摘要:

AbstractThe geometries, tautomerization energies, and dipole moments of the tautomeric species of the 2‐amino‐2‐oxazoline heterocycle were calculated with full geometry optimization using semiempirical (MNDO, AM1 and PM3) andab initio(RHF/6–31G) methods. The planar conformation of the amino form is well reproduced by the semiempirical and by theab initiomethods as compared with X‐ray structures in which this form is found. However the exocyclic nitrogen atom is pyramidalized in the semiempirical geometries whereas theab initiomethod reproduces a sp2hybridization state. The twisted conformation of the imino form is better reproduced by theab initiocalculation. All methods (semiempirical andab initio) show a stability energy value in favour of the amino tautomer of the neutral heterocycle. On the contrary, the dominant species of the charged heterocycle is the imino tautomer, protonated on the exocyclic nitrogen atom. Molecular electrostatic potential calculations confirmed this tendency. Finally the 3D‐lipophilicity profile of the heterocycle completed the investigation of the

ISSN:0365-6233    

DOI:10.1002/ardp.19973301202

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractA series of 2‐(anilino or 2,6‐dichloroanilino)‐1,5(6)‐disubstituted‐1H‐benzimidazoles (1–43) were prepared by reaction of several 2‐chloro‐ or 2‐chloromethyl‐1H‐benzimidazoles with aniline derivatives. The prepared compounds were screened for theirin vitroantibacterial and antifungal activities. Compounds2, 8, and9exhi

ISSN:0365-6233    

DOI:10.1002/ardp.19973301203

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractA series of 2‐substituted naphthazarin derivatives, 5,8‐dihydroxy‐1,4‐naphthoquinone (DHNQ) derivatives and 5,8‐dimethoxy‐1,4‐naphthoquinone (DMNQ) derivatives, were synthesized, and their cytotoxic activity against some cancer cell lines and antitumor action against S‐180 tumor were evaluated. In general, 2‐(1‐hydroxyalkyl)‐DHNQ derivatives showed a higher cytotoxicity than 2‐(1‐hydroxyalkyl)‐DMNQ derivatives, implying a predominent role of redox cycling rather than electrophilicity in cytotoxicity. 2‐(1‐Alkoxy‐4‐methylpentyl) or 2‐(1‐acyloxy‐4‐methylpentyl) derivatives were produced by alkylation or acylation at the C‐1′ position of 2‐(1‐hydroxy‐4‐methylpentyl)‐DHNQ or DMNQ derivatives. Although the cytotoxicity differed according to the size of the alkyl or acyl chain, alkylation or acylation at the C‐1′ position did not improve the cytotoxicity remarkably, and DHNQ derivatives were still more cytotoxic than DMNQ derivatives. Separately,in vivotesting showed that 2‐(1‐acyloxyalkyl)‐DHNQ derivatives or 2‐(1‐alkoxyalkyl)‐DHNQ derivatives expressed a higher antitumor action than 2‐(1‐hydroxyalkyl)‐DMNQ or ‐DHNQ derivatives in contrast to the cytotoxicity observations. The total size of two side chains at C‐1′ seemed to govern the antitumor activity, with 9 to 11 carbon atoms being optimal. Thus, it is suggested that the physical properties as well as the chemical reactivity are to be c

ISSN:0365-6233    

DOI:10.1002/ardp.19973301204

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractSome pyrazolo[3,4‐c]quinoline‐4‐ones1–14and pyrazolo[3,4‐c]‐quinoline‐1,4‐diones15–17were prepared and biologically evaluated for their binding at the benzodiazepine receptor (BZR) in rat cortical membranes. The moderate binding activity of1–5,7,9–10, 13is attributable to the lack of the optional proton acceptor at position‐1, while the inactivity of the 1,4‐dione derivatives15–17is due to the lack of the essential proton acceptor at position‐3. These conclusions confirm the validity of our

ISSN:0365-6233    

DOI:10.1002/ardp.19973301205

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractSome 1,2,4‐triazolo[4,3‐a]quinoxalines1–10, and 1,2,4‐triazino[4,3‐a]quinoxalines11–12were prepared and biologically evaluated for their binding at the benzodiazepine receptor (BZR) in rat cortical membranes. The BZR affinity of1–10demonstrates that the presence of a proton acceptor at position‐1 is important for the potency of a BZR ligand. On the other hand, the BZR inactivity of the 1,2,5‐trione derivatives11–12shows that the right collocation of the essential L2lipophilic substituent is of paramount importance for receptor

ISSN:0365-6233    

DOI:10.1002/ardp.19973301206

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractSeven arylazoamidoximes (3), six phenoxycarbonyl derivatives (4), and six 1,2,4‐oxadiazol‐5‐ones (5) have been prepared and their structure and purity established by spectroscopy and elemental analysis. In the EI mass spectra ready elimination of NO from the title amidoximes was observed. A new addition reaction of3awith hydrochloric acid to 4‐chlorophenylhydroazoamidoxime7is described. The compounds were tested for nitric oxide dependent biological properties, i.e. platelet aggregation, antithrombotic effects, and decrease in blood pressure. In arterioles of rats 5/19 compounds inhibited the formation of thrombi with a laser beam by ≥ 20% 2 h after oral administration of 60 mg/kg. Among these are three amidoximes (3a, 3e, 3f), one phenoxycarbonyl derivative (4a), and one oxadiazolone (5a). With the 4‐chlorophenylazoamidoxime3ca long lasting (24 h) decrease of blood pressure in spontaneously hypertensive rats was observed. Microsomal fractions of rat liver oxidize arylazoamidoximes and generate nitric oxide (e.g.3aand3b). NO was measured by the oxyhemoglobin assay. The influence of SOD, pretreatment of the rats with dexamethasone, as well as kinetic parameters were determined. Type3compounds, therefore, are a new class of NO donors. Type4and5compounds function as the

ISSN:0365-6233    

DOI:10.1002/ardp.19973301207

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThe synthesis of two series of derivatives containing the quinazolinone‐4 moiety is described. 3‐Amino‐2(1H)‐thioxo‐4(3H)‐quinazolinone (1) was subjected to reactions with halogenoketones and halogenoaldehydes, leading to the production of the corresponding ketones, aldehydes, Schiff bases, and 6‐oxo‐1,4,5‐thiadiazin[2,3‐b]quinazoline derivatives. Subsequently,1was condensed with selected α,β‐unsaturated carbonyl compounds, aldehydes, ketones, acid chlorides, and esters. The compounds were tested for their potential activity in a model of humoral and cellular immune response. The tests showed that the compounds exhibited differential immunotropic activities. Of particular interest is compound19, exhibiting a strong stimulatory activity with regard to cellular immune response and compound16exerting a strong inhibitory action in both types

ISSN:0365-6233    

DOI:10.1002/ardp.19973301208

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0365-6233    

DOI:10.1002/ardp.19973301201

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY