Acetamido Derivatives Research Articles

Oxidative and Bacterial Pathways in Metabolic Activation of Nitrated Polycyclic Aromatic Hydrocarbons

Abstract The relationship between the in vitro genotoxicity of nitrated polycyclic aromatic hydrocarbons (NO2PAH) and their potency in vivo hinges on the presence of appropriate metabolic activation capabilities. The Salmonella typhimurium plate incorporation assay was used to investigate the mutagenicity of model NO2PAH with variants of strain TA98 deficient or enriched in transacetylase enzymes. 1-Nitropyrene, 2-nitrofluoranthene and 3-nitrofluroanthene were all direct-acting, and more active in the transacetylase-enriched variant YG1024. The reduced amino and acetamido derivatives, in contrast to the parent compounds, required metabolism by Aroclor 1254-treated rat liver S9 to exhibit activity. Activity was nevertheless enhanced in YG1024, strongly implicating an N-acetoxy ester or a hydro-xamic acid rather than a hydroxylamine as proximate active species. Following administration of the NO2PAH to rats, the nitrofluoranthenes, in contrast to 1-nitropyrene, gave rise to direct-acting mutagens excreted i...

ChemInform Abstract: Tautomerism in Some Acetamido Derivatives of Nitrogen‐Containing Heterocycles: X‐Ray Structural Analysis of 2‐Amino and 2‐Imino Forms of Benzothiazole Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tautomerism in some acetamido derivatives of nitrogen-containing heterocycles: X-ray structural analysis of 2-amino and 2-imino forms of benzothiazole derivatives

Amide and acylimine derivatives of nitrogen-containing heterocycles have been investigated by X-ray diffraction and IR and UV–VIS spectroscopy. X-Ray crystal diffraction indicated that the product of the reaction between 2-aminobenzothiazole and α-chloropropionyl chloride is in the amide form, whereas the product of the reaction between 2-aminobenzothiazole and trichloroacetyl chloride is in the acylimine form. The UV–VIS spectroscopic data define the position of the tautomeric equilibrium; the previously reported quantitative method to evaluate the position of the tautomeric equilibrium without the direct use of parameters arising from fixed parents is suitable for the compounds considered. Medium polarity, electron-withdrawing power of the acyl group, acidity of the exocyclic N–H bond, and ring size and aromaticity of the heterocyclic moiety were the main starting points for investigating the tautomeric properties in potential prototropic systems.

Mutagenicity of nitro- and amino-substituted carbazoles in Salmonella typhimurium. : I. Monosubstituted derivatives of 9H-carbazole

Mononitro, monoamino and monoacetamido carbazoles were assayed for mutagenicity in Salmonella typhimurium strains TA1535, TA1538, TA1537, TA1977, TA98 and TA100, with and without the addition of S9 from phenobarbital-induced rat liver. The role of bacterial metabolism of the nitro group was also studied using the additional strains TA98NR and TA98/1, 8DNP 6. None of the compounds was active in TA1535, while only 2-nitrocarbazole and 3-nitrocarbazole presented a weak mutagenicity towards its pKM101 derivative, TA100. All four nitrocarbazole isomers were mutagenic for TA1538 and TA98, their activities decreasing in the order: 2-nitrocarbazole ≈ 3-nitrocarbazole > 1-nitrocarbazole > 4-nitrocarbazole. Direct-acting mutagenicities for TA1537 were lower than for TA1538, but varied in the same order. Nitro reduction was an important step of metabolic activation of nitrocarbazoles, as indicated by the dramatic reduction of activity with TA98NR, as compared to TA98. Results obtained with TA98/1,8DNP 6 showed that O-acetyltransferase was only partly required for the expression of mutagenic potency of these compounds. 2-Aminocarbazole was a weak direct-acting mutagen for TA1538 and TA98. Its activity was strongly increased in the presence of S9 mix, while 3-aminocarbazole became active in these conditions. The acetamido derivatives were consistently less mutagenic than their parent amines. These results show that nitrocarbazoles and aminocarbazoles behave as reactive frameshift mutagens, acting mainly through the formation of esterified hydroxylamines. The very low activity of 4-nitrocarbazole might be related to an orientation of the nitro group perpendicular to the aromatic ring.

A New Strategy for Solid‐Phase Synthesis of O‐Glycopeptides

By direct glycoside synthesis, activated glycosyl amino acids are accessible. They can be utilized in the solid-phase synthesis for the preparation of glycopeptides with 2-azido-2-deoxy-D-galactose residues. The transformation into the acetamido derivatives and the subsequent deblocking occur on the polymeric support. This method is quite powerful, as the synthesis of the pentaglycosidated octapeptide shown below proves.

Chemical and biochemical studies of 2-propynylpyrrolidine derivatives. Restricted-rotation analogs of N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5)

A series of optically pure 2-[substituted-3-aminopropynyl]pyrrolidine derivatives, which are restricted-rotation analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5, compound 1), have been prepared from d- and l-proline. The compounds when tested in a series of in vitro muscarinic assays [[3H]CD (cortex), [3H]QNB (cortex), [3H]PZ (cortex), [3H]QNB (heart), [3H]QNB + GppNHp (heart)] were found to have weaker muscarinic properties than compound 1. The decrease in affinity was attributed to the increased size of the molecule resulting from the addition of a methylene group to form the pyrrolidine ring. The use of optically active compounds provided a more detailed examination of the complex pharmacological effects of the flexible muscarinic agent 1. The R enantiomers in the acetamide derivatives 12b, 12d, and 12f had a 5-10-fold greater affinity for the muscarinic receptor than the corresponding S enantiomers. A 5-fold difference or less found in the (R)- and (S)-carbamate derivatives 9, 15, and 16 suggested close overlap of the two enantiomers in the receptor binding domain. The affinity differences found in the enantiomeric acetamido derivatives when compared to those of the carbamate analogues may be the result of limited rotation of the acetamido group.

Synthesis of pyrazolo[4′,3′:5,6]pyrazino[2,3‐c]pyrazoles and pyrazolo[4′,3′:5,6]pyrazino[2,3‐d]pyrimidines and their application to polyester fibres

Abstract4‐Nitroso‐1‐phenyl‐3‐methyl‐5‐aminopyrazole (1) was condensed with ethylcyanoacetate (2), malononitrile (4a) and 2‐cyanomethylbenzimidazole (4b) to yield 6‐hydroxy‐5‐cyano, 6‐amino‐5‐cyano and 6‐amino‐5‐(benzimidazol‐2‐yl)‐3‐methylpyrazolo [3,4‐b]pyrazines 3, 5a and 5b, respectively. 5‐Cyano‐6‐chloro derivative 6 obtained from 3 was converted to 3‐aminopyrazolo[4′,3′:5,6]pyrazino[2,3‐c]pyrazoles 8a and 8b by the treatment with hydrazin hydrate (7a) and phenylhydrazine (7b), respectively. Compound 5a was treated with formamide (9a), urea (9b) and thiourea (9c) to give 4‐aminopyrazolo[4′,3′:5,6]pyrazino[2′3′‐d]pyrimidines 10a–10c. With refluxing acetic anhydride compounds 8a, 8b and 10a gave corresponding acetamido derivatives 8c, 8d and 10d. Compound 5a was treated with ethylorthoformate (11), acetic anhydride (12) or benzoylchloride (13) to give fused benzimidazopyrazolo[4′,3′:5,6]pyrazino[2′,3′‐d]pyrimidines, viz., benzimidazol[1,2‐c]pyrazolo[4,3‐g]pteridines (14a–14c). Some of the compounds 8, 10 and 14 were applied to polyester as disperse dyes and their fastness properties were studied.

ChemInform Abstract: A New Method for the Synthesis of α‐Fluoro and α,α‐Difluoro Benzylic Ketones, Esters and Nitriles.

AbstractAnodic oxidation of the benzyl methyl ketones (I) in acetonitrile in the presence of fluoride gives mixtures of the α‐fluoro ketones (II) and the acetamido derivatives (III).

Synthesis, antimalarial activity, and quantitative structure-activity relationships of tebuquine and a series of related 5-[(7-chloro-4-quinolinyl)amino]-3-[(alkylamino)methyl] [1,1'-biphenyl]-2-ols and N omega-oxides.

A series of 5-[(7-chloro-4-quinolinyl)amino]-3-[(alkylamino)methyl] [1,1'-biphenyl]-2-ols and N omega-oxides was prepared from the substituted 1-phenyl-2-propanones proceeding through the 5-nitro[1,1'-biphenyl]-2-ols, the corresponding amino, and acetamido derivatives to the N-[5-[(alkylamino)methyl]-6-hydroxy[1,1'-biphenyl]-3-yl]acetamides and final condensation with 4,7-dichloroquinoline or the N-oxide. In a quantitative structure-activity relationship study first run on 28 and later expanded to 40 substituted phenyl analogues and their N omega-oxides, increasing antimalarial potency vs. Plasmodium berghei in mice was found to be correlated with decreasing size (sigma MR) and electron donation (sigma sigma) of the phenyl ring substituents. A significant correlation with N omega-oxidation could not be demonstrated. Initial high activity against P. berghei infections in mice led to expanded studies that demonstrated in addition excellent activity against resistant strains of parasite, activity in primate models, and pharmacokinetic properties apparently allowing protection against infection for extended periods of time even after oral administration. Such properties encourage the clinical trial of a member of this class in man.

The evaluation of mutagenicities of 19 structurally related aromatic amines and acetamides in Salmonella typhimurium TA98 and TA100

19 aromatic amines were assayed for mutagenicity using Salmonella typhimurium strains TA98 and TA100 with and without the addition of S9 from Aroclor-1254-induced rat liver. These included: naphthalenes (1-amino-, 1-acetamido-, 2-amino-, 2-acetamido-, 1-amino-4-nitro- and 2-amino-1-nitro-), biphenyls (2-amino-, 2-acetamido-, 4-amino- and 4-acetamido-), fluorenes (2-amino- and 2-acetamido-), anthracenes (1-amino-, 1-acetamido-, 2-amino- and 2-acetamido-), 3-aminofluoranthene, 1-aminopyrene and 6-aminochrysene. None of the compounds were mutagenic when tested without S9. With S9, 15 of 19 were mutagenic for TA98 and 16 of the 19 were mutagenic for TA100. Overall, 2-aminoanthracene was the most potent mutagen. When compared to the parent amines, the respective acetamido derivatives were consistently less mutagenic.

ChemInform Abstract: 2‐(ALKYLTHIO)PENEM‐3‐CARBOXYLIC ACIDS. III. SYNTHESIS OF 6‐ETHYLPENEMS

AbstractÜber mehrere Reaktionsstufen erhält man aus dem β‐Lactam (I) das β‐Lactam (IIa), das über die Zwischenprodukte (IIb)‐(IId) zum Penemsäureester (III) cyclisiert wird.

2-(Alkylthio)penem-3-carboxylic acids. III. Synthesis of 6-ethylpenems.

An N-protected derivative of 4-phenylthio-2-azetidinone (3b) was ethylated to give 3c, which was converted into the phosphorane 5d by the standard procedure. Intramolecular Wittig reaction of 5d afforded 6-ethylpenem esters 8a and 9a which were transformed via manipulation of the side chain to the amino acids 8d and 9d and subsequently to the acetamido derivatives 8e and 9e, which are 1-thia analogs of the antibiotic PS-5.

ChemInform Abstract: SYNTHESIS OF METHYL‐SUBSTITUTED THIAZOLE BASES WITH A CONDENSED FURAN, THIOPHENE, OR SELENOPHENE RING

AbstractAls Ausgangsmaterialien für Cyaninfarbstoffe, die auf ihre spektralen und photographischen Eigenschaften untersucht werden sollen, stellt man die Basen (IV), (VII), (XIV) und (XVII) her.

Synthesis of methyl-substituted thiazole bases with a condensed furan, thiophene, or selenophene ring

Methyl-substituted heterocyclic bases with a furan, thiophene, or selenophene ring condensed with a thiazole ring were synthesized by heating the appropriate o-bromo acetamido derivatives with phosphorus pentasulfide or by oxidation of thioacyl compounds with potassium ferricyanide in alkaline media.

The synthesis of adenine-substituted derivatives of NADP and their potential as active coenzymes and affinity adsorbents.

Alkylation of NADP+ with iodoacetic acid at pH 6.5 yielded N1‐carboxymethyl‐NADP+ which, following enzymic reduction, alkaline rearrangement and enzymic reoxidation, gave N6‐carboxy‐methyl‐NADP+. Condensation of these analogues with 1,6‐diaminohexane in the presence of a water‐soluble carbodiimide generated the N1 and N6N‐(6‐aminohexyl)‐acetamide derivatives of NADP+ respectively. The coenzymic activities of the N1 and N6 adenine‐substituted carboxymethyl and N‐(6‐aminohexyl)‐acetamido derivatives of NADP+ were tested with several NADP+‐dependent dehydrogenases. The carboxymethyl derivatives were more active (up to 145%) relative to un‐substituted NADP+ than the corresponding N‐(6‐aminohexyl)‐acetamido compounds (up to 10%).NADP+ ‐N6‐[N‐(6‐aminohexyl)‐acetamide] was coupled to a soluble dextran and to Sepharose 4B by the cyanogen bromide technique. The dextran‐bound derivative contained 85 μmol NADP+ analogue/g dry dextran and was reduced at approximately 35% the rate of native NADP+ with glucose‐6‐phosphate dehydrogenase. The dextran‐bound NADP+ cycled at a rate of about 30% relative to free NADP+ in a system comprising glucose‐6‐phosphate dehydrogenase and l‐glutamate dehydrogenase. Sepharose‐bound NADP+ proved to be an effective biospecific adsorbent for affinity chromatography and was competent for the resolution of a mixture of bovine albumin, lactate dehydrogenase and glucose‐6‐phosphate dehydrogenase. The latter was eluted almost quantitatively with a pulse of 0.5 mM NADP+.

Organic derivatives of tin V. Synthesis and reactions of alkyltin trialkoxides

Summary Alkyltin trialkoxides, RSn(OR′)3 (R = Et, n-Bu and R′= CH3, C2H5, i-C3H7, n-C4H9 and t-C4H9) have been synthesised from alkyltin trichlorides and the corresponding sodium alkoxide. Mixed derivatives of the type BuSnXn(OPr-i)3 (X = Cl, CH3CO2 and C2H5CO2) were obtained by exchange reactions. Reactions of butyltin triisopropoxide with protic reagents (e.g., H2O, (CH3)2C=NOH, o-HOC6H4OH, C6H5CH2NH2, NH2CH2CH2NH2, i-PrNHCOCH3, n-BuNHCOCH3, HCONH2 and CH3CONH2) have been studied. Dialkyltin acetamido derivatives have also been synthesised. IR and NMR spectra and molecular weights of the new products are reported and discussed.

Investigations on the chemistry of heparin V. Disaccharides obtained after partial hydrolysis

1. 1. The structure of the polysaccharide backbone of heparin was investigated by means of graded hydrolysis procedures. 2. 2. Desulfated acetamido heparin was partially hydrolyzed with acid and the products were fractionated on a cation exchange resin. This yielded glucosamine, disaccharides and a mixture of oligosaccharides. 3. 3. Two disaccharides were isolated as their acetamido derivatives. One of these was identified as 4-O-(2- acetamido-2-deoxy-α- d-glucopyranoside)- d-glucopyranosyl-uronic acid and the other as 4-O-( d-glucopyranosyluronic acid )-2- acetamido-2- deoxy- d-glucopyranose . 4. 4. These results indicate that heparin contains alternating 1,4-linked units of glucosamine and glucuronic acid.

Die Solvolyse von α‐Bromstyrolen Substitution am ungesättigten trigonalen Kohlenstoffatom

AbstractIn ‘80%’ ethanol the or‐bromostyrenes 5a‐5d undergo unimolecular solvolysis to the corresponding acetophenones. In addition to acetophenone, α‐bromostyrene itself yields a minor amount of phenylacetylene. The p‐amino, p‐methoxy and p‐ acetamido derivatives 5b‐5c react 108, 104 and 103 times as fast, respectively, as the unsubstituted compound 5a, the rates being insensitive to 1‐5 equivalents of triethyl‐ amine. Furthermore, 5a and 5c show electrophilic catalysis by silver ion. A two‐step ionisation mechanism involving a digonal carbonium ion (p‐R‐C6H4C=CH2)+ is thus indicated.

6-Chloro-8-Ethylquinoline and Some Derivatives.

A SEARCH of the literature revealed no information concerning 6-chloro-8-ethylquinoline and hence the preparation of it and some of its derivatives was undertaken. A comparison of the properties of such compounds with those of 6-chloro-8-methylquinoline and its derivatives as reported by Irving, Greene, Peterson, and Capps (3) as well as with those of 6-bromo-8-ethylquinoline as reported by Beasley, Brown and Capps (2) appeared to be of interest. 6-Chloro-8-ethylquinoline was prepared from 2-amino5-chloroethylbenzene by the modified Skraup method as reported by Altau and others ( I ) . The 2-amino-5-chloroethylbenzene was obtained from the chlorination of 2acetamidoethylbenzene, which in turn had been synthesized from ethylbenzene (1). A solution of 6-chloro-8-ethylquinoline in sulfuric acid (sp. gr. 1.84) was added to a solution of fuming nitric acid (sp. gr. 1.5) in sulfuric acid (sp. gr. 1.84) a t 0-5 prior to increasing the internal temperature to 60 and maintaining it for 30 minutes. The structure of the 6chloro-8-ethyl-5-nitroquinoline, thus obtained, was established by comparing its properties with those of an authentic sample as synthesized by a Skraup ring-closure upon 2-acetamido-4-nitro-5-chloroethylbenzene ( 1 ) . 6-Chloro-8-ethyl-1-methylquinolinium ethyl sulfate resulted when 6-chloro-8-ethylquinoline was heated with dimethyl sulfate a t 135-140. 6-Chloro-8-ethyl-1-methyl2-quinolone was obtained by the oxidation of the methylquinolinium salt with alkaline ferricyanide solution a t 60°-650. A mixture of phosphorus oxychloride and phosphorus pentachloride reacted with the quinolone, when heated in an oil bath a t 125-130, yielding 2,6-dichloro8-ethylquinoline, which was then hydrolyzed by heating with sulfuric acid (52.5 ml.; sp. gr. 1.84)-water (36 ml.) solution. 6-Chloro-8-ethyl-2-hydroxyquinoline was nitrated with a mixture of sulfuric acid (sp. gr. 1.84) and nitric acid (sp. gr. 1.42) under relatively mild conditions yielding 6-chloro8-ethyl-2-hydroxy-5-nitroquinoline. An authentic sample of 6-chloro-8-ethyl-2-hydroxy-5-nitroquinoline was prepared for comparison purposes from 6-chloro-8-ethyl-5-nitroquinoline via 6-chloro-8-ethyl-l-methyl-5-nitro-2-quinolone and 2,6-dichloro-8-ethyl-5-nitroquinoline. The 6-chloro-8ethyl-l-methyl-5-nitro-2-quinolone was prepared according to modifications of conditions reported by Beasley, Brown, and Capps (2) for reacting 6-brome-8-ethyl-5-nitroquinoline with dimethyl sulfate and then oxidizing with alkaline hydrogen peroxide. Reaction of the 6-chloro-8-ethyl-lmethyl-5-nitro-2-quinolone with a mixture of phosphorus oxychloride and phosphorus pentachloride, while being heated in an oil bath a t 125-130°, gave some 2,6-dichloro8-ethyl-5-nitroquinoline, which was hydrolyzed upon heating with sulfuric acid (50 ml.; sp. gr. 1.84)-water (25 ml.) solution to 6-chloro-8-ethyl-2-hydroxy-5-nitroquinoline. A dinitro derivative of 6-chloro-8-ethyl-2-hydroxyquinoline formed, along with an unseparated mixture, upon nitration under more stringent conditions, while using a mixture of fuming nitric acid (sp. gr. 1.5) and sulfuric acid (sp. gr. 1.84). No attempt was made establish the structure of this dinitro derivative: The 2,6-dichloro-8-ethyl-5-nitroquinoline, as obtained from 6-chloro-8-ethyl-5-nitroquinoline, also served as a reference compound for indicating the position taken by the nitro group during the nitration of 2,6-dichloro-8-ethylquinoline with a mixture of sulfuric and fuming nitric acid. 6-Chloro-8-ethyl-5-nitroquinoline and 2,6-dichloro-8ethyl-5-nitroquinoline were each reduced independently with hydrogen a t 40 p.s.i. pressure, in the presence of Raney nickel catalyst, to the corresponding amine. 6-Chloro-8-ethyl-5-nitroquinoline was reduced also with a mixture of stannous chloride and hydrochloric acid to 5-amino-6-chloro-8-ethylquinoline. Heating 5-amino-6-chloro-8-ethylquinoline and 5-amino2,6-dichloro-8-ethylquinoline under refluxing conditions with a solution of acetic anhydride and glacial acetic acid gave the corresponding acetamido derivatives. The benzoylation of 5-amino-6-chloro-8-ethylquinoline and 5-amino-2,6-dichloro-8-ethylquinoline under SchottenBaumann conditions ( 4 ) yielded the corresponding benzamido derivatives.