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P Nussbaumer

Publications and source records attributed to P Nussbaumer.

25 records · Page 2Linked to original sources
PubMed1994

Synthesis and structure-activity relationships of the novel homopropargylamine antimycotics.

Analogues of the antimycotic allylamine terbinafine were prepared in which the naphthalene and the tert-butyl-acetylene moieties were preserved, but the spacer between these two groups was varied, and the antifungal activity of the new compounds was evaluated. All modifications of the original spacer such as reduction of the double bond, switching the position of the nitrogen atom, shortening, and elongation resulted in decreased potencies with one exception: Compounds with the CH2NMeCH2CH2 group between the 1-naphthalene and the optionally substituted tert-butyl-acetylene function demonstrated high antifungal activity in vitro. The new homopropargylamine derivatives are more potent than terbinafine against Aspergillus fumigatus. The results support the hypothesis that two lipophilic domains linked by a spacer of appropriate length and a polar center at a defined position in the spacer are the general requirements for high activity of allylamine antimycotics.

Alkynes↗
PubMed1993

Synthesis and structure-activity relationships of naphthalene-substituted derivatives of the allylamine antimycotic terbinafine.

Derivatives of the allylamine antimycotic terbinafine (1) with varied substitution at the naphthalene ring system have been prepared, and their antifungal activity has been evaluated. In general, the potency is strongly dependent on the bulkiness of the substituent. Only hydrogen or in some cases fluorine are tolerated as substituents at positions 2-4 and 6-8 of the naphthalene moiety, whereas 5-substituents may be larger in size (F, Cl, Br, Me). Derivatives with fluorine at positions 3, 5, and 7 or chlorine at position 5 showed enhanced activity against yeasts relative to 1. This increase in sensitivity could be intensified by simultaneous introduction of two fluoro substituents at positions 5 and 7. Compound 7q demonstrated 8- to 16-fold improved potency against Aspergillus fumigatus, Candida albicans, and Candida parapsilosis.

Allylamine↗
PubMed1993

Synthesis and structure-activity relationships of phenyl-substituted benzylamine antimycotics: a novel benzylbenzylamine antifungal agent for systemic treatment.

Derivatives of the benzylamine antimycotics with an extra phenyl ring incorporated in the side chain have been prepared and their antifungal activity evaluated. The potency is strongly dependent on the distance between the two phenyl groups and the type of spacer. Linking the aryl rings with a quaternary carbon atom resulted in the identification of highly active compounds 7f and 12a, having a novel 4-benzylbenzylamine side chain. Compound 7f and its 7-benzo[b]thienyl analogue 12a show significantly enhanced efficacy, in particular against Candida albicans, and are among the most potent allyl/benzylamine antimycotics identified so far. Extended investigations with the benzylbenzylamine derivative 7f revealed that, in addition to the enhanced antimycotic profile, the compound is the first representative of the benzylamine antimycotics suitable for systemic treatment.

Alkylation↗
PubMed1991

Synthesis and structure-activity relationships of benzo[b]thienylallylamine antimycotics.

Benzo[b]thiophene analogues of the allylamine antimycotic terbinafine (2) bearing the side chain at various positions and optionally substituted by halogen have been prepared and their antifungal activity studied. Derivatives bearing the side chain at positions 3, 4, or 7 are bioequivalents of 2. Compounds containing the allylamine side chain at position 7, with a further substituent at position 3, showed significantly enhanced activity against Candida albicans, an effect which appears to be specifically linked only to this particular substitution pattern. 3-Chloro-7-benzo[b]thienyl derivative 7m was found to be the most potent allylamine antimycotic identified so far. In general, substituted benzo[b]thiophenes can be used not only as potential equivalents of naphthalene in bioactive compounds but also as a tool to selectively modify biological activities.

Allylamine↗
PubMed1988

Long-term outlook after atrial correction of transposition of great arteries.

Late results were reviewed in 220 survivors after atrial correction of transposition of the great arteries who were operated between 1964 and 1985. Senning's procedure and its various modifications have been used; all patients who survived 30 days after correction were included in this analysis. Average follow-up for the whole group was 10.3 years; 113 patients were observed for 10 years, 26 patients for 15 years, and 8 patients for 20 years. The actuarial survival rate for the whole group was 89% at 10 years, 87% at 15 years, 82% at 20 years. It was higher in simple than in complex transposition (92% versus 84% at 10 years). Sudden deaths (8 patients) and late heart failure (6 patients) were the principal causes of death, predominantly in the complex transposition group (10/13 deaths). Late survival was more common in the latter part of the study, with 95% of patients operated on after 1978 surviving 9 years as opposed to 84% of patients operated on earlier. Late reoperation was necessary in 18 patients (8%), with 12 reoperations occurring within 2 years after correction. Cumulative reoperation rate reached 11.7% after 10 years. Reoperations were more common in complex than in simple transposition (14% versus 6%, p less than 0.05). Late arrhythmias can occur after atrial correction, and the cumulative incidence of pacemaker implantations was 8% at 10 years. Most of the survivors are functionally free of symptoms (83% of the simple and 75% of the complex transposition group). Significant tricuspid valve incompetence was encountered in only three patients, with two valve reconstructions being possible. In summary, long-term outlook for survivors of atrial correction for transposition of the great arteries remains encouraging, although complex transposition does seem to engender more late problems. Atrial correction is still warranted in simple transposition, but close cardiological surveillance is necessary.

Actuarial Analysis↗
PubMedDate not supplied

Stimulation of MCF-7 breast cancer cell proliferation by estrone sulfate and dehydroepiandrosterone sulfate: inhibition by novel non-steroidal steroid sulfatase inhibitors.

Steroid sulfatase (STS) regulates the formation of active steroids from systemic precursors, such as estrone sulfate and dehydroepiandrosterone sulfate (DHEAS). In breast tissues, this pathway is a source for local production of estrogens, which support the growth of endocrine-dependent tumours. Therefore, inhibitors of STS could have therapeutic potential. In this study, we report on substituted chromenone sulfamates as a novel class of non-steroidal irreversible inhibitors of STS. The compounds are substantially more potent (6- to 80-fold) than previously described types of non-steroidal inhibitors when tested against purified STS. In MCF-7 breast cancer cells, they inhibit STS activity with IC(50) below 100 pM. Importantly, the compounds also potently block estrone sulfate-stimulated growth of MCF-7 cells, again with IC(50) below 100 pM. For one compound, we also observed a lack of any estrogenic effect at high concentrations (1 microM). We also demonstrate for the first time that STS inhibitors can block the DHEAS-stimulated growth of MCF-7 cells. Interestingly, this cannot be achieved with specific inhibitors of the aromatase, suggesting that stimulation of MCF-7 cell growth by DHEAS follows an aromatase-independent pathway. This gives further justification to consider steroid sulfatase inhibitors as potential drugs in the therapy of breast cancer.

Arylsulfatases↗