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In this work, we synthesized substances and evaluated the potential leishmanicidal activity. Thirty-four (34) compounds from different chemical classes were selected for a simple synthesis in overall good yields, eight of which are not described in the literature. From the 34 compounds evaluated for preliminary leishmanicidal activity, three can be considered as prototypes for the development of leishmanicidal agents. Computational chemistry calculations, including comparative modeling of the enzyme arginase from Leishmania amazonensis and a molecular docking simulation of the synthesized molecules into the active site of the model were carried out. Key words: Leishmaniasis, arginase, molecular docking, thiourea, bisguanidine, amidine, biological evaluation, comparative modeling

The compounds, N-{2-[(5-amino-1,3,4-thiadiazol-2-yl)difluoromethyl]-4-chlorophenyl}acetamide (1: X = Cl) and N-{2([(5-amino-1,3,4-thiadiazol-2-yl)difluoromethyl]-4-bromo-phenyl}acetamide (1: X = Br), are isostructural. The molecules are near ‘‘V’’ shaped with the angles between the two aromatic planes ca. 84° in each case. The various intermolecular interactions, namely N–H···O, N–H···N, N–H···F, and C–H···N hydrogen bonds and C–H···π, C–Cl···π and C–O···π interactions, generate 3-D arrays. Compound (1: X = Cl) crystallizes in the monoclinic space group P21/c with a = 16.9032(7) A, 10.2193(4) A, c = 7.5227(4) A, β = 100.179(3)° and Z = 4. Compound (1: X = Br) crystallizes in the monoclinic space group P21/c with a = 17.2119(4) A, 10.2167(2) A, c = 7.5677(2) A, β = 100.326(2)° and Z = 4. Generation of 3-D arrays via N–H···O, N–H···N, N–H···F, and C–H···N hydrogen bonds and C–H···π, C–Cl···π and C–O···π intermolecular interactions.

This work describes the synthesis of new 3-trifluoromethylindoles. Different isatins were trifluoromethylated using (trifluoromethyl) trimethylsilane (Me3SiCF3) as a nucleophilic agent giving new 3-hydroxy-3-(trifluoromethyl)indolin-2-one. Different “one-step” procedures to transform the latter compounds into the reduced indoles were attempted, but failed. For the synthesis of the new trifluoromethylindoles the corresponding 2-oxo-3-(trifluoromethyl)indoles were reduced using borane/THF complex to furnish 3-(trifluoromethyl)indolin-3-ol that additionally were dehydrated using thionyl chloride in pyridine to give excellent yields of the desired products.

This paper describes the versatility of N-Acyl-3,3-difluoro-2-oxoindoles, obtained from the the reaction of N-acylisatins with (diethylamino)sulphur trifluoride (DAST) which, on opening of the heterocyclic ring by reactions with nucleophiles, lead to the formation of a variety of products: reaction with water yields 2-(2-amidoacyl)-2,2-difluoroacetic acids, with alcohols yields alkyl 2-(2-amidoacyl)-2,2-difluoroacetates, with amines and glycine yields 2-(2-amidoacyl)-2,2-difluoroacetamides and with thiosemicarbazides yields difluorothiosemicarbazide derivatives. The latter undergo acid-catalysed cyclizations to yield N-(2-((5-aminoaryl-1,3,4-thiadiazol-2-yl)difluoromethyl)-4-(R)-phenyl)acetamide. The X-ray structure of N-(2-((5-amino-1,3,4-thiadiazol-2-yl)difluoromethyl)-4-methylphenyl)acetamide has been determined.

Several compounds of great pharmacological interest contain the triazole and imidazole rings. In order to find new drugs with antileishmanial activity we have synthesized and evaluated new imidazole and triazole compounds carrying either the carbaldehyde or the difluoromethylene functionalities against promastigote forms of Leishmania amazonensis. Among the compounds tested difluoromethylene azoles 4b and 8f have inhibited the parasite growth significantly. Our results show that the introduction of the difluoromethylene moieties has turned the inactive carbaldehydes into active antileishmanial compounds.

The trifluoromethyl group (CF3) is present in commercially available drugs of various therapeutic classes owing to its ability to modify and frequently improve their biological activities. Efavirenz is a trifluoromethylated inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) that shows good results in anti-HIV chemotherapy. With the objective of developing efficient non-nucleoside compounds, we have designed and synthesized some new 3-hydroxy-2-oxo-3-trifluoromethylindole as potential RT inhibitors. We used different substituted isatins as starting materials. The final products contain the group CF3, present in Efavirenz, and a pharmacophoric group, oxoindole. We have used molecular docking with HIV-1 RT as a tool to design putative non-nucleoside reverse transcriptase inhibitors (NNRTIs). Based on the calculation results obtained, a series of new 3-hydroxy-2-oxo-3-trifluoromethylindoles were synthesized as a novel class of potential RT inhibitors. The results showed that these compounds are capable of important interactions with the NNRT binding site, which encouraged us to submit them for biological assay. All compounds studied are significantly active in the RNA-dependent DNA-polymerase (RDDP) assay, and were not toxic toward the Vero cell line. Hence, the designed molecules represent good starting structures for further modification and structure–activity relationship (SAR) studies.

In the title compound, C8H8N4O3S·H2O, strong hydrogen bonding results in the formation of a number of chains and dimers, which combine to give a three-dimensional hydrogen-bonded framework.

A method for protecting the 8,9-double bond of (+)-limonene ( 1 ) is described. The key step is the 1,3-dipolar-cycloaddition of benzylazide to 1 , which affords N-benzyl-N-[9-(1-p-menthenylidene)]-amine ( 2 ) and N-benzyl-N-[8,9-(1-p-menthenylidene)]-amine ( 3 ).

A twisted conformation is found in the title compound, C8H9ClN2, with the ethanimidamide residue being twisted substantially to the benzene ring [dihedral angle = 66.54 (14)°]. The conformation about the C=N double bond [1.299 (3) Å] is Z. A two-dimensional array with a zigzag topology is formed in the crystal structure via N—H...N and N—H...Cl hydrogen-bonding interactions.

Two independent but virtually identical molecules comprise the asymmetric unit of the title compound, C16H14ClN3. The molecules have a slightly curved shape owing to puckering in the six-membered C4N2 ring; the respective dihedral angles formed between the benzene rings are 12.64 (7) and 11.72 (7)°. In the crystal, layers sustained by a combination of N—H...N hydrogen bonding as well as C—H...N and C—H...π contacts are formed; these stack along [011] and are connected by further C—H...π contacts.

The reaction of dry tetramethylammonium fluoride (TMAF) with 1-methyl-2,4,5-tribromoimidazole in different polar aprotic solvents was investigated. Products of reductive debromination were obtained rather than fluorine substitution, indicating that TMAF is strongly basic in such conditions. A reaction carried out in d6-DMSO showed that the solvent is the proton source. Dimethylformamide was less effective that DMSO, N,N-dimethylacetamide or N-methylpirrolidone as a proton donor and we were able to effect significant fluorination in this solvent.

The title molecule, also called 4-chloro-N,N-bis(trifluoromethanesulfonyl)aniline, C8H4ClF6NO4S2, has non-crystallographic twofold symmetry with the pseudo-axis aligned along the Cl—C...C—N backbone of the molecule: the SO2CF3 residues lie to either side of the benzene ring. In the crystal, the presence of C—H...O contacts lead to the formation of a sequence of 12-membered {...HC2NSO}2 synthons within a supramolecular chain aligned along [101].

This article presents the direct oxidation of limonene-oxide 1 with KIO4 in water, which is the best way to obtain the keto-aldehyde 3, an important intermediate in natural product synthesis. The cyclization of keto-aldehyde 3 with acidic Al2O3 proceeds chemoselectively to give ketone 4. These two reactions together increase the overall yield of ketone 4 to about 70% compared to 8% previously reported in the literature¹. Neste artigo apresentamos a oxidação direta do epóxi-limoneno 1 com KIO4 em água como uma melhor alternativa para se obter o ceto-aldeído 3, um importante intermediário na síntese de produtos naturais. O ceto-aldeído 3 é ciclizado com Al2O3-ácido de forma quimosseletiva produzindo, preferencialmente, a cetona 4. Estas duas reações elevam o rendimento total da síntese da cetona 4 para 70% em comparação com 8% pelo método citado na literatura¹.