Showing papers on "Pyrazole published in 1979"

3-Substituted pyrazole derivatives as inhibitors and inactivators of liver alcohol dehydrogenase.

Abstract: 3-Substituted pyrazoles, HOCH2 (1), HOCH2CH2 (2), HOCH2CH2CH2 (3), ClCH2 (4), ClCH2CH2 (5), ClCH2CH2CH2 (6), and CH3CO (7), were synthesized and evaluated in vitro on horse liver alcohol dehydrogenase for their potential as inhibitors of ethanol metabolism. 1 to 6 bound to the enzyme-NAD+ complex with dissociation constants of 40 to 200 microM, much higher than the constants for the corresponding 4-substituted pyrazoles, but with the same absorption maximum at 295 nm. 4 inactivated the enzyme within a few minutes, but NAD+ protected against reaction, and 4 nonspecifically alkylated many sulfur atoms in the protein. The isomer, 4-(chloromethyl)pyrazole, behaved similarly, 5 and 6 strongly inhibited the enzyme in the presence of NAD+, due to formation of the slowly dissociable (10(-3)s-1) enzyme-NAD+-pyrazole complex, but did not irreversibly inactivate the enzyme. 7 inhibits the enzyme weakly (Kp = 5 mM). It appears that the 3-substituted pyrazoles bind to the enzyme-NAD+ complex with the reactive functional group improperly positioned for specific irreversible reaction.

Silyl‐Derivate von Pyrazol, Isoxazol und 1,2,3‐Triazol

Abstract: 1,4-Bis(trimethylsilyl)-1,3-butadiin (1) wird durch Addition von Hydrazin (2) in 3(5)-(Trimethyl-silylmethyl)pyrazol (4a) ubergefuhrt. Bei der Reaktion von 1 mit Methylhydrazin (3) entstehen 1-Methyl-5-(trimethylsilylmethyl)pyrazol(4b)und l-Methyl-3-(trimethylsilylmethyl)pyrazol(5).—Durch Umsetzung von Hydroxylamin mit 1 in Ethanol bildet sich 5-(Trimethylsilylmethyl)isoxazol (6), wahrend in Pyridin neben 6 noch 3-Methyl-5-(trimethylsilyl)isoxazol (7) auftritt. Die 5-(Trimethylsilyl)isoxazole 7 und 10a–e konnen auch durch Einwirkung von Hydroxylamin auf die Acyl(trimethylsilyl)acetylene8a–f synthetisiert werden. Die Verbindungen 8a–f geben mit freier Stickstoffwasserstoffsaure die 4-Acyl-5-(trimethylsilyl)-1.2,3-triazole 12a–f. Silyl Derivatives of Pyrazole, Isoxazole and 1,2,3-Triazole The addition of 1,4-bis(trimethylsilyl)1,3-butadiyne (1) to hydrazine (2) affords 3(5)-(trimethylsilylmethyl)pyrazole (4a). The reaction of 1 with methylhydrazine leads to 1-methyl-5-(trimethylsilylmethyl)pyrazole (4b) and 1-methyl-3-(trimethylsilylmethyl)pyrazole (5). 1 and hydroxylamine (3) in ethanol give 5-(trimethylsilylmethyl)isoxazole (6); in pyridine 6 and 3-methyl-5-(trimethylsilyl) isoxazole (7) are formed. The 5-(trimethylsilyl)isoxazoles 7 and 10a–e can be synthesized by reaction of hydroxylamine with the acyl(trimethylsilyl)acetylenes 8a–f. Compounds 8a–f react with hydrazoic acid to form the4-acyl-5-(trimethylsilyl)-1,2,3-triazoles 12a–f.

Synthese und Reaktionen carbocyclischer Acyl‐keten‐S,S‐acetale

Abstract: Synthesis and Reactions of Carbocyclic Acyl-ketene-S,S-acetales Cyclohexanone, tetralone(1) and indanone(1) react with CS2 in the presence of bases and after methylation to 2-[bis(methylthio)-methyliden]-cyclohexanones 1,4-tetralones(1) 2,5 and -indanones(1) 3,6. In some cases thiophenes 8 and 9 are formed. The dimethyl-S,S-acetales 1, 2a and 3a react with mono or dinucleophiles to S,N- or N,N-acetales, with hydrazines to indazolone 22 or the pyrazole 23. Oxidation with H2O2 yield disulfones 25 and 27. The structure of products are determined by ir- and 1H-n.m.r.-spectroscopy.

Pyrazoles and pyrazolo[3,4-d]pyrimidines as biologically active agents.

Abstract: Syntheses of the pyrazole derivatives 2a-c by different routes and cyclisation of the products to pyrazolo [3,4-d] pyrimidines are reported. The structures of the compounds were confirmed by spectroscopy. A few of them were screened as pesticides. Pyrazole und Pyrazolo [3,4-d]pyrimidine als biologisch aktive Verbindungen Es wird uber die Synthese der Pyrazolderivate 2a-c auf verschiedenen Wegen und ihre Zyklisierung zu Pyrazolo[3,4-d]pyrimidinen berichtet. Die Struktur der Verbindungen wird durch Spektroskopie abgesichert, einige werden auf pestizide Wirkung getestet.

Studies on the chemical reactivity and the physical properties of allopurinol (pyrazolo[3,4-d]pyrimidin-4-one) and related compounds

Abstract: Pyrazolo [3,4-d]pyrimidines resemble purines by avoiding disubstitution at the peri-positions 1 and 7, but they also resist 1,2-disubstitution in the pyrazole ring. INDO calculations show that 1,2-disubstituted derivatives of allopurinol are the least stable.The anion of allopurinol is present as a mixture of tautomeric forms and yields upon methylation 1,5-, 2,5-, and 2,7-dimethyl derivatives. Alkylation of 4-methylthiopyrazolo[3,4-d]pyrimidine, either as the neutral molecule or as the anion, offers a convenient approach to the synthesis of many mono- and di-methyl derivatives, which serve as precursors for methylated allopurinols.

C-nucleoside studies. Part 8. Synthesis of 3-β-D-arabinofuranosylpyrazole from D-mannose

Abstract: Treatment of 3(5)-(1,2 :4,5-di-O-isopropylidene-D-manno-pentahydroxypentyl)pyrazole (6) with acetone and concentrated sulphuric acid caused isomerisation to 3(5)–(2,3:4,5-di-O-isopropylidene-D-manno-pentahydroxypentyl)pyrazole (10). Reaction with 1-fluoro-2,4-dinitrobenzene and triethylamine, and subsequent treatment with methanesulphonyl chloride afforded 1-(2,4-dinitrophenyl)-3-(1-O-methylsulphonyl-2,3 :4,5-di-O-isopropylidene-D-manno-pentahydroxypentyl)pyrazole (14) in 71% overall yield. On treatment with dilute hydrochloric acid in dioxan, or, preferably, with boron trichloride in dichloromethane followed by methanolysis, (14) afforded 1-(2,4-dinitrophenyl)-3-(β-D-arabinofuranosyl)pyrazole (16) in up to 58% yield. Treatment of dinitrophenyl derivative (16) with methanolic ammonia gave an 86% yield of 3(5)-β-D-arabinofuranosylpyrazole (2).

4-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1-(2-pyridinyl)-1H-pyrazole

Abstract: 4-(Aryloxyalkyl)pyrazoles of the formula ##STR1## useful as antiviral agents, are prepared by reacting the corresponding diketones of the formula Ar-O-Alk-CH(COR')COR" with hydrazine or a substituted hydrazine H 2 NNHR. Mono- or bis-pyrazoles are similarly obtained from bis-diketones of the formula ##STR2##

4-[6-(2-Chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1-[4-(4-morpholinyl)-1-oxobutyl]-1H-pyrazole

Abstract: 4-(Aryloxyalkyl)pyrazoles of the formula ##STR1## useful as antiviral agents, are prepared by reacting the corresponding diketones of the formula Ar--O--Alk--CH(COR')COR" with hydrazine or a substituted hydrazine H2 NNHR. Mono- or bis-pyrazoles are similarly obtained from bis-diketones of the formula ##STR2##

1-Aryl-4-aryl:sulphonyl-3-amino-propoxy-1H-pyrazole derivs. - hypolipaemics and hypocholesterolaemics of low toxicity and non-ulcerogenic

Abstract: 1-Aryl-4-arylsulphonyl-3-aminopropoxy -1H-pyrazole derivs. of formula (I) and their salts are new: (where R1 is H, halogen, 1-3C alkyl or alkoxy or CF3- gp. in meta or para position; R2, R3, R4 are H, halogen, 1-3C alkyl or alkoxy or CF3-; R5, R6 are each H or lower alkyl or together, and with the N atom to which they are attached, form a 5- or 6-membered heterocycle (piperidine or pyrrolidine) opt. contg. another heteroatom such as O (morpholine). (I) have hypolipaemic and hypocholesterolaemic properties. Suitable daily doses are 0.3-0.15 g, split up into two or three doses per 24 hrs. Even in amounts far greater than this (20-30 mg/kg) (I), eg. 4-gamma-(p-chlorophenylsulphonyl)-3-dimethylaminopropoxy-1-phenyl- -1H-pyrazole (I') affects neither the CNS nor the cardiac/circulatory and respiratory system, and is non-ulcerogenic. (I) are of low toxicity e.g. LD50 for mice is 125 mg/kg i.p. and 670 mg/kg p.o.

5-Phenyl-pyrazole derivatives and their salts, processes for their preparation and medicines containing them

Abstract: The 5-phenylpyrazole derivatives which have the formula in which R and R are a hydrogen or chlorine atom or a trifluoromethyl group, R is a hydrogen atom or a phenyl, benzyl or lower alkyl radical, R is a hydrogen atom or a methyl radical, R is a lower alkyl radical and A is carboxyl, alkoxycarbonyl, cyano and optionally substituted aminocarbonyl, have good lipid-lowering properties. They are suitable as long-term therapeutics because no liver changes occur. The corresponding 3-phenyl-5-pyrazolinones are suitable as starting materials for the preparation of these compounds.

Influence of pyrazole, an inhibitor of alcohol dehydrogenase on the prenatal toxicity of ethanol in the rat.

Abstract: Pyrazole, a potent inhibitor of alcohol dehydrogenase, induced a high incidence of ocular and urinary bladder anomalies in the offspring of rats following treatment on gestational day 9. A single moderate dose of ethanol potentiated the teratogenic action of pyrazole, but alone did not affect embryonic development.

Alkylating nucleosides. 2. Synthesis and cytostatic activity of bromomethylpyrazole and pyrazole nitrogen mustard nucleosides.

Abstract: Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucleosides 5 and 7, respectively. In some cases, the positional isomers 6 and 8 were also obtained. Treatment of 5 and 7 with methanolic ammonia gave the deprotected 3-(aminomethyl)pyrazole-5-carboxamide nucleosides 9. Reaction of 3--5 and 7 with bis(2-chloroethyl)amine led to the corresponding pyrazole nitrogen mustards 10--13. All the bromomethylpyrazole nucleosides described showed significant cytostatic activity against HeLa cell cultures.

Anil-Synthese. 19. Mitteilung†. Über die Herstellung von Stilbenyl-Derivaten des Isoxazols

Abstract: Preparation of Stilbenyl Derivatives of Pyrazoles Schiffs bases derived from 1-, 3- and 5-(p-formylphenyl)phenylpyrazoles and p-chloroaniline are reacted with various p-tolyl substituted aromatic heterocycles in the presence of dimethylformamide and potassium hydroxide or potassium t-butoxide to yield the corresponding heterocyclic substituted stilbenes (anil synthesis) Introduction of a chloro substituent in the 4- and 4,5-positions of the pyrazole system causes a decrease in yield and a hypsochromic shift in the absorption and fluorescence maxima of the title compounds

Reactions with Cyclic Amidenes III: Synthesis of Some New Fused Pyrazole Derivatives

Abstract: Abstract Diazotised 5-amino-3-hydroxy-4-phenylazopyrazole (1 a) and 3,5-diamino-4-phenylazo-pyrazole(1 b) coupled with active methylene reagents to yield the pyrazolo[1,5-c]-as-triazine derivatives (3a, b-5 a, b). On the other hand coupling of diazotised 1 a, with β-naphthal has afforded the acyclic azo derivative(6). Whereas diazotised 1 a underwent intramolecular cyclisation into the pyrazolo[1,5-c]-1,2,3,4-tetrazine derivative (3)on attemptet addition to acrylonitrile, diazotised 1 b reacted with acrylonitrile under the same conditions to yield the pyrazolo[1,5-c]-pyridazine derivative (4). Compounds 1 a, b reacted with benzoylisothiocyanate to yield the pyrazol-5-ylthiourea derivatives (10 a, b). Where as 10 a readily cyclised into the pyrazolo[3,4-c]-as-triazine derivative (11) on refluxing with pyridine, compound 10 b hydrolysed under the same conditions into the pyrazol-5-ylthiourea derivative (12).

Some aspects of the chemistry of 6,7,8,9-tetrahydro-3-hydroxy-2-methoxybenzocycloheptan-5-one

Abstract: 6,7,8,9-Tetrahydro-3-hydroxy-2-methoxybenzocyclohepten-5-one has been converted into several bromoderivatives, acetals, and esters, and into 3-hydroxy-2-methoxybenzocyclohepten-5-one; further, its reduction with LiAlH4 has been compared with that of 6,7-dihydro-3-hydroxy-2-methoxybenzocyclohepten-5-one. A synthesis of 6,7-dihydro-3-hydroxy-8-hydroxycarbonyl-2-methoxybenzocyclohepten-5-one has been developed. Synthesis of 6,7,8,9-tetrahydro-4-methoxy-10H-cyclohepta[e]benzofuran-10-ones, 9-hydroxy-5,6-dihydro-8-methoxy-4H-benzo[6,7]cyclohept[1,2-c]pyrazole, 5,6-dihydro-9-hydroxy-8-methoxy-4H-benzo[3,4]cyclohept[1,2-d]isoxazole, and 10-hydroxy-6,7-dihydro-9-methoxybenzo[5,6]cyclohept[1,2-b]indole are described.

Cycloadditions to methyl 3,3-dimethyl-3H-pyrazole-5-carboxylate

Abstract: Cycloadditions of diazoalkanes, 1-diethylaminopropyne, and diphenylketen to the title compound and the dimerization of the latter are reported.

Process for the preparation of 1-alkyl-3-aryl-4-pyrazolecarboxylates

Abstract: This invention relates to a process for preparing pyrazole carboxylates having the formula ##STR1##

Synthesis and antileukemic activities of furanyl, pyranyl, and ribosyl derivatives of 4-(3,3-dimethyl-1-triazeno)imidazole-5-carboxamide and 3-(3,3-dimethyl-1-triazeno)pyrazole-4-carboxamide.

Abstract: From the reaction of silylated 4-(3,3-dimethyl-1-triazeno)imidazole-5-carboxamide (DTIC, 5) and 3-(3,3-dimethyl-1-triazeno)pyrazole-4-carboxamide (DTPC, 9) with 2-chlorotetrahydrofuran, we have isolated in both cases a single tetrahydrofuran-2-yl derivative. However, when silylated DTPC was reacted with 2-chlorotetrahydropyran, two tetrahydropyran-2-yl compounds were obtained, and these were shown to be positional isomers on the basis of 1H NMR and UV data. These furanyl and pyranyl derivatives were tested for antileukemic activity (L-1210, in vivo) and the results were compared with the results obtained for the corresponding ribosyl derivatives of DTIC and DTPC.

Binuclear palladium complexes of 3,5-disubstituted pyrazoles

Abstract: A series of binuclear palladium 3,5-disubstituted pyrazole complexes of the general formulation [(CH3−nXnCO2)(pzH)Pd(µ-pz)]2 where pz = 3,5-dimethyl or 3,5-diphenylpyrazole, X = F, Cl, Br, C6H5, n ...