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The saturated vapor pressure of the antifungal drug griseofulvin depending on temperature was measured by the transpiration method. The standard molar enthalpy of sublimation of the studied compound calculated from these data is (141.8 ± 1.2) kJ mol−1. Using thermogravimetric techniques, the vaporization enthalpy of drug was determined and the enthalpy of sublimation at reference temperature was calculated. It is shown that the values of this thermodynamic function derived by both these methods are equal within the experimental uncertainty. The space clusterization approach was applied for the estimation of thermodynamic sublimation functions of griseofulvin and structurally related compounds. In addition, the fusion temperature, enthalpy of fusion and heat capacity of the drug were measured by DSC. [ABSTRACT FROM AUTHOR]

Cocrystal formation of 4-aminobenzoic acid (PABA) has been screened with a variety of pyrimidine, pyridine and benzamide derivatives to understand how hydrogen bond donor/acceptor ratios and the position of a substituting group of the coformers affect cocrystallization. Four new cocrystals with 6-methyluracil (6-MeUr), barbituric acid (BarbAc), 2-hydroxybenzamide (2-OHBZA), 4-hydroxybenzamide (4-OHBZA) and one salt with emoxypine (EMX) have been successfully obtained from solvent evaporation experiments, and their crystal structures have been determined. Analysis of the hydrogen bonding motifs has shown that all the two-component crystals, except for the [PABA + 4-OHBZA] cocrystal, feature acid…amide or acid…pyridine heterosynthons between the components. The melting temperatures and crystal lattice energy values of the novel PABA multi-component crystals have been described. The temperature dependences of the 6-MeUr and EMX saturation vapour pressure have been studied, and the sublimation thermodynamic functions have been calculated. The thermodynamic functions of cocrystal formation based on PABA have been calculated and analyzed by the diagram method. [ABSTRACT FROM AUTHOR]

On the basis of the values contained in the literature published in 1900-2016, we have developed an experimental database including sublimation Gibbs energies, enthalpies, and melting temperatures of 1515 compounds. We have also suggested an algorithm of database fragmentation which includes groups/clusters with structurally similar compounds. For this aim we used Tanimoto similarity coefficients. Clusterization was carried out for each substance of the test set. All the points within a cluster were smoothed by a linear function in the coordinates of Gibbs energy vs melting temperature. Using the training and test sets, it has been shown that the algorithm suggested by us describes experimental data well (rms = 3.89 kJ·mol-1). We have developed quantitative structure-property relationship models based on HYBOT physicochemical descriptors and melting points in order to predict sublimation Gibbs energies and enthalpies of molecular crystals. The developed approach was applied to determine cocrystal formation thermodynamics. Twenty nine out of 30 seven cocrystals selected in the literature have been predicted correctly (78% of the correct matches). [ABSTRACT FROM AUTHOR]

The inert gas transpiration technique was used for measuring the vapor pressures of the following biologically active compounds: 4-aminobenzoic acid, nicotinic acid, 4-aminobenzamide, 4-pyridinecarboxamide, N-(2-chloro-3-pyridinyl)-benzenesulfonamide, 4-nitro- N-2-thiazolyl-benzenesulfonamide, and 4-amino- N-(5-methyl-3-isoxazolyl)-benzenesulfon-amide in the appropriate temperature ranges. Differential scanning calorimetric analysis was applied to obtain the temperature and molar enthalpy of melting of the compounds studied. Standard molar enthalpies, entropies, and Gibbs energies of sublimation were derived at T = 298.15 K from the temperature dependences of the vapor pressure of the compounds. The obtained results allowed the estimation of the relationship between the sublimation thermodynamic parameters and the thermophysical properties of the substances. Correlation equations were used for calculating the saturated vapor pressures on the basis of the melting temperatures, sublimation enthalpies, and physicochemical HYBOT descriptors. [ABSTRACT FROM AUTHOR]

The temperature dependencies of the saturated vapor pressure for antituberculous drug compounds: pyrazinecarboxamide and three isonicotinic acid hydrazides were obtained using the method of inert gas-carrier transfer. The standard sublimation molar enthalpies, entropies and Gibbs energies were derived at T = 298.15 K. The temperature and fusion molar enthalpy of the compounds were measured using the differential scanning calorimetry technique. The influence of the structure of the studied compounds on the crystal lattice energy and volatility was analyzed. It was estimated that the saturated vapor pressure of the studied substances decreases when the molecule polarizability and donor-acceptor ability increase. [ABSTRACT FROM AUTHOR]

Abstract: The thermodynamic aspects of sublimation processes of three sulfonamides with the general structures C6H5–SO2NH–C6H4–R (R=4-NO2) and 4-NH2–C6H4–SO2NH–C6H4–R (R=4-NO2; 4-CN) were studied by investigating the temperature dependence of vapor pressure using the transpiration method. These data together with those obtained earlier for C6H5–SO2NH–C6H4–R (R=4-Cl) and 4-NH2–C6H4–SO2NH–C6H4–R (R=4-Cl; 4-OMe; 4-C2H5) were analyzed and compared. A correlation was derived between sublimation Gibbs free energies and the sum of H-bond acceptor factors of the molecules. Solubility processes of the compounds in water, phosphate buffer with pH 7.4 and n-octanol (as phases modeling various drug delivery pathways) were investigated and corresponding thermodynamic functions were calculated as well. Thermodynamic characteristics of the sulfonamides solvation were evaluated. Also in this case a correlation between solubility/solvation Gibbs free energy values and the sum of H-bond acceptor factors was observed. For the sulfonamides with various substituents at para-position the processes of transfer from one solvent (water or buffer) to n-octanol were studied by a diagram method combined with analysis of enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is possible through the present approach, leads to the insight that the contribution of these terms is different for different molecules (entropy- or enthalpy-determined). Thus, in contrast to the interpretation of only the Gibbs free energy of transfer (extensively used for pharmaceuticals in the form of the partition coefficient, log P), the analysis of thermodynamic functions of the transfer process provides additional mechanistic information. This may be important for further evaluation of the physiological distribution of drug molecules and may provide a better understanding of biopharmaceutical properties of drugs. [Copyright &y& Elsevier]

Temperature dependency of saturated vapour pressure and thermochemical characteristics of fusion processes for 2-, 3- and 4-methoxybenzoic acids (anisic acids) were measured and thermodynamic functions of sublimation, fusion, and evaporation calculated. A new approach to split specific and nonspecific energetic terms in the crystal lattice was developed. For methoxybenzoic acid isomers as well as for a number of analogous molecules, a parameter describing molecular packing density by the ratio of free volume of the molecules in the crystal lattice and van der Waals molecular volume is defined. Its relationship to Gibbs energy of sublimation and to the respective melting points was analysed. Temperature dependencies of solubility in buffers with pH 2.0 and 7.4, n-octanol and n-hexane were measured. The thermodynamic functions of solubility, solvation and transfer processes were deduced. Concentration dependence of partition coefficients for the outlined isomers was measured. Specific and nonspecific solvation terms were distinguished using the transfer from the ‘inert’ n-hexane to the other solvents. Comparison analysis of specific and nonspecific interactions in the solid state and in solution was carried out. A diagram enabling analysis of the mechanism of the partitioning process was applied. It was found that position of substituents essentially affects the mechanism of partitioning in buffer pH 2.0, however, at pH 7.4, the mechanism is independent of the position of the substituent. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3883–3896, 2008 [ABSTRACT FROM AUTHOR]

Abstract: Temperature dependency of saturated vapour pressure for Fenbufen (FBF) was obtained. Heat capacities for Fenbufen, Diflunisal (DIF), and Flurbiprofen (FBP) were measured, and standard thermodynamic functions of sublimation were calculated (FBF: ; ; ; DIF: ; ; ; FBP: ; ; ). Thermochemical parameters of fusion process for FBF were obtained, and evaporation enthalpy was estimated from fusion and sublimation enthalpies. Temperature dependencies of the solubility in buffer solutions (pHs 2.0 and 7.4), n-Octanol, and n-Hexane were measured, and solution and solvation thermodynamic functions were calculated. The transfer thermodynamic functions from n-Hexane to solvents used (imitating specific “drug–solvent” interaction), and from buffer solutions to n-Octanol (imitating partitioning/distribution processes) were analyzed. Specific/non-specific “drug–solvent” interaction ratios in terms of solvation enthalpies were estimated. All studied solutions are characterized by prevalence of non-specific “drug–solvent” interactions. A difference exists between mechanisms of partitioning and distribution of studied drugs. [Copyright &y& Elsevier]

Abstract: Crystal structures of N-(2-chlorophenyl)-benzene-sulfonamide (I), N-(2,3-dichlorophenyl)-benzene-sulfonamide (II), N-(4-chlorophenyl)-benzene-sulfonamide (III) were solved by X-ray diffraction method. Temperature dependencies of saturated vapor pressure and thermodynamic functions of sublimation process were calculated (I: ; ; ; II: ; ; ; III: ; ; ). Thermochemical parameters of fusion process for the compounds were obtained. Enthalpies of evaporation were estimated from enthalpies of sublimation and fusion. Temperature dependencies of the solubility in water, n-octanol and n-hexane were measured. The thermodynamic functions of solubility and solvation processes were deduced. Specific and non-specific solvation terms were distinguished using the transfer from the “inert”n-hexane to the other solvents. The transfer processes of the molecules from water to n-octanol were analyzed and main driven forces were established. [Copyright &y& Elsevier]

Abstract: Saturated vapor pressures for a number of parabens (methyl- (MePB); ethyl- (EtPB), n-propyl- (PrPB) and n-butyl- (BuPB)) were obtained and from their respective temperature dependences the sublimation enthalpy, , and sublimation entropy, , as well as their respective relative fractions in the process calculated. The sublimation enthalpies are: (MePB)=98.8±0.8; (EtPB)=100.9±0.7; (PrPB)=123.7±0.6; (BuPB)=108.4±0.8kJmol-1. The obtained values are discussed with regard to X-ray data from the literature. Theoretical calculations of the respective crystal lattice energies were carried out and compared to the experimental data. The following parameters were analyzed: (a) energetic contribution of van der Waals forces and hydrogen bonding to the total packing energy of the crystals; (b) contributions of the different fragments of the paraben molecules to the packing energy; (c) influence of bias of the supposed C–H distances on the result of the calculation procedure. Enthalpies of evaporation were estimated from the measured enthalpies of sublimation and enthalpies of fusion, and compared with literature data. Moreover, the thermodynamic functions of solvation of the molecules in water and in a number of n-alcohols were evaluated. The thermodynamic terms (Gibbs energy, enthalpy and entropy) of the solvation process were split up in their respective specific and nonspecific fraction, and these values compared for all combinations of parabens and solvents. The influence of mutual saturation of the phases in the water–octanol system on the partitioning process of the molecules is also discussed. [Copyright &y& Elsevier]

A temperature dependence of saturated vapor pressure of isavuconazole (IVZ), an antimycotic drug, was found by using the method of inert gas-carrier transfer and the thermodynamic functions of sublimation were calculated at a temperature of 298.15 K. The value of the compound standard molar enthalpy of sublimation was found to be 138.1 ± 0.5 kJ·mol−1. The IVZ thermophysical properties—melting point and enthalpy—equaled 302.7 K and 29.9 kJ mol−1, respectively. The isothermal saturation method was used to determine the drug solubility in seven pharmaceutically relevant solvents within the temperature range from 293.15 to 313.15 K. The IVZ solubility in the studied solvents increased in the following order: buffer pH 7.4, buffer pH 2.0, buffer pH 1.2, hexane, 1-octanol, 1-propanol, ethanol. Depending on the solvent chemical nature, the compound solubility varied from 6.7 × 10−6 to 0.3 mol·L−1. The Hansen s approach was used for evaluating and analyzing the solubility data of drug. The results show that this model well-described intermolecular interactions in the solutions studied. It was established that in comparison with the van't Hoff model, the modified Apelblat one ensured the best correlation with the experimental solubility data of the studied drug. The activity coefficients at infinite dilution and dissolution excess thermodynamic functions of IVZ were calculated in each of the solvents. Temperature dependences of the compound partition coefficients were obtained in a binary 1-octanol/buffer pH 7.4 system and the transfer thermodynamic functions were calculated. The drug distribution from the aqueous solution to the organic medium was found to be spontaneous and entropy-driven. [ABSTRACT FROM AUTHOR]

Single crystal of furazolidone (FZL) has been successfully obtained, and its crystal structure has been determined. Common and distinctive features of furazolidone and nitrofurantoin (NFT) crystal packing have been discussed. Combined use of QTAIMC and Hirshfeld surface analysis allowed characterizing the non-covalent interactions in both crystals. Thermophysical characteristics and decomposition of NFT and FZL have been studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and mass-spectrometry. The saturated vapor pressures of the compounds have been measured using the transpiration method, and the standard thermodynamic functions of sublimation were calculated. It was revealed that the sublimation enthalpy and Gibbs energy of NFT are both higher than those for FZL, but a gain in the crystal lattice energy of NFT is leveled by an entropy increase. The solubility processes of the studied compounds in buffer solutions with pH 2.0, 7.4 and in 1-octanol was investigated at four temperatures from 298.15 to 313.15 K by the saturation shake-flask method. The thermodynamic functions of the dissolution and solvation processes of the studied compounds have been calculated based on the experimental data. Due to the fact that NFT is unstable in buffer solutions and undergoes a solution-mediated transformation from an anhydrate form to monohydrate in the solid state, the thermophysical characteristics and dissolution thermodynamics of the monohydrate were also investigated. It was demonstrated that a combination of experimental and theoretical methods allows performing an in-depth study of the relationships between the molecular and crystal structure and pharmaceutically relevant properties of nitrofuran antibiotics. [ABSTRACT FROM AUTHOR]

Highlights: [•] Thermodynamic characteristics of sublimation process were investigated for 2-, 3- and 4-acetamidobenzoic acids. [•] Thermophysic parameters of melting processes were determined and enthalpies of vaporization were calculated for the isomers. [•] Sublimation thermodynamic parameters were compared with crystal structures of the isomers. [Copyright &y& Elsevier]

Highlights • Vapor pressures of Clonixin were determined by transpiration method. • The solubility of drug in four solvents were measured at different temperatures. • The distribution coefficients of Clonixin in system 1-octanol/ buffer were obtained. • Thermodynamics parameters of solubility, solvation and transfer for Clonixin were calculated. Abstract The saturated vapor pressure of Clonixin has been measured by the transpiration method in the temperature range of 419.15–443.15 К, and the thermodynamic functions of sublimation have been calculated. It has been found that the energy of the compound crystal lattice is equal to 108.4 kJ·mol−1. The drug solubility in solvents imitating biological media of the body (buffer pH 2.0 and 7.4, 1-octanol, hexane) and the distribution coefficients in the systems 1-octanol/buffer (pH 2.0 and 7.4) have been determined by the shake-flask method in the temperature range of 293.15–313.15 К. The compound solubility values in these solvents lie within the interval from 1.78·10−4 to 8.01·10−2 mol/l. The coefficients of the drug distribution from buffer pH 2.0 in 1-octanol are one order of magnitude higher than from buffer pH 7.4. Based on the experimental data, the thermodynamic functions of the drug dissolution, transfer and solvation have been calculated in the chosen solvents. [ABSTRACT FROM AUTHOR]

The solubility of eight biologically active nonaromatic compounds with a common 3-thia-1-aza-bicyclo fragment in 1-octanol and hexane was determined in the temperature range of T = 293.15-315.15 K. The solubility of the substances in alcohol is approximately 2 orders of magnitude higher than in alkane and varies within 3.0 x 10-3 to 2.1 x 10-1 and 7.1 x 10-5 to 13.5 x 10-3 mol. fractions, respectively. In accordance with the structure of the substituent at the para position of the phenyl ring, the studied compounds are arranged in the following order of decreasing solubility in both solvents: methyl- > fluoro- > ethyl- > trifluoromethyl- > cyano- > acetyl-. The ideal solubility of the substances in 1-octanol, calculated from thermophysical parameters was found to correlate with the reported experimental data. The activity coefficients of the substances in saturated solutions of organic solvents are determined by the method of distribution between two liquid phases. The thermodynamic aspects of the relationship between the processes of dissolution, melting, sublimation, and solvation of the substances are discussed. [ABSTRACT FROM AUTHOR]

Novel experimental data for physicochemical properties of the bioactive compound N-(5-ethyl-1,3,4-thiadiazole-2-yl)-4-nitrobenzamide have been obtained. The saturated vapor pressure of the studied compound has been measured within the temperature range of 431.15–457.15 K by the inert gas transpiration method. The shake flask method has been used to determine the solubility in buffer pH 7.4, n-hexane, ethanol, 1-octanol and distribution coefficients in the 1-octanol/buffer system at different temperatures. The van't Hoff and modified Apelblat models have been used to correlate the experimental solubility. The thermodynamic functions of sublimation and transfer have been investigated and discussed. [ABSTRACT FROM AUTHOR]

Vapor pressure of thioacetazone (TAZ) has been determined in the temperature range of 404.15–429.15 K by the transpiration method. The obtained data were used to calculate the standard molar enthalpy of sublimation that was found to be 164.1 kJ/mol at T = 298.15 K. The drug solubility was measured at seven temperatures from 288.15 to 318.15 K in modeling solvents: octanol, hexane and aqueous buffers pH 2.0 and 7.4 by the saturation shake-flask method by using spectrophotometric analysis. It has been found that TAZ has poor solubility in hexane and buffer solutions and limited solubility in octanol. The experimental data were well correlated by van’t Hoff and modified Apelblat equations. A temperature dependence of TAZ partition coefficient in the octanol/buffer pH 7.4 system has been derived. The partition coefficient value in this system (logP = 1.82) refers to the optimal interval for oral absorption drugs. The thermodynamic parameters of sublimation, solubility, solvation and transfer have been determined based on experimental data. The dominant effect of enthalpy and entropy contributions to the Gibbs energy of the investigated processes has been revealed. [ABSTRACT FROM AUTHOR]

The transpiration method was used to measure the vapor pressures as a function of temperature of the following antimicrobial drugs: ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin. Based on these results standard molar enthalpies, entropies and Gibbs energies of sublimation at T = 298.15 K were calculated and a correlation between the crystal lattice energy and the saturation vapor pressure in a number of fluoroquinolones was found. The thermophysical characteristics of the compounds studied were determined by DSC. The influence of different structural fragments of molecules substituents and the effects of hydrogen bonds in crystal lattices on the sublimation enthalpy was discussed. [ABSTRACT FROM AUTHOR]

Cocrystal screening of 4-hydroxybenzamide with a number of salicylates (salicylic acid, SA; 4-aminosalicylic acid, PASA; acetylsalicylic acid, ASA; and salicylsalicylic acid, SSA) was conducted to confirm the formation of two cocrystals, [SA+4-OHBZA] (1:1) and [PASA+4-OHBZA] (1:1). Their structures were determined using single-crystal X-ray diffraction, and the hydrogen-bond network topology was studied. Thermodynamic characteristics of salicylic acid cocrystal sublimation were obtained experimentally. It was proved that PASA cocrystallization with 4-OHBZA makes the drug more stable and prevents the irreversible process of decarboxylation of PASA resulting in formation of toxic 3-aminophenol. The pattern of non-covalent interactions in the cocrystals is described quantitatively using solid-state density functional theory followed by Bader analysis of the periodic electron density. It has been found that the total energy of secondary interactions between synthon atoms and the side hydroxyl group of the acid molecule in [SA+4-OHBZA] (1:1) and [PASA+4-OHBZA] (1:1) cocrystals is comparable to the energy of the primary acid-amide heterosynthon. The theoretical value of the sublimation enthalpy of [SA+4-OHBZA], 231 kJ/mol, agrees fairly well with the experimental one, 272 kJ/mol. The dissolution experiments with [SA+4-OHBZA] have proved that the relatively large cocrystal stability in relation to the stability of its components has a negative effect on the dissolution rate and equilibrium solubility. The [PASA+4-OHBZA] (1:1) cocrystal showed an enhancement of apparent solubility compared to that of the corresponding pure active pharmaceutical ingredient, while their intrinsic dissolution rates are comparable. [ABSTRACT FROM AUTHOR]

A newcocrystal of 2-hydroxybenzamide (A) with 4-acetamidobenzoicacid (B) has been obtained by the DSC screening method. Thermophysicalanalysis of the aggregate [A:B] has been conducted and a fusion diagramhas been plotted. Cocrystal formation from melts was studied by usingthermomicroscopy. A cocrystal single-crystal was grown and its crystalstructure was determined. The pattern of noncovalent interactionshas been quantified using the solid-state DFT computations coupledwith the Bader analysis of the periodic electron density. The sublimationprocesses of A-B cocrystal have been studied and its thermodynamicfunctions have been calculated. The classical method of substancetransfer by inert gas-carrier was chosen to investigate sublimationprocesses experimentally. The lattice energy is found to be 143 ±4 kJ/mol. It is lower than the sum of the corresponding values ofthe cocrystal pure components. The theoretical value of the latticeenergy, 156 kJ/mol, is in reasonable agreement with the experimentalone. A ternary phase diagram of solubility (A-B–ethanol) hasbeen plotted and the areas with solutions for growing thermodynamicallystable cocrystals have been determined. [ABSTRACT FROM AUTHOR]

Highlights: [•] The vapor pressures of novel bicyclo-derivatives of amine were measured. [•] Thermodynamic functions of sublimation were calculated. [•] The influence of substituent structure and chemical nature on the vapor pressure was studied. [Copyright &y& Elsevier]

Highlights: [•] Temperature dependencies of saturated vapor pressure of new bicyclo-derivatives were obtained. [•] Thermodynamic functions of sublimation and solvation were calculated. [•] The correlations between thermodynamic functions and molecular descriptors are discussed. [ABSTRACT FROM AUTHOR]

Temperature dependences of saturated vapor pressure foreight new molecular crystals of spiro-derivatives of 1,3-thiazinehave been determined by transport method by means of an inert gascarrier. Thermodynamic functions of sublimation have been calculated.The processes of substances fusion have been examined by differentialscanning calorimetry. The effect of alkyl substituents structure andintroduction of halogen atoms on sublimation properties of spiro-compoundshas been assessed. The correlation between thermodynamic parametersof sublimation processes and thermo-physical properties of the substancesand molecular descriptors is established. [ABSTRACT FROM AUTHOR]

Abstract: The article deals with the study of two polymorphic modifications in the space groups P21/c (white form) and P21/n (yellow form) of the tolfenamic acid. It also describes how the white form vapor pressure temperature dependence was determined by using the transpiration method and how thermodynamic parameters of the sublimation process were calculated. We have estimated the difference between the crystal lattice energies of the two polymorphic forms by solution calorimetry and found that the crystal lattice energy of the yellow form is 6.7±1.2kJmol−1 higher than that of the white form, whereas Gibbs free energies of the forms obtained from the vapor pressure temperature dependence are practically the same. The modifications under consideration are monotropically related. From the practical point of view, the white form is more preferable due to its lower crystal lattice energy and better performing procedure. We have also studied the solubility, solvation and transfer processes of the tolfenamic acid white form in buffers (with various values of pH and ionic strengths), n-hexane and n-octanol. The thermodynamic parameters of the investigated processes have been discussed and compared with those determined for others fenamates. In the study we estimated specific and non-specific contributions of the solvation enthalpic term of the fenamate molecules with the solvents as well. The driving forces of the transfer processes from the buffers with pH 7.4 and different ionic strengths to n-octanol were analyzed. It was found that the relationship between the enthalpic and entropic terms depends essentially on the ionic strength. For the considered fenamates the transfer processes of the neutral molecules and the ionic forms are enthalpy-determined, whereas for the niflumic acid this process is entropy-determined. [Copyright &y& Elsevier]

• Solubility of fluconazole was measured in buffers (pH 1.2, 2.0, 7.4), hexane and 1-octanol. • The melting temperature and enthalpy of fluconazole were obtained. • The vapor pressure and sublimation thermodynamics were determined. The solubility of the antifungal drug fluconazole in buffer solutions of different acidity (pH 1.2, 2.0 and 7.4), 1-octanol and hexane in the temperature range (293.15–313.15) K is determined by the isothermal saturation method. The solubility of the compound in selected solvents increases as follows: hexane, buffer pH 7.4, buffer pH 2.0, 1- octanol, buffer pH 1.2, and does not exceed 0.2 mol·l−1. The temperature dependence of fluconazole saturated vapor pressure is obtained by the transpiration method. The sublimation enthalpy of the compound equals 131.4 ± 0.9 kJ·mol−1. Based on the HYBOT descriptors, it is shown that it is possible to estimate the sublimation enthalpy of compounds structurally similar to fluconazole. [ABSTRACT FROM AUTHOR]