Acetic Acid Hydrazide Research Articles

2-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)- and 2-(2,2-dioxo-1,4-dihydro-2H-2lambda6-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamides as potent and selective peptide deformylase inhibitors.

Potent, selective, and structurally new inhibitors of the Fe(II) enzyme Escherichia coli peptide deformylase (PDF) were obtained by rational optimization of the weakly binding screening hit (5-chloro-2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid hydrazide (1). Three-dimensional structural information, gathered from Ni-PDF complexed with 1, suggested the preparation of two series of related hydroxamic acid analogues, 2-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-N-hydroxy-acetamides (A) and 2-(2,2-dioxo-1,4-dihydro-2H-2lambda(6)-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamides (B), among which potent PDF inhibitors (37, 42, and 48) were identified. Moreover, two selected compounds, one from each series, 36 and 41, showed good selectivity for PDF over several endoproteases including matrix metalloproteases. However, these compounds showed only weak antibacterial activity.

Regioselective role of the hydrazide moiety in the formation of complex pyrrole–pyrazole systems

The treatment of alkyl 2-chloroacetoacetate with ethyl 3-hydrazino-3-oxopropionate, (4-chlorobenzenesulphonyl)acetic acid hydrazide, 4-nitrophenylacetic acid hydrazide, phenylacetic acid hydrazide, thiophene-3-acetic acid hydrazide or indole-3-acetic acid hydrazide leads to the corresponding hydrazone derivatives. In the presence of sodium carbonate, these compounds react at room temperature with acetoacetanilide or 2,4-pentanedione to give the corresponding 1-aminopyrrole rings through the relevant 1,2-diaza-1,3-butadiene intermediates. In the presence of sodium methoxide, the activated methylene group present on the 1-amino side chain of the heterocycles obtained from ethyl 3-hydrazino-3-oxopropionate or 4-nitrophenylacetic acid hydrazide attacks at room temperature 1,2-diaza-1,3-butadienes affording the respective hydrazonic 1,4-adducts. Under basic conditions, these adducts cyclise at room temperature providing NHCOCH-bridged pyrrole–pyrazole systems. In the case of (4-chlorobenzenesulphonyl)acetic acid hydrazide, the corresponding 1-aminopyrrole does not add a further molecule of 1,2-diaza-1,3-butadiene giving rise to 1H-pyrrole and 2-oxohydrazone derivatives as identified compounds. Under the same reaction conditions, the NH group of 1-aminopyrroles derived from phenylacetic acid hydrazide, thiophene-3-acetic acid hydrazide or indole-3-acetic acid hydrazide adds at room temperature 1,2-diaza-1,3-butadienes producing another type of hydrazonic 1,4-adduct. Under basic conditions, these adducts cyclise at room temperature giving rise to different N-bonded pyrrole–pyrazole systems.

Synthesis and Immunotropic Activity of (Benzimidazolyl-2-thio)acetic Acid Derivatives Containing Thietane Cycles

In continuation of the search for immunotropic compounds among 1-(thietan-3-yl)benzimidazole derivatives [1], we have synthesized a series of new salts and hydrazides of (benzimidazolyl-2-thio)acetic acids containing thietane cycles. Reactions of 2-[1-(thietan-3-yl)(Ia) and 2-[1-(1,1-dioxothietan-3-yl)(Ib) benzimidazolyl-2-thio]acetic acids with bases (amino alcohols or sodium hydroxide) led to the corresponding salts IIa – IIh. Using ethyl esters IIIa and IIIb, obtained by reacting acids Ia and Ib with ethanol in the presence of sulfuric acid, we synthesized (benzimidazolyl-2-thio)acetic acid hydrazides IVa and IVb, respectively. For biological tests, hydrazides IVa and IVb were converted into dihydrochlorides Va and Vb, respectively.

New 6-Phenylimidazo[2,1-b]thiazole Derivatives: Synthesis and Antifungal Activity

New benzylidene-(6-phenylimidazo[2,1-b]thiazol-3-yl)-acetic acid hydrazides, 4-alkyl-1-((6-phenylimidazo[2,1-b]thiazol-3-yl)-acetyl)-3-thiosemicarbazides, 2-aryl-3-((6-phenylimidazo[2,1-b]thiazol-3-yl)-acetamido)-4-thiazolidinones, and 3-alkyl-2-(((6-phenylimidazo[2,1-b]thiazol-3-yl)-acetyl)-hydrazono)-4-thiazolidinones were synthesized from 6-phenylimidazo[2,1-b]thiazole-3-acetic acid hydrazide and evaluated for antifungal activity against three dermatophyte strains using ketoconazole as standard. Several of them were found as effective as the standard against Trichophyton rubrum and Microsporum audounii (MIC=6 μg/cm3), whereas the activity of N-benzylidene-(6-phenylimidazo[2,1-b]-thiazol-3-yl)-acetic acid hydrazide against M. audounii was superior to the standard (MIC=3 μg/cm3). 2-(4-Methylphenyl)-3-((6-phenylimidazo[2,1-b]thiazol-3-yl)-acetamido)-4-thiazolidinone and 2-(4-chlorophenyl)-3-((6-phenylimidazo[2,1-b]thiazol-3-yl)-acetamido)-4-thiazolidinone showed the highest activity against Trichophyton mentagrophytes var. erinacei NCPF-375 (MIC=3 μg/cm3).

SYNTHESIS OF 1,2,4 - TRIAZOLE, 1,2,4 - TRIAZOLO [3,4 -b] [1,3,4] THIADIAZOLE AND 1,2,4 -TRIAZOLO [3,4 -b] [1,3,4] THIADIAZINE DERIVATIVES OF 3- [5- (BENZOTHIAZOL - 2 - YL) THIENO [2,3-d] PYRIMIDINE - 4- ONE] ACETIC ACID HYDRAZIDE.

Article SYNTHESIS OF 1,2,4 - TRIAZOLE, 1,2,4 - TRIAZOLO [3,4 -b] [1,3,4] THIADIAZOLE AND 1,2,4 -TRIAZOLO [3,4 -b] [1,3,4] THIADIAZINE DERIVATIVES OF 3- [5- (BENZOTHIAZOL - 2 - YL) THIENO [2,3-d] PYRIMIDINE - 4- ONE] ACETIC ACID HYDRAZIDE. was published on October 1, 1999 in the journal Heterocyclic Communications (volume 5, issue 5).

Isoniazid inhibition of mycolic acid synthesis by cell extracts of sensitive and resistant strains of Mycobacterium aurum.

Isonicotinic acid hydrazide (isoniazid; INH) inhibition of mycolic acid synthesis was studied by using cell extracts from both INH-sensitive and -resistant strains of Mycobacterium aurum. The cell extract of the INH-sensitive strain was inhibited by INH, while the preparation from the INH-resistant strain was not. This showed that the INH resistance of mycolic acid synthesis was not due to a difference in drug uptake or the level of peroxidase activity (similar in both extracts). As INH did not induce accumulation of any labeled intermediates, it is postulated that the drug acts either on production of labeled chain elongation precursors of mycolic acids or an early step of this elongation. The level of inhibition was not changed by addition of NAD or nicotinamide; thus, INH does not act on mycolic acid synthesis as an NAD antimetabolite. Benzoic or acetic acid hydrazides and known or postulated metabolites of INH (i.e., the corresponding acid, aldehyde, or alcohol) were not inhibitors of cell-free mycolic acid synthesis; the complete structure of INH was required, as already known for inhibition of mycobacterial culture growth. Extracts prepared from INH-treated cells showed reduced mycolic acid synthesis, and the inhibition level was not modified by either extensive dialysis or pyridoxal phosphate. This latter molecule efficiently antagonized INH action by reacting rapidly with INH, as shown by differential spectroscopy. Moreover, pyridoxal phosphate did not release inhibition of INH-treated extracts. It is proposed that INH may covalently react with an essential component of the mycolic acid synthesis system.

Synthesis, physicochemical properties, and biological activity of (acridinyl-9-thio)acetic acid hydrazides

Synthesis, physicochemical properties, and biological activity of (acridinyl-9-thio)acetic acid hydrazides

ChemInform Abstract: A New Route for the Convenient Synthesis of 3‐(Thiazol‐2′‐ylthio)‐2H‐1‐benzopyran‐2‐ones.

Abstract Different thiazolylthiocoumarins were prepared by the reaction of (thiazol-2-ylthio) acetic acid hydrazides with 2-hydroxybenzaldehydes, followed by cyclization of the formed N-benzylidene derivatives in presence of PPA.

A new route for the convenient synthesis of 3-(thiazol-2'-ylthio)-2h-1-benzopyran-2-ones

Different thiazolylthiocoumarins were prepared by the reaction of (thiazol-2-ylthio) acetic acid hydrazides with 2-hydroxybenzaldehydes, followed by cyclization of the formed N-benzylidene derivatives in presence of PPA.

Synthesis of some new hydrazone derivatives as biologically active agents.

A series of [4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl)phenoxy]acetic acid (1,2-dihydro-1-H/methyl-2-oxo-3H-indol-3-ylidene)hydrazides (VII1-16) were synthesised by condensing 1-H/methyl-5-substituted indoline-2,3-diones with [4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl) phenoxy]acetic acid hydrazides (IV1-2) which in turn were obtained by reacting ethyl [4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl)phenoxy]acetates (III1-2) with hydrazine hydrate. All the synthesised compounds (VIII1-16) were screened for their antibacterial, acetylcholinesterase enzyme inhibitory and antiviral activities.

Reaktionen mit cyclischen Oxalylverbindungen, XXIV. Zur Reaktion von 4-Benzoyl-5-phenyl-furan-2,3-dion mit Phenylhydrazonen bzw. Phenylhydrazin

4-Benzoyl-5-phenyl-furan-2,3-dione (1) reacts with various phenylhydrazones2 at 60–80°C to the pyrazole carboxylic acid3 a, which then can be decarboxylated to 4-benzoyl-1,5-diphenyl-pyrazole (5).1 and phenylhydrazine combine again yielding3 a as the main product and the isomeric pyridazinone6 as by-product. At higher temperatures (120–140°C) the reaction of1 with2 a leads to the formation of dibenzoyl acetic acid hydrazide derivatives8.

Structure of trimethylsilyl derivatives of acetic acid hydrazides

The authors use NMR spectroscopy to study mono-and bistrimethylsilyl derivatives of N'-methyl- and N',N'-dimethylhydrazides of acetic acid. Two isomers in mobile equilibrium are found for both compounds in the temperature range from -80 to +100 C. It is shown that the trimethylsilylated N',N'-dimethylhydrazide of acetic acid is an equilibrium mixture of the syn and anti isomers of the hydrazone form, while the N,N'-bistrimethylsilyl-N'-methylhydrazide of acetic acid exists as an equilibrium mixture of N and O isomers.

Pyrene derivatives as fluorescent probes of conformation near the 3′ termini of polyribonucleotides

AbstractWhen pyrene butyric acid hydrazide or pyrene acetic acid hydrazide is attached to single‐strand RNA 3′ termini a red shift in absorbance and substantial hypochromicity are observed. A strong induced CD is seen and the fluorescence intensity is quenched by an order of magnitude. In double‐stranded samples, a further 10‐fold quenching of fluorescence is seen. Several lines of evidence suggest that the residual fluorescence of pyrene butyric acid hydrazide‐duplex conjugates arises from a minor species. The most likely possibility is dye reacted at a site other than the 3′ end. Some indication exists that 3′‐attached pyrene may perturb the relative stability of nearby duplex. Within the limits of this reservation, it appears that 3′‐pyrene conjugates may be rather useful for detecting the existence of duplex regions accessible to a dye at the 3′ end of complex RNAs.

Reactivity of methyl (3,6‐dichloropyridazin‐4‐yl)acetate towards nucleophiles

AbstractMethyl (3,6‐dichloropyridazin‐4‐yl)acetate (II), prepared from methyl (3,6‐dihydroxypyrid‐azin‐4‐yl)aeetate (1) by chlurination with phosphorus oxychloride, was used for studies of nucleo‐philic displacement reactions and it has been found that only the chlorine atom at position 6 was displaced with hydrazine. With diluted hydrochloric acid both chlorine atoms were displaced with the 6‐oxo isomer predominating. By turning the aromatic ring of pyridazine into an o‐quinoid system, the chlorine atom at position 3 became mobile. Cyelization of (6‐hydrazino‐s‐triazolo‐[4,3‐b ]pyridazin‐7‐yl)acetic acid hydrazide (XIX) gave 6‐aminopyrrolo[3,2‐e ]s‐triazlo[ 4,3‐b ]‐pyridazm‐7(8H)one (XXI).

Prophage induction in lysogenic Escherichia coli with simple hydroxylamine and hydrazine compounds.

The prophage-inducing capability of hydroxylamine sulfate and 36 of its derivatives, and of hydrazine dihydrochloride and dihydrazine sulfate and 43 of their derivatives, was determined in Escherichia coli W1709 (lambda). Maximal nontoxic concentrations up to 1 mg/ml were tested. Hydroxylamine sulfate was active at 2.5 mug/ml and the following 17 derivatives were active at concentrations ranging up to 500 mug/ml: alpha-naphthylhydroxylamine, N-hydroxy-2-aminofluorene, oxamyl hydroxamic acid, O-carbamoyl hydroxylamine (isohydroxyurea), N-hydroxyurethane, N-methylhydroxylamine HCl, salicylhydroxamic acid, oxalohydroxamic acid, methoxyamine HCl, ethoxyamine HCl, N, N-diethylhydroxylamine oxalate, formaldoxime, formamidoxime, acetohydroxamic acid, acetaldoxime, acetone oxime, and hydroxyguanidine sulfate. Hydrazine dihydrochloride and dihydrazine sulfate were effective inducers at 5.0 and 2.5 mug/ml, respectively, and the following nine derivatives of them were active at concentrations ranging up to 500 mug/ml: phthalic acid hydrazide, phenylhydrazine HCl, p-nitrophenylhydrazine, p-chlorophenylhydrazine HCl, formylhydrazine, carbohydrazide, semicarbazide HCl, 1-methyl-1-phenyl-hydrazine sulfate, and acetic acid hydrazide. Nineteen hydroxylamine and 34 hydrazine derivatives were ineffective as inducers. Application of the prophage-induction system as a tool for detection of responsive hydroxylamino and hydrazino compounds which may be potential toxicological hazards in the environment is discussed.

Prophage Induction in Lysogenic Escherichia coli with Simple Hydroxylamine and Hydrazine Compounds

The prophage-inducing capability of hydroxylamine sulfate and 36 of its derivatives, and of hydrazine dihydrochloride and dihydrazine sulfate and 43 of their derivatives, was determined in Escherichia coli W1709 (lambda). Maximal nontoxic concentrations up to 1 mg/ml were tested. Hydroxylamine sulfate was active at 2.5 mug/ml and the following 17 derivatives were active at concentrations ranging up to 500 mug/ml: alpha-naphthylhydroxylamine, N-hydroxy-2-aminofluorene, oxamyl hydroxamic acid, O-carbamoyl hydroxylamine (isohydroxyurea), N-hydroxyurethane, N-methylhydroxylamine HCl, salicylhydroxamic acid, oxalohydroxamic acid, methoxyamine HCl, ethoxyamine HCl, N, N-diethylhydroxylamine oxalate, formaldoxime, formamidoxime, acetohydroxamic acid, acetaldoxime, acetone oxime, and hydroxyguanidine sulfate. Hydrazine dihydrochloride and dihydrazine sulfate were effective inducers at 5.0 and 2.5 mug/ml, respectively, and the following nine derivatives of them were active at concentrations ranging up to 500 mug/ml: phthalic acid hydrazide, phenylhydrazine HCl, p-nitrophenylhydrazine, p-chlorophenylhydrazine HCl, formylhydrazine, carbohydrazide, semicarbazide HCl, 1-methyl-1-phenyl-hydrazine sulfate, and acetic acid hydrazide. Nineteen hydroxylamine and 34 hydrazine derivatives were ineffective as inducers. Application of the prophage-induction system as a tool for detection of responsive hydroxylamino and hydrazino compounds which may be potential toxicological hazards in the environment is discussed.

Reactions of 2‐acyl‐1,3‐indandiones with monosubstituted hydrazines and hydrazides

AbstractMethyl‐ and phenylhydrazines react with 2‐(diphenylacetyl)‐1,3‐indandione (1) to yield respectively the 1‐(methylhydrazone) and the 1‐(phenylhydrazone) of 2‐(diphenylacetyl)‐1,3‐indandione (2a and 2b). In comparison, acetic and benzoic acid hydrazides react with 1 to give respectively the α‐(acetylhydrazone) and the α‐(benzoylhydrazone) of 2‐(diphenylacetyl)‐1,3‐indandione (3a and 3b). Cyclization of 2a and 2b gives 2,3‐disubstituted indeno[1,2‐c]pyrazol‐4(2H)‐ones (7a and 7b). Cyclization of 3a and 3b, followed by methylation, gives 1‐methyl‐ and 2‐methyl‐3‐(diphenylmethyl)indeno[1,2‐c]pyrazol‐4(1 and 2H)‐ones (9a and 9b). 2‐Isovaleryl‐1,3‐indandione reacts with phenylhydrazine to give directly 3‐isobutyl‐1‐phenylindeno[1,2‐c]‐pyrazol‐4(1H)‐one (10).

Studies of transfer RNA tertiary structure by singlet-singlet energy transfer.

This distance between a base next to the anticodon of tRNA and the 3' CpCpA terminus of the molecule has been estimated by singlet-singlet energy transfer experiments. The energy donor was the Y base of unknown structure found in yeast tRNA(phe). Three different energy acceptors were used: acriflavine, proflavinyl acetic acid hydrazide, and 9-hydrazino acridine. These were attached to the periodate-oxidized 3' end of the tRNA. R(0)'s between 24 and 30 A were calculated for the three chromophore couples by assuming that the relative orientation of donor and acceptor is random. This assumption is supported by the consistency of the experimental results with all three acceptors and by studies of the fluorescence depolarization of Y. The energy transfer observed both by quenching of Y and enhanced activation of the acceptors is quite small, indicating that the anticodon is more than 40 A away from the amino acid accepting terminus. This places severe restrictions on the type of tertiary structure possible for tRNA.

抗ガン剤に関する研究 第8報

Condensation products of (2-bromo-4, 5-dimethoxyphenyl) acetic acid hydrazide and various carbonyl compounds were prepared and their anti-cancer activity was examined. Some anti-cancer effect was observed in the condensation product with isovanillin. The reaction of the above hydrazide with chloral or bromal in alcohol was found to result in dehydrazino reaction to form ethyl (2-bromo-4, 5-dimethoxyphenyl) acetate. The mechanism of this reaction is now being examined.

抗ガン剤に関する研究 第9報

Bromination of (3, 4-dimethoxyphenyl) acetic acid hydrazide was found to form, besides various compounds, 1, 2-bis [(2-bromo-4, 5-dimethoxyphenyl)acetyl] hydrazine.