Differences in the Structure and Antimicrobial Activity of Hydrazones Derived from Methyl 4-Phenylpicolinimidate.

Four novel methyl 4-phenylpicolinoimidate derivatives of hydrazone have been synthesized and evaluated for their antimicrobial activity, including tuberculostatic activity. The compounds obtained are condensates of hydrazonamide or hydrazide with 5-nitro-2-furaldehyde or 5-nitro-2-thiophenecarboxaldehyde. The antimicrobial activity of the tested compounds varied.

Relationship between the Crystal Structure and Tuberculostatic Activity of Some 2-Amidinothiosemicarbazone Derivatives of Pyridine.

Tuberculosis remains one of the most common diseases affecting developing countries due to difficult living conditions, the rapidly increasing resistance of strains and the small number of effective anti-tuberculosis drugs. This study concerns the relationship between molecular structure observed in a solid-state by X-ray diffraction and the N NMR of a group of pyridine derivatives, from which promising activity against was reported earlier. It was found that the compounds exist in two tautomeric forms: neutral and zwitterionic.

Synthesis, structure and biological activity of four new picolinohydrazonamide derivatives.

Four new picolinohydrazonamide derivatives, namely, 6-methyl-N'-(morpholine-4-carbonothioyl)picolinohydrazonamide, CHNOS, 6-chloro-N'-(morpholine-4-carbonothioyl)picolinohydrazonamide methanol monosolvate, CHClNOS·CHOH, 6-chloro-N'-(4-phenylpiperazine-1-carbonothioyl)picolinohydrazonamide, CHClNS, and 6-chloropicolinohydrazonamide, CHClN, have been synthesized and characterized by NMR spectroscopy and single-crystal low-temperature X-ray diffraction. In addition, their antibacterial and anti-yeast activities have been determined. The first three compounds adopt the zwitterionic form in the crystal structure regardless of the presence or absence of solvent molecules in the structure.

The structures of benzimidazole derivatives and their potential as tuberculostatics.

Tuberculosis still remains a very important problem, especially its multidrug resistant varieties (MDR-TB). Among the potential tuberculostatics, there are two benzimidazole derivatives, namely 5,6-dimethyl-2-phenylethylbenzo[d]imidazole (1) and (E)-5,6-dimethyl-2-styryl-1H-benzo[d]imidazole (2) which showed significant tuberculostatic activities, better than those of Pyrazinamide and Isoniazyd. Also, the cytotoxicity of 1 appeared promising.

Planarity of benzoylthiocarbazate tuberculostatics. IV. Polymorphs of N'-(1,3-dithiolan-2-ylidene)-4-nitrobenzohydrazide.

The search for new tuberculostatics is important considering the occurrence of drug-resistant strains of Mycobacterium tuberculosis. Three polymorphs of N'-(1,3-dithiolan-2-ylidene)-4-nitrobenzohydrazide (a potentially tuberculostatic agent), CHNOS, denoted (I1), (I2) and (I3), and the monohydrate of this compound, CHNOS·HO, (I4), have been characterized by single-crystal X-ray diffraction. The conformations of the molecules in all these structures are very similar.

Synthesis and biological activity of cyclolinopeptide A analogues modified with γ-bis(homo-phenylalanine).

Cyclolinopeptide A (CLA), an immunosuppressive nonapeptide derived from linen seeds, was modified with S or R-γ-bis(homo-phenylalanine) in positions 3 or 4, or both 3 and 4. These modifications changed the flexibility of new analogues and distribution of intramolecular hydrogen bonds. Analogues 11 c(Pro-Pro-Phe-S-γ-hhPhe-Leu-Ile-Ile-Leu-Val), 13 c(Pro-Pro-S-γ-hhPhe-R-γ-hhPhe-Leu-Ile-Ile-Leu-Val) and 15 c(Pro-Pro-R-γ-hhPhe-Phe-Leu-Ile-Ile-Leu-Val) existed as a mixture of stable cis/trans isomers of Pro-Pro peptide bond.

Planarity of benzoylthiocarbazate tuberculostatics. III. Diesters of 3-(2-hydroxybenzoyl)dithiocarbazic acid.

Searches for new tuberculostatic agents are important considering the occurrence of drug-resistant strains of Mycobacterium tuberculosis. The structures of three new potentially tuberculostatic compounds, namely isopropyl methyl (2-hydroxybenzoyl)carbonohydrazonodithioate, CHNOS, (Z)-benzyl methyl (2-hydroxybenzoyl)carbonohydrazonodithioate, CHNOS, and dibenzyl (2-hydroxybenzoyl)carbonohydrazonodithioate propan-2-ol monosolvate, CHNOS·CHO, were determined by X-ray diffraction. The mutual orientation of the three main fragments of the compounds, namely an aromatic ring, a dithioester group and a hydrazide group, can influence the biological activity of the compounds.

Planarity of benzoyldithiocarbazate tuberculostatics. II. Diesters of benzoyldithiocarbazic acid.

The emergence of drug-resistant strains of Mycobacterium tuberculosis has intensified efforts to identify new lead tuberculostatics. Our earlier studies concluded that the planarity of a molecule correlates well with its tuberculostatic activity. According to our hypothesis, only derivatives whose molecules are capable of adopting a planar conformation may show tuberculostatic activity.

Crystal structure of (3R)-3-benzyl-4-[(tert-but-oxy-carbon-yl)amino]-butanoic acid.

The characteristic feature of the title mol-ecule, C16H23NO4, is the syn configuration of the partially double amide C-N bond [C-N-C-O torsion angle = -14.8 (2)°]. The crystal packing is determined by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds, which link the mol-ecules into a double-chain structure extending along [010].

Planarity of benzoylhydrazine-dithiocarbazoate tuberculostatics. I. N'-Methyl-substituted 3,4-dichlorobenzoyl monoesters.

Methyl 2-(3,4-dichlorobenzoyl)-1-methylhydrazinecarbodithioate, C(10)H(10)Cl(2)N(2)OS(2), (F1), butyl 2-(3,4-dichlorobenzoyl)-1-methylhydrazinecarbodithioate, C(13)H(16)Cl(2)N(2)OS(2), (F2), and 3,4-dichloro-N-(2-sulfanylidene-1,3-thiazinan-3-yl)benzamide, C(11)H(10)Cl(2)N(2)OS(2), (F3), were studied by X-ray diffraction to test our hypothesis that planarity of aryloylhydrazinedithiocarbazic acid esters is a prerequisite for tuberculostatic activity. All compounds examined in this study are inactive and nonplanar due to twists along two specific bonds in the central frame of the molecules. The significant twist at the N-N bond, with an C-N-N-C(S) torsion angle of about 85°, results from repulsion caused by a methyl substituent at the N' atom of the hydrazide group.

Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity. IV. Diesters of benzoylcarbonohydrazonodithioic acid.

Dimethyl (3,4-dichlorobenzoyl)carbonohydrazonodithioate, C(10)H(10)Cl(2)N(2)OS(2), (D1), dibenzyl (3,4-dichlorobenzoyl)carbonohydrazonodithioate, C(22)H(18)Cl(2)N(2)OS(2), (D2), dimethyl (3,4-dichlorobenzoyl)-1-methylcarbonohydrazonodithioate, C(11)H(12)Cl(2)N(2)OS(2), (D3), 3,4-dichloro-N'-(1,3-dithiolan-2-ylidene)-N-methylbenzohydrazide, C(11)H(10)Cl(2)N(2)OS(2), (D4), were synthesized as potential tuberculostatics. Compound (D1) (with two molecules in the asymmetric unit) was the only one showing tuberculostatic activity of the same range as the common drugs isoniazid and pyrazinamide. The molecular structures of the studied compounds depend on the substitution at the N atom adjacent to the carbonyl group.

Synthesis, characterization, and tuberculostatic activity of novel 2-(4-nitrobenzoyl)hydrazinecarbodithioic acid derivatives.

Abstract: A series of novel -esters of 2-(4-nitrobenzoyl)hydrazinecarbodithioic acid and ,-diesters of (4-nitrobenzoyl)carbonohydrazonodithioic acid were synthesized by reaction of 4-nitrobenzohydrazide and -methyl-4-nitrobenzohydrazide with carbon disulfide and alkyl halides in the presence of triethylamine. Novel 5-(4-nitrophenyl)-1,3,4-oxadiazoles were also obtained. The structures were confirmed by IR, NMR, and mass spectroscopy, and by elemental analysis.

Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity. III. Mono- and diesters of 3-(pyrazin-2-ylcarbonyl)dithiocarbazic acid.

Methyl 2-(pyrazin-2-ylcarbonyl)hydrazinecarbodithioate, C(7)H(8)N(4)OS(2), (E1), N'-[bis(methylsulfanyl)methylidene]pyrazine-2-carbohydrazide, C(8)H(10)N(4)OS(2), (F1), N'-[bis(methylsulfanyl)methylidene]-6-methoxypyrazine-2-carbohydrazide, C(9)H(12)N(4)O(2)S(2), (F2), and methyl 1-methyl-2-(pyrazin-2-ylcarbonyl)hydrazinecarbodithioate, C(8)H(10)N(4)OS(2), (G1), can be considered as derivatives of classical (thio)amide-type tuberculostatics, and all are moderately active against Mycobacterium tuberculosis. This study was undertaken in a search for relationships between activity and specific intramolecular interactions, especially conjugations and hydrogen-bond contacts, and the molecular structures were compared with respective amine analogues, also active against the pathogen. Despite the differences between the amine and carbonyl groups with opposite functions in the hydrogen bond, the two types of structure show a surprisingly similar planar geometry, mostly due to the conjugations aided by the bifurcated intramolecular hydrogen-bond contact between the N-H group of the central hydrazide group as donor and a pyrazine N atom and an S atom of the dithio function as acceptors.

Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity. II. Crystal structures of 3-[amino(pyrazin-2-yl)methylidene]-2-methylcarbazic acid esters.

Four compounds showing moderate antituberculostatic activity have been studied to test the hypothesis that the planarity of the 2-[amino(pyrazin-2-yl)methylidene]dithiocarbazate fragment is crucial for activity. N'-Anilinopyrazine-2-carboximidamide, C(11)H(11)N(5), D1, and diethyl 2,2'-[({[amino(pyrazin-2-yl)methylidene]hydrazinylidene}methylidene)bis(sulfanediyl)]diacetate, C(14)H(19)N(5)O(4)S(2), B1, maintain planarity due to conjugation and attractive intramolecular hydrogen-bond contacts, while methyl 3-[amino(pyrazin-2-yl)methylidene]-2-methyldithiocarbazate, C(8)H(11)N(5)S(2), C1, and benzyl 3-[amino(pyrazin-2-yl)methylidene]-2-methyldithiocarbazate, C(14)H(15)N(5)S(2), C2, are not planar, due to methylation at one of the N atoms of the central N-N bond. The resulting twists of the two molecular halves (parts) of C1 and C2 are indicated by torsion angles of 116.

Synthesis, structure, and tuberculostatic activity of dimethyl benzoylcarbonohydrazonodithioates.

Abstract: New dimethyl benzoylcarbonohydrazonodithioates were obtained by CS addition to arylcarboxylic acid hydrazides and methylation of the formed adduct. The new derivatives were tested for their activity against . Some compounds exhibited high activity toward sensitive and resistant strains.

N-triazinylammonium tetrafluoroborates. A new generation of efficient coupling reagents useful for peptide synthesis.

A new generation of triazine-based coupling reagents (TBCRs), designed according to the concept of "superactive esters", was obtained by treatment of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) chloride with lithium or silver tetrafluoroborate. The structure of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate was confirmed by X-ray diffraction. Activation of carboxylic acids by using this reagent proceeds via triazine "superactive ester".

Synthesis, structure and pharmacology of acyl-2,6-xylidines.

L-2-perhydroheterocyclicalkyl acids were condensed with 2,6-xylidine. 8 new optically active acyl-2,6-xylidines were obtained. Absolute configuration of acyl-2,6-xylidines were selected for pharmacological examinations.

Synthesis, structure, and antibacterial activity of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid and 4-oxo-1, 4-dihydrocinnoline-3-carboxylic acid derivatives as isosteric analogues of quinolones.

Chemical modification of cinnoxacin was studied with the aim of improving its antibacterial activity and spectrum. A series of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid derivatives was synthesized and their in vitro antibacterial activity was evaluated. These derivatives were designed as isosteric analogues of fluoroquinolones and are characterized by the presence of an imine group instead of an oxo group at the 4-position and a nitrogen atom in position 2.