Acenaphthen-5,6-dicarbonsäure-imid-derivate

Derivatives of 2H-Indeno[6,7,1-def]isoquinoline The synthesis of the derivatives 1a–1i of 1,3,6,7-tetrahydro-2H-indeno[6,7,1-def]isoquinoline-1,3-dione is reported. It was impossible to oxidize these compounds to the 1,3-dihydro derivatives 2a–2i . The carbocyclic analogue, 7-methoxy-5H-cyclopenta[ed]phenalen-5-one (5) , reacts with 2,4-dinitrophenylhydrazine to yield the hydrazone 6 .     

Heterocyclische 12-π- und 14-π-Molekülsysteme, 44. Mitt. Zum Reaktionsverhalten tetracyclischer Pseudohydroxyphenalenone

Heterocyclic Systems with 12 or 14 π Electrons, XLIV: Chemical Reactivity of Tetracyclic Hydroxypseudo-phenalenones 1,2-Dihydro-7-hydroxy-5H-cyclopenta[cd] phenalen-5-one (1) reacts with nitric acid in acetic acid to yield the hydroxy(nitro)pseudophenalenone 3 . With chlorine in acetic acid the dichloro derivative 4 , with bromine compound 5 , and with phenyldiazoniumsulfate the azodye 6 are formed. Compound 1 also reacts with 1,2-dibromoethane in the presence of potassium carbonate to yield the spiro compound 7 . The condensation of 1 with benzaldehyde in the presence of pyridine yields 8 . In an analogous way 5H-7-hydroxycyclopenta[cd]phenalene-5-one (2) was chlorinated to yield the dichloro derivative 9 . Compound 2 reacts with bromine at position 6 to yield compound 10 .     

The Biotransformation of 8-Chloro-6-phenyl-4H-s-triazolo[4, 3-a][1,4] benzodiazepine (D-40TA), a New Central Depressant,in Man,Dog and Rat

1. Metabolic studies of 8-chloro-6-phenyl-4H-^s-triazolo [4,3-a] [1,4] benzodiazepine (D—40TA) in man, dog and rat led to identification of the following metabolites: six hydroxylation products; 8-chloro-2,4-dihydro-6-phenyl-1H-s-triazolo[4,3-a] [1,4]benzodiazepin-1-one (I), 8-chloro-6-(4-hydroxyphenyl)-4H-s -triazolo[4,3-a][1,4]benzodiazepine (II), 8-chloro-6- (3-hydroxyphenyl)-4H-s-triazolo[4,3-a] [1,4] benzodiazepine (III), 8-chloro-4-hydroxy-6-phenyl-4H-s- triazolo[4,3-a][1,4]benzodiazepine (IV), 8-chloro-2,4-dihydro-6- (4-hydroxy-phenyl)-1H-s-triazolo[4,3-a] [1,4] benzodiazepin-1-one (V) and 8-chloro-2,4-dihydro-6-(3-hydroxyphenyl)- 1H-s- triazolo[4,3-a][1,4]benzodiazepin-1-one (VI); five ring-opened metabolites; 5-chloro-2-(4H-1,2,4-triazol-4-yl) -benzophenone (VII), 5-chloro-2- (2,3-dihydro-3-oxo- 4H -1,2,4- triazol-4-yl)benzophenone (VIII), 5-chloro-2- (2,3-dihydro-3-oxo-4H - 1,2,4-triazol-4-yl)-2-hydroxybenzophenone (IX), 5-chloro-2- (2,3-dihydro-3-oxo-4H-1,2,4-triazol-4-yl)-4'-hydroxybenzophenone (X) and 5-chloro-2-(3,5-dioxo-2,3,4,5-tetrahydro-1H-1,2,4-triazol-4-yl) benzophenone(XI).

2. In man, metabolites I, IV, VII and VIII are present as the free form in the urine, and I, II, IV and VIII are present as conjugates. In the dog, all the metabolites are present. The rat transforms the compound mainly to metabolites I, II, IV and V. None of the ring-opened metabolites are observed in the rat.     

Synthese von 7,12-Dihydro-indolo[3,2-d][1]benzazepin-6-(5H)-onen und 6,11-Dihydro-thieno-[3′,2′:2,3]azepino[4,5-b]indol-5(4H)-on

Synthesis of 7,12-Dihydro-indolo[3,2-d][1]benzazepin-6-(5H)-ones and 6,11-Dihydro-thieno-[3′,2′:2,3]azepino[4,5-b]indol-5(4H)-one The title compounds 4 and 6 were prepared by Fischer indole synthesis. 4a is substituted in 10-position by reaction with bromine in glacial acetic acid. A fast ring inversion is observed for the azepine ring in 4 and 6 .     

Synthesis of Some Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones as Potential Platelet Aggregation Inhibitors

Twenty new compounds having 2-methyl-6-benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-one ( 2a – d ) and 2-methyl-6-(α-aminobenzyl)thiazolo-[3,2-b]-1,2,4-triazole-5-ol ( 5 – 20 ) structures were synthesized. Their structures were confirmed by elemental and spectroscopic analysis and their platelet aggregation inhibitory activities were investigated.     

Anellierte Chinoline, 5. Mitt. 10-Hydroxy-10H-indolo[3,2-b]chinolin-5-oxid („Dioxychindolin”︁)

Fused Quinolines, V: 10-Hydroxy-10H-indolo[3,2-b]quinoline 5-Oxide (“Dioxyquindoline”) “Dioxyquindoline”, described by Fichter and Boehringer, is not 5, 11-Dihydro-10-hydroxy-10H-indolo[3,2-b]quinoline-11-one (2) but the title compound 4 .     

Anellierte Thiopyrone, 2. Mitt. Thiopyrano[3,2-b]indol-4(5H)-on- und Thiopyrano[2,3-b]indol-4(9H)-on-2-carbonsäuren

Fused Thiopyrones, II; 2-Carboxylic Acids of Thiopyrano [3,2-b]indol-4(5H)-one and Thiopyrano[2,3-b]indol-4(9H)-one 3-Indolylthiofumaric acids 2 are cyclized by polyphosphoric acid (PPA) to yield the isomeric title compounds 6 and 8 .     

Zur Totalsynthese des 5-Acetoxy-6-methoxykawains

Total Synthesis of 5-Acetoxy-6-methoxykawain The oxidation of 5-hydroxy-4-methoxy-6-trans-styryl-2H-pyran-2-one ( 6 ) by periodic acid in methanol gives rise to racem.-4,6-dimethoxy-6-trans-styryl-2,5-pyrandione ( 7 ). The yield is 35% Compound 7 is the key intermediate¹⁾ for the total synthesis of (5S, 6S)-(+)-acetoxy-4,6-dimethoxy-6-trans-styryl-5,6-dihydro-2H-pyran-2-one ( 1 ).     

Structure-activity relationships of acronycin

Contribution to the Structure-Activity Relationships of Acronycine. The synthesis of 1b , an azaanalogue of acronycine (1a) , is reported. The solubility of 1b in water is 15-times that of 1a . Screening tests with the transplantation tumor leukemia P388 showed 1b to be inactive, like 1a and noracronycine. 6-Hydroxy-3,3,12-trimethyl-3-12-dihydrochromeno[5,6-b][1,8]naphthyridin-7-one, 5-hydroxy-2,2,11-trimethyl-2,11-dihydrochromeno[7,6-b][1,8]naphthyridin-6-one and 6-hydroxy-3,3-dimethyl-3H-pyrano[2′,3′:7,8]chromeno[2,3-b]pyridin-7-one, which are structurally related to 1a , are also inactive.     

Derivatives of 3-aminothieno(2,3-d)pyrimidine and of 3-amino(1)benzothieno(2,3-d)pyrimidine (author's transl)]

Derivatives of 3-Aminothieno[2,3-d]pyrimidine and of 3-amino[1]benzothieno[2,3-d]pyrimidine Derivatives of 3-aminothieno[2,3-d]pyrimidin-4(3H)-one and of 3-amino-5,6,7,8-tetrahydro[1]-benzothieno[2,3-d]pyrimidin-4 (3H)-one, both carrying basic substituents at position 2 (general formulae I and II ), were synthesized in an one-step reaction from the corresponding 2-acylamino-thiophene-(or-benzo[b]thiophene)-3-carboxylates with hydrazine.     

Synthesis and antimicrobial activity of [6′-methyl-4′-methoxy-2-oxo-2H-[1]-benzopyran)-2″,4″-dihydro-[1″, 2″, 4″]-triazol-3″-one and 3″-phenyl-thiazolidin-4″-one-phenoxymethyl derivatives of dipyranoquinoline

A series of bioactive 3H,7H,8H,11H-9-[(5″-(6′-methyl-2-oxo-2H-[1]-4′-benzopyranoxy)-2″,4″-dihydro-[1″,2″,4″]-triazol-3″-one)methyl]-3,8,11-trioxo-dipyrano[2,3-f;2,3-c]quinoline (4) and 3H,7H,8H,11H-9-[(2′-(3″-phenyl-thiazolidin-4″-one)-phenoxymethyl]-3,8,11-trioxo-dipyrano[2,3-f;2,3-c]quinoline (7) analogs of 3H,7H,8H,11H-9-bromomethyl-3,8,11-trioxo-dipyrano[2,3-f;2,3-c]quinoline (1) have been synthesized and evaluated for their antibacterial activity against Gram-positive bacteria (S. aureus) and Gram-negative bacteria (S. typhi and E. coli). Pyranoquinolines with triazole and thiazolidine moieties exhibited promising antibacterial activity. The structures of all synthesised compounds were confirmed on the basis of analytical and spectral data.     

Synthesis of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones as potential antimicrobial agents

Synthesis of new derivatives of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one via reaction of 7-(4-bromophenyl)-1,2-dihydro-5-(4-fluorophenyl)-2-thioxopyrido[2,3-d] pyrimidin-4(3H)-one with hydrazonoyl chlorides or reaction of 2-hydrazino-pyrido[2,3-d]pyrimidin-4(3H)-one with different aldehydes followed by cyclization of the products. All the newly synthesized compounds were evaluated for their antimicrobial activities and also their minimum inhibitory concentration against most of test organisms was performed. Amongst the tested compounds displayed excellent activity against all the tested microorganisms except SR and PA.     

Synthese und Eigenschaften des 3-Hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]chinazolin-2-carbonitrils

Synthesis and Properties of 3-Hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]quinazoline-2-carbonitrile Anthranilic acid reacts with 2-chloro-5-cyano-4-hydroxypyrid-6-one (3) in glacial acetic acid to yield 3-hydroxy-1,10-dioxo-5,10-dihydro-1H-pyrido[2,1-b]quinazoline-2-carbonitrile (4) . When the reaction is carried out in DMF under Ullmann conditions, 2-(dimethylamino)-5-cyano-4-hydroxypyrid-6-one (5) forms as a by-product. The methylation of 3 with diazomethane affords 2-chloro-5-cyano-2-methoxy-N-methylpyrid-6-one (9) and 2-chloro-5-cynao-4,6-dimethoxypyridine (10) . Under similar conditions compound 4 undergoes an esterifying ring cleavage to furnish methyl 2-(5-cyano-4,6-dimethoxypyrid-2-ylamino)benzoate (7) .     

A Structured–Activity Relationship Study of Batracylin Analogues

A number of isoindolo[l ,2-b]quinazolines and some benzo[4,5]isoquinolino[l,2-b]quinazolines as structural modification analogues of the antitumor compound batracylin were synthesized and evaluated against HL-60 cell growth and in topoisomerase II-mediated DNA cleavage assays. Of the compounds studied, 10,12-dihydro-7,8-methy lenedioxyisoindolo[ 1,2-b] quinazolin-12(10H)-one (1d), 2-amino-10,12-dihydroisoindolo[l ,2-b]quinazolin- 12(10H)-one (1p), and 2-amino-7,8-methylenedioxy-10,12-dihydroisoindolo[l ,2-b]quinazolin-12(10H)-one (1ab) exhibited good inhibitory activities against HL-60 cell lines as well as induction of topo II-mediated DNA cleavage activities.     

Synthesis of new series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones for their bacterial and cyclin-dependent kinases (CDKs) inhibitory activities

Two series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones were designed, synthesised, and evaluated for their antibacterial activities and CDKs inhibitory activities. The pyridazine derivative: 6-phenyl-5-phenylhydrazono-2,3,4,5-tetrahydropyridazine-3,4-dione (3a) revealed activity against Staphylococcus aureus as Gram-positive bacteria while compound 2-(2-Ethoxyphenyl-5-Phenylpiperazinosulfonamido)-3H-pyrido[2,3-d]pyrimidin-4-one (13c) was showing moderate antifungal activity against Candida albicans.     

Untersuchungen an 1,3-Dicarbonylverbindungen, 25. Mitt. Pyrano[3,2-b]indol-4(5H)-on und 9-Chlor-1-oxo-1H-pyrrolo[1,2-a]indol-2-carbaldehyd

1,3-Dicarbonyl Compounds, XXV: Pyrano[3,2-b]indole-4(5H)-one and 9-Chloro-1-oxo-1H-pyrrolo[1,2-a]indole-2-carbaldehyde On treatment with POCl₃DMF the BF₂ chelate 2 , obtained from the 1,3-dicarbonyl compound 1 , yields the title substances 5 and 9 . Compound 5 is characterized by way of the thione 6 and the oxonol 7 , compound 9 by way of the 1,4-dihydropyridines 10 .     

2-(1H-Tetrazol-5-yl)-4,5-dihydroindeno[1,2-b]pyran-4-one

2-(1H-Tetrazol-5-yl)-4,5-dihydroindeno[1,2-b] pyran-4-one The synthesis of the title compound is described. Results of a study of the antiallergic activities of the bioisosteric heterocycles 8b und 8c are reported. Experiments to prepare 4-pyridones by O/N exchange are presented.     

Synthese und Eigenschaften 6-substituierter 4-Alkoxy-5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-one

Synthesis and Properties of 6-Substituted 4-Alkoxy-5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-ones Reactions of the N-alkoxy-2-(2-thienyl)glycolamides 1B with dicyclohexylcarbodiimide yield the 4-alkoxy-5,6-dihydro-4H-thieno[3,2-b]pyrrol-5-ones 2b . Acid catalyzed methanolysis of the tetrahydropyranyl group in 2B, Bk results in the formation of the bicyclic lactams 5 .     

Synthesis,Anti-Inflammatory,and Ulcerogenicity Studies of Novel Substituted and Fused Pyrazolo[3,4-d]pyrimidin-4-ones

In the present investigation, some new pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives (7–12) as well as fused pyrazolo[3′,4′:4,5]pyrimido[1,2-b]pyridazin-4(1H)-one (14–16) and 7,8,9,10-tetrahydropyrazolo[3′,4′:4,5]pyrimido[1,2-b]-cinnolin-4(1H)-one (17) ring systems were synthesized using the starting compound 5-amino-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (5). The structures of the newly synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR, mass spectroscopy, and elemental analysis. The theoretical calculation of their lipophilicity as C log P was performed. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw edema test in rats using indomethacin as the reference drug. Ulcer indices for the most active compounds were calculated. Seven compounds (10b, 11a–f) showed consistently good anti-inflammatory activity. In particular, 5-{[4-(4-bromophenyl)-3-(4-chlorophenyl)-1,3-thiazol-2(3H)-ylidene]amino}-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (11e) and its 3,4-bis(4-chlorophenyl) analog (11f) were found to be the most effective among the other derivatives, showing activity comparable to that of indomethacin with minimal ulcerogenic effects. Correlation of the biological data of the active compounds with their theoretically calculated C log P values revealed that lipophilicity influences the biological response.     

Umsetzung von 1,2-Dihydro-3-indazolon mit ω-Dialkylaminoalkylhalogeniden und α,ω-Dihalogenalkanen

Reaction of 1,2-Dihydro-3-indazolone with ω-Dialkylaminoalkyl Halides and α, ω-Dihalogenalkanes The reaction of the potassium salt of 1,2-dihydro-3-indazolone with ω-dialkylaminoalkyl halides in anhydrous dioxane leads to basic lactim ethers, which are analgesics. On the other hand two basic compounds are formed, when α, ω-dihalogenopropanes participiate. Compound 1 was identified as 3,4-dihydro-2H-[1,3]oxazino[2, 3-b]indazole and compound 2 as 2,3-dihydro-lH-pyrazolo[1,2-a]indazol-9-one. Compound 2 is reduced by LiAlH₄, to 2,3-dihydro-lH, 9H-pyrazolo[1, 2-a]indazole ( 5 ).