Amino Acid Derivatives,Part 4: Synthesis and Anti‐HIV Activity of New Naphthalene Derivatives

A new series of 2‐(naphthalen‐2‐yloxy)‐N‐[(aryl‐5‐thioxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐3‐yl)methyl] acetamides 5a–f was synthesized from naphthalene‐derived glycine derivative 2 via the hydrazinoacetamide analogs 4a–f . Alternatively, treatment of 4a with H₂SO₄ afforded 2‐(naphthalen‐2‐yloxy)‐N‐((5‐(phenylamino)‐1,3,4‐thiadiazol‐2‐yl)methyl) acetamide 6a . Alkylation or sulphonylation of 5a afforded the S‐alkylated derivatives 7 and 8 , respectively. Interestingly, treatment of 3 with methoxide ion gave the triazine derivative 9 . The synthesized compounds have been screened for their inhibitory activity against HIV‐1 and HIV‐2 in MT‐4 cells. However, 7 was found to be the potent inhibitor in vitro for the replication of HIV‐1 (EC₅₀ = 0.20 μg/mL), suggesting a new lead in the development of an antiviral agent.     

New pyrazole derivative 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole: synthesis and assessment of some biological activities

The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti‐inflammatory effects, this study sought to evaluate the analgesic, anti‐inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole. During the acetic acid‐induced abdominal writhing test, treatments with 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole reduced abdominal writhing, while during the formalin test, 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole also reduced carrageenan‐induced paw edema and cell migration during the carrageenan‐induced pleurisy test. As demonstrated by the model of the isolated organ, 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole exhibits a vasorelaxant effect attenuated by Nω‐nitro‐l ‐arginine methyl ester, 1H‐[1,2,4]oxadiazolo[4,3‐alpha]quinoxalin‐1‐one, tetraethylammonium or glibenclamide. 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole also blocked CaCl₂‐induced contraction in a dose‐dependent manner. Suggesting a safe toxicity profile, 5‐[1‐(4‐fluorophenyl)‐1H‐pyrazol‐4‐yl]‐2H‐tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K⁺ channels observed in the vasorelaxant effect.     

Synthesis of Novel 2,5‐Disubstituted 1,3,4‐Thiadiazoles for Their Potential Anticonvulsant Activity: Pharmacophoric Model Studies

A series of novel N¹‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N⁴‐(4‐substituted benzaldehyde)‐semicarbazone 1 – 12 , N¹‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N⁴‐[1‐(4‐substituted phenyl)ethanone]‐semicarbazone 13 ‐ 16 , and N¹‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N⁴‐[1‐(4‐substituted phenyl) (phenyl) methanone]‐semicarbazone 17 – 20 were synthesized for their anticonvulsant activity. The chemical structures of the compounds were proved by elemental and spectral (IR, ¹H‐NMR, ¹³C‐NMR, and MS) analysis. The anticonvulsant potential of the compounds was investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. Compound 19 was found to possess significant anticonvulsant activity in both the models employed for anticonvulsant evaluation. Compounds 8 , 13 , 15 , and 16 also demonstrated a marked anticonvulsant property. The results of the present study validated that the pharmacophore model with four binding sites is essential for anticonvulsant activity. The efforts were also made to establish structure‐activity relationships among the synthesized compounds.     

Design,Synthesis, Biological Evaluation,and Docking Study of Acetylcholinesterase Inhibitors: New Acridone‐1,2,4‐oxadiazole‐1,2,3‐triazole Hybrids

In this study, novel acridone‐1,2,4‐oxadiazole‐1,2,3‐triazole hybrids were designed, synthesized, and evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity. Among various synthesized compounds, 10‐((1‐((3‐(4‐methoxyphenyl)‐1,2,4‐oxadiazol‐5‐yl)methyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)acridin‐9(10H)‐one 10b showed the most potent anti‐acetylcholinesterase activity (IC₅₀ = 11.55 μm ) being as potent as rivastigmine. Also docking outcomes were in good agreement with in vitro results confirming the dual binding inhibitory activity of compound 10b .     

Synthesis and in‐vitro Cytotoxicity of Poly‐functionalized 4‐(2‐Arylthiazol‐4‐yl)‐4H‐chromenes

A new series of 4‐aryl‐4H‐chromenes bearing a 2‐arylthiazol‐4‐yl moiety at the 4‐position were prepared as potential cytotoxic agents. The in‐vitro cytotoxic activity of the synthesized 4‐aryl‐4H‐chromenes was investigated in comparison with etoposide, a well‐known anticancer drug, using MTT colorimetric assay. Among them, the 2‐(2‐chlorophenyl)thiazol‐4‐yl analog 4b showed the most potent activity against nasopharyngeal epidermoid carcinoma KB, medulloblastoma DAOY, and astrocytoma 1321N1, and compound 4d bearing a 2‐(4‐chlorophenyl)thiazol‐4‐yl moiety at the 4‐position of the chromene ring exhibited the best inhibitory activity against breast cancer cells MCF‐7, lung cancer cells A549, and colon adenocarcinoma cells SW480 with IC₅₀ values less than 5 μM. The ability of compound 4b to induce apoptosis was confirmed in a nuclear morphological assay by DAPI staining in the KB and MCF‐7 cells.     

Novel 3,6‐Disubstituted 7H‐1,2,4‐Triazolo[3,4‐b][1,3,4]thiadiazines: Synthesis,Characterization, and Evaluation of Analgesic / Anti‐inflammatory,Antioxidant Activities

In this study, the synthesis of a new series of 3,6‐disubstituted‐7H‐1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazine 1a – 4c compounds derived from 4‐amino‐3‐substituted‐1,2,4‐triazole‐5‐thiones 1 – 4 is described. All of the synthesized compounds were screened for their possible analgesic / anti‐inflammatory, antioxidant activities and gastric toxicity. The compound 2c was found to have both significant analgesic and consistent anti‐inflammatory activity without inducing any gastric lesions along with minimal lipid peroxidation. A deep insight into the structures of the active compounds revealed that the compounds carrying an electron withdrawing group (a chloride or fluoride) on the phenyl ring at 6‐position of the condensed heterocyclic derivatives exhibited noticeable higher activity.     

Synthesis,Hypoglycaemic, Hypolipidemic and PPARγ Agonist Activities of 5‐(2‐Alkyl/aryl‐6‐Arylimidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene‐1,3‐Thiazolidinediones

A novel series of 5‐(2‐alkyl/aryl‐6‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene‐1,3‐thiazolidinediones were synthesized as possible PPARγ agonists. The structures of these target molecules were established by spectral and analytical data. All the newly synthesized compounds were screened for their in vivo hypoglycaemic and hypolipidemic activity in male Wistar rats. Further, compounds with good activity were screened for PPARγ agonist activity. Among the screened compounds, 5‐{[2‐Cyclohexyl‐6‐(4‐methoxyphenyl)imidazo[2,1‐b] [1,3,4]thiadiazol‐5‐yl]methylene}‐1,3‐thiazolidine‐2,4‐dione (3i) exhibits promising hypoglycaemic and hypolipidemic activity via potential PPARγ agonist activity.     

5-Nitroimidazole-based 1,3,4-thiadiazoles: heterocyclic analogs of metronidazole as anti-Helicobacter pylori agents

A series of 5‐nitroimidazole‐based 1,3,4‐thiadiazoles were prepared and tested for antibacterial activity against Helicobacter pylori. The anti‐H. pylori activity of target compounds along with the commercially available antimicrobial metronidazole was evaluated by comparing the inhibition‐zone diameters determined by the paper disc diffusion bioassay. From our bioassay results against 20 clinical isolates it is evident that piperazinyl, 4‐methylpiperazinyl, 3‐methylpiperazinyl, and 3,5‐dimethylpiperazinyl analogs ( 6a , 6b , 6e , and 6f , respectively) and pyrrolidine derivative 7 had strong activity at 0.5 µg/disc (average of inhibition zone >20 mm) while metronidazole had no activity at this dose. Compound 6f containing the 3,5‐dimethylpiperazinyl moiety at the 2‐position of the 5‐(1‐methyl‐5‐nitro‐1H‐imidazol‐2‐yl)‐1,3,4‐thiadiazole skeleton was the most potent compound tested at low concentrations.     

Discovery of Novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole Derivatives as Potential Anti‐Inflammatory Agents

A novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative 5 with good anti‐inflammatory activity was identified from our in‐house library. Based on hit compound 5 , two series of 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative 6a – g and 7a – h were designed and synthesized as novel anti‐inflammatory agents. Most of synthesized compounds exhibited good inhibitory activity on NO and TNF‐α production in LPS‐stimulated RAW 264.7 macrophages, in which the compound 6e showed most potent inhibitory activity on NO (IC₅₀ = 0.86 μm ) and TNF‐α (IC₅₀ = 1.87 μm ) production. Further evaluation revealed that compound 6e displayed more potent in vivo anti‐inflammatory activity than ibuprofen did on xylene‐induced ear oedema in mice. Additionally, Western blot analysis revealed that compound 6e could restore phosphorylation level of IκBα and protein expression of p65 NF‐κB in LPS‐stimulated RAW 264.7 macrophages.     

Synthesis of Novel Substituted Thiourea and Benzimidazole Derivatives Containing a Pyrazolone Ring as Anti‐Inflammatory Agents

Two series of new 1‐(alkyl/aryl)‐3‐{2‐[(5‐oxo‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)amino]phenyl}thioureas 2a – h and 5‐[2‐(substituted amino)‐1H‐benzimidazol‐1‐yl]‐4H‐pyrazol‐3‐ols 3a – i were designed and synthesized as anti‐inflammatory agents. The cyclooxygenase inhibitory activity of the newly synthesized compounds was investigated. All the compounds showed non‐selective inhibition of COX‐1 and COX‐2 enzymes which was consistent with their docking results. Compounds 2c , 2f , 2g , 3b , and 3g that showed the highest COX‐2 inhibitory activity were selected for further in vivo testing as anti‐inflammatory agents using diclofenac as a reference drug. Two of the test compounds ( 2c and 3b ) showed potent anti‐inflammatory activity comparable to that of diclofenac with lower ulcerogenic effect relative to indomethacin. SAR study of the two series as cyclooxygenase inhibitors and anti‐inflammatory agents was also provided.     

Facile Synthesis and In‐Vitro Antitumor Activity of Some Pyrazolo[3,4‐b]pyridines and Pyrazolo[1,5‐a]pyrimidines Linked to a Thiazolo[3,2‐a]benzimidazole Moiety

The key precursor E‐3‐(N,N‐dimethylamino)‐1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)prop‐2‐en‐1‐one 4 was synthesized in good yield using Gold's reagent. The reaction of enaminone 4 with 5‐amino‐3‐aryl‐1‐phenylpyrazoles 5a , b in refluxing acetic acid in the presence of sulphuric acid, yielded pyrazolo[3,4‐b]pyridines 7a , b . Similarly, pyrazolo[1,5‐a]pyrimidines 10a , b and 14a – f were prepared by reaction of enaminone 4 with 5‐amino‐1H‐pyrazoles 8a , b and 12a – f , respectively. The structure of pyrazolo[1,5‐a]pyrimidine 10b was determined by X‐ray diffraction. The synthesized compounds were tested for their in‐vitro antitumor activity against the colon cancer cell line CaCo‐2; their cytotoxicity against the normal fibroblast cell line BHK was explored as well. Some of the tested compounds exhibited cell growth inhibitory activity. The significant antitumor activity of compound 14f against the CaCo‐2 cell line (IC₅₀ = 0.5 μg/mL) was coupled with a lower toxicity against BHK (IC₅₀ = 2.3 μg/mL).     

Unusual base‐catalyzed exchange in the synthesis of deuterated PF‐2413873a

The preparation of deuterated PF‐2413873 (4‐[3‐cyclopropyl‐1‐(methanesulfonylmethyl)‐5‐methyl‐1H‐pyrazol‐4‐yl]oxy‐2,6‐dimethylbenzonitrile, 1) is described for use as a bioanalytical standard in clinical trials. Two strategies were investigated. The sulfone‐containing substituent was labelled by base‐catalyzed exchange, but unacceptable deuterium loss was noted under assay conditions. Alternatively, labelling 4‐cyano‐3,5‐dimethylphenol was achieved by heating with deuterium oxide over platinum oxide. After building up the pyrazole ring we discovered that, during the subsequent alkylation to attach the methylthiomethyl group, the base, potassium t‐butoxide, caused unwanted scrambling of deuteriums on the aromatic portion and the methylthiomethyl group. Thus, it was necessary to remove all base‐labile hydrogens to prevent their exchange. This was accomplished by alkylating the pyrazole with per‐deuterated chloromethyl methylsulfide, oxidation to the sulfone, and selective removal of its deuteriums by treatment with sodium hydroxide. The unusual sensitivity and selectivity of these base‐promoted exchange reactions are discussed. Thus, 4‐[3‐cyclopropyl‐1‐(methanesulfonylmethyl)‐5‐methyl‐1H‐pyrazol‐4‐yl]oxy‐[²H₆]2,6‐dimethyl‐[3,5‐²H]benzonitrile (17) was obtained, labelled with eight deuterium atoms and an acceptable D₀/D₈ ratio. Copyright © 2009 John Wiley & Sons, Ltd.     

2‐Aryl‐3‐(1H‐Azol‐1‐yl)‐1H‐Indole Derivatives: A New Class of Antimycobacterial Compounds – Conventional Heating in Comparison with MW‐Assisted Synthesis

2‐Aryl‐3‐(1H‐imidazol‐1‐yl and 1H‐1,2,4‐triazol‐1‐yl)‐1H‐indole derivatives were synthesized and tested for their in‐vitro antifungal and antimycobacterial activities. These indole derivatives were devoid of antifungal activity against the tested strains of Candida spp. Yet, they exhibited an interesting antitubercular activity against Mycobacterium tuberculosis reference strain H₃₇Rv.     

Synthesis and Anticonvulsant Properties of New N‐Mannich Bases Derived from 3,3‐Diphenyl‐ and 3‐Ethyl‐3‐methyl‐pyrrolidine‐2,5‐diones. Part III

Twenty‐four new N‐[(4‐phenylpiperazin‐1‐yl)‐methyl] derivatives of 3,3‐diphenyl‐ ( 7 – 18 ) and 3‐ethyl‐3‐methyl‐pyrrolidine‐2,5‐dione ( 19 – 30 ) were synthesized and evaluated for their anticonvulsant activity in the maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The acute neurological toxicity was determined using the rotorod screen. Eleven compounds were active and revealed protection only in electrically induced seizures (MES). In the whole series the most effective compound was N‐[{4‐(3‐trifluoromethylphenyl)‐piperazin‐1‐yl}‐methyl]‐3,3‐diphenyl‐pyrrolidine‐2,5‐dione ( 14 ) with an ED₅₀ value of 30.3 mg/kg (p.o. rats) in the MES test. To explain the possible mechanism of action, for chosen active derivatives 7 , 8 , 9 , 11 , 14 , 23 , and 26 , their influence on Na_V1.2 sodium channel currents was evaluated in vitro. The crystallographic structures for several molecules ( 8 , 10 , and 11 ) were solved.     

Synthesis and Pharmacological Evaluation of Some Novel Thebaine Derivatives: N‐(Tetrazol‐1H‐5‐yl)‐6,14‐endoethenotetrahydrothebaine Incorporating the 1,3,4‐Oxadiazole or the 1,3,4‐Thiadiazole Moiety

In this study, we synthesized some novel N‐(tetrazol‐1H‐5‐yl)‐6,14‐endoethenotetrahydrothebaine 7α‐substituted 1,3,4‐oxadiazole and 1,3,4‐thiadiazole derivatives as potential analgesic agents. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C NMR, 2D NMR, and high‐resolution mass spectral data. The analgesic activity was evaluated by a rat‐hot plate test model and a rat tail‐flick model. Compound 12 showed analgesic activity higher than that of morphine. In addition to a histopathological and biochemical evaluation, the LD₅₀ dose for the most active compound 12 was determined.     

Synthesis and structure–activity relationships of pyrazolo‐[3,4‐b]pyridine derivatives as adenosine 5'‐monophosphate‐activated protein kinase activators

A series of pyrazolo[3,4‐b]pyridine derivatives were designed, synthesized, and evaluated for their activation activity toward adenosine 5'‐monophosphate‐activated protein kinase (AMPK). According to the enzyme activity, the pyrazole N?H exposure and para substitution on the diphenyl group were proved to be essential for the activation potency. Compound 17f showed equal activation compared with A‐769662. In the molecular modeling study, compound 17f exhibited important hydrogen bond interaction with Lys29, Asp88, and Arg83. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays on the NRK‐49F cell line showed that potent enzyme activators could effectively inhibit cell proliferation, especially for 17f (EC₅₀ [AMPKα1γ1β1] = 0.42 μM, efficacy = 79%; IC₅₀ [NRK‐49F cell line] = 0.78 μM). These results might provide new insights to explore novel AMPK activators.     

Syntheses and radiofluorination of two derivatives of 5‐cyano‐indole as selective ligands for the dopamine subtype‐4 receptor

Two fluoroethoxy substituted derivatives, namely 2‐[4‐(2‐(2‐fluoroethoxy)phenyl)‐piperazin‐1‐ylmethyl]indole‐5‐carbonitrile ( 5a ) and 2‐[4‐(4‐(2‐fluoroethoxy)‐phenyl)piperazin‐1‐ylmethyl]indole‐5‐carbonitrile ( 5b ) were synthesized as analogs of the selective D₄ receptor ligand 2‐[4‐(4‐fluorophenyl)piperazin‐1‐ylmethyl]indole‐5‐carbonitrile (FAUC 316). In vitro characterization using CHO‐cells expressing different dopamine receptor subtypes gave K_i values of 2.1 ( 5a ) and 9.9 nM ( 5b ) for the dopamine D₄ subtype and displayed a 420‐fold D₄‐selectivity over D₂ receptors for 5b . The para‐fluoroethoxy substituted candidate 5b revealed substantially reduced α₁ and serotoninergic binding affinities in comparison to the ortho‐fluoroethoxy substituted compound. In order to provide potential positron emission tomography (PET) imaging probes for the dopamine D₄ receptor, ¹⁸F‐labelling conditions using [¹⁸F]fluoroethyl tosylate were optimized and led to radiochemical yields of 81 ± 5% ( [¹⁸F]5a ) and 47 ± 4% ( [¹⁸F]5b ) (n = 3, decay‐corrected and referred to labelling agent), respectively. Thus, ¹⁸F‐fluoroethylation favourably at the para position of the phenylpiperazine moiety of the 5‐cyano‐indole framework proved to be tolerated by D₄ receptors and could also be applied to alternative scaffolds in order to develop D₄ radioligand candidates for PET with improved D₄ receptor affinity and selectivity. Copyright © 2005 John Wiley & Sons, Ltd.     

1‐[(2,3‐Dihydro‐1‐benzofuran‐2‐yl) methyl]piperazines as novel anti‐inflammatory compounds: Synthesis and evaluation on H3R/H4R

The histamine receptors (HRs) are members of G‐protein‐coupled receptor superfamily and traditional targets of huge therapeutic interests. Recently, H₃R and H₄R have been explored as targets for drug discovery, including in the search for dual‐acting H₃R/H₄R ligands. The H₄R, the most recent histamine receptor, is a promising target for novel anti‐inflammatory agents in several conditions such as asthma and other chronic inflammatory diseases. Due to similarity with previously reported ligands of HRs, a set of 1‐[(2,3‐dihydro‐1‐benzofuran‐2‐yl)methyl]piperazines were synthesized and evaluated in competitive binding assays as H₃R/H₄R ligands herein. The results showed the compounds presented affinity (K_i) for H₃R/H₄R in micromolar range, and they are more selective to H₃R. All the compounds showed no important cytotoxicity to mammalian cells. The phenyl‐substituted compound LINS01005 has shown the higher affinity of the set for H₄R, but no considerable selectivity toward this receptor over H₃R. LINS01005 showed interesting anti‐inflammatory activity in murine asthma model, reducing the eosinophil counts in bronchoalveolar lavage fluid, as well as the COX‐2 expression. The presented compounds are valuable prototypes for further improvements to achieve better anti‐inflammatory agents.     

Synthesis of New 2,3‐Dihydroquinazolin‐4(1H)‐one Derivatives for Analgesic and Anti‐inflammatory Evaluation

Starting from isatoic anhydrides, several new 2,3‐dihydroquinazolin‐4(1H)‐one derivatives bearing chalcone or pyrazole or thiazole moieties at the third position were synthesized. The analgesic and anti‐inflammatory activities for most compounds were studied at a dose level of 50 mg/kg via the acetic‐acid‐induced writhing‐response method and carrageenan‐induced edema method, respectively. The study showed that the chalcones bearing a 4‐chlorophenyl group 4c or 4‐nitrophenyl group 4b were the most active ones as analgesics. Both chalcone 4c and N‐phenyl pyrazole bearing 4‐methoxy phenyl group 5b showed a higher anti‐inflammatory activity than celecoxib but still lower than that of diclofenac sodium. Moreover, the chalcone 4c has nearly the same ulcerogenic index as the selective cyclooxygenase‐2 inhibitor celecoxib.     

A Novel Antifungal Agent with Broad Spectrum: 1‐(4‐Biphenylyl)‐3‐(1H‐imidazol‐1‐yl)‐1‐propanone

A series of (1‐substituted aryl)‐3‐(1H‐imidazol‐1‐yl)‐1‐propanones was synthesized through the N‐alkylation of imidazole with 3‐dimethylamino‐1‐(substituted aryl)‐1‐propanone hydrochlorides (ketonic Mannich bases). A second series of N¹‐substituted imidazoles was obtained by the reduction of the carbonyl function of the imidazole–ketones in the previous series by means of NaBH₄. All of the compounds were evaluated for antifungal activity against 16 strains of Candida, and 3‐(1H‐imidazol‐1‐yl)‐1‐(4‐biphenylyl)‐1‐propanone emerged as a broad‐spectrum antifungal agent. Several 3‐(1H‐imidazol‐1‐yl)‐1‐(2′‐(substituted benzyl)oxyphenyl)‐1‐propanones were also active towards Candida kefyr.