widely used, their effect is due to inhibition of the synthesis of ergosterol that is the dominant component of fungal cell membranes. Resistance is generally associated with modification of the target enzymes, for example, the epoxidation of squalene (Terbinafine) or 14a-demethylase (Fluconazole). Resistance of Candida albicans to the azole antifungal agent fluconazole demonstrated, however, the simultaneous occurrence of several types of mechanism for resistance (Perea et al. 2001) ... 

Perea S, JL Lopez-Ribot, WR Kirkpatrick, RK McAtee, RA Santillan, M Martinez, D Calabrese, D Sanglard, TP Patterson (2001) Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antibicrob Agents Chemother 45 2676-2684. 

Systemic adverse effects associated with vaginal azoles are less frequent than with oral products. Local discomfort such as burning may occur with the first application. Fifteen percent of patients experience gastrointestinal side effects with orally administered antifungal agents.13 Oral ketoconazole is associated with hepatic toxicity at a rate of 1 in 15,000.14... 

Raab [123] presented a discussion on the topical clinical pharmacology of miconazole and two other azole antifungal agents. 

Posaconazole, launched last year in the UK, is the newest member of the azole class of antifungal agents to reach the market. It is indicated for the treatment and prophylaxis of a range of invasive fungal infections, including aspergillosis,... 

Drugs that may interact with halopehdol include anticholinergic agents, azole antifungal agents, carbamazepine, lithium, rifamycins, and fluoxetine. 

Drugs that may be affected by proton pump inhibitors include azole antifungal agents (eg, itraconazole, ketoconazole), benzodiazepines, cilostazol, clarithromycin, digoxin, phenytoin, salicylates, sulfonylureas, and warfarin. Drugs that may affect proton pump inhibitors include sucralfate and clarithromycin. 

Hypersensitivity to fluconazole or to any excipients in the product. There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungal agents use with caution in patients with hypersensitivity to other azoles. P.986... 

Drugs that may interact with rifabutin include the following Anticoagulants, azole antifungal agents, benzodiazepines, beta blockers, buspirone, corticosteroids, cyclosporine, delavirdine, doxycycline, hydantoins, indinavir, rifamycins, losartan, macrolide antibiotics, methadone, morphine, nelfinavir, quinine, quinidine, theophylline, aminophylline, tricyclic antidepressants, and zolpidem. 

Talele, T. T. and Kulkami, V. M. (1999) Three-dimensional quantitative structure-activity relationship (QSAR) and receptor mapping of cytochrome P-450(14 alpha DM) inhibiting azole antifungal agents.. /. Chem. Inf. Comput. Sci. 39, 204-210. 

The metabolism of ciclosporin is inhibited by diltiazem, verapamil, azole antifungal agents, erythromycin and clarithromycin with resultant potential for renal, hepatic and CNS toxicity. These interactions have been investigated as a cost saving device in organ transplant recipients, with the aim of using a lower dose of ciclosporin to achieve immunosuppression. 

Therapy of fungal arthritis consists of amphotericin B in combination with surgical debridement. Azole antifungal agents including itraconazole, fluconazole, voriconazole, and posaconazole, are promising in the therapy of fungal arthritis. 

Inhibitors of the CYP3A4 isoenzyme could increase systemic dofetilide exposure. Inhibitors of this isoenzyme (e.g., macrolide antibiotics, azole antifungal agents, protease inhibitors, serotonin reuptake inhibitors, amiodarone, cannabinoids, diltiazem, grapefruit juice, nefazadone, norfloxacin, quinine, and zafirlukast) should be cautiously coadministered with TIKOSYN, because they can potentially increase dofetilide levels... 

Cyclosporin is metabolised by the hepatic cytochrome P-450 enzyme system, and enzyme induction by phenobarbital, phenytoin, carbamazepine, or rifampicin will drastically increase the clearance of cyclosporin. Concurrent administration of these drugs has caused rejection of transplanted organs. Conversely, the use of enzyme inhibitors, such as erythromycin or the azole antifungal agents, e.g. ketoconazole, will increase the blood concentrations of cyclosporin leading to an increased risk of toxic side effects. 

Sheehan D3, Hitchcock CA, Sibley CM Current and emerging azole antifungal agents. Clin Microbiol Rev 1999 12 40. [PMID 9880474]... 

Oral Antifungal Agents ORAL AZOLE DERIVATIVES... 

Ketoconazole, 1% shampoo, apply every 3-4 days Nizoral A-D Synthetic azole antifungal agent with activity versus Pityrosporum ovale, a fungus that may cause seborrhea and dandruff. Massage over entire scalp for 3 minutes. Rinse thoroughly and repeat application. 

The key step in the synthesis of novel azole antifungal agents has been performed by asymmetric dihydroxylation117 using a modified AD-mix118-120 (equation 20). The reaction occurs in excellent yields at room temperature in t-BuOH- water as solvent. 

Azole derivatives currently available for oral treatment of systemic mycosis include fluconazole (Diflucan), itraconazole (Sporonax), and ketoconazole (Nizoral). As discussed in Chapter 48 Antifungal Agents, imidazole derivatives act by affecting the permeability of the cell membrane of... 

Use of Excluded Volume Features in the Rationalization of the Activity Data of Azole Antifungal Agents... 

S., Artico, M., Costi, R., Di Santo, R., Ragno, R. Molecular modeling of azole antifungal agents active against Candida albicans. 1. A comparative molecular field analysis study. J. Med. Chem. 1996, 39, 1227-1235. 

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