Syntheses of Novel Pyridazinomorphinans by Inverse Electron Demand Cycloaddition and their Binding to μ and κ Receptors

A number of novel pyridazinomorphinans have been synthesized by the inverse electron demand Diels-Alder reaction of various 3,6-disubstituted 1,2,4,5-tetrazines with enamines derived from dihydrocodeinone and with codeinone. Reduction of some of the pyridazinomorphinans did not furnish the expected pyrroloepoxymorphinans; in all cases investigated reductive cleavage of the epoxybridge was observed to yield dihydropyridazino- or pyrrolomorphinans. The structures of all new compounds were assigned by the spectral data, that of the cycloadduct of codeinone was additionally verified by X-ray crystallography. Compounds 5a, 8, 11a , and 16 have been evaluated for their affinity at μ and κ opioid receptors in radioligand binding assays. Their ability to inhibit [³H]DAMGO binding at μ and [³H]U 69.593 binding at κ receptors, respectively as compared to codeine has been found to be lower.     

Treatment of iatrogenic biliary obstruction by balloon dilatation of a biliary jejunal fistula

Biliary obstruction and multiple hepatic abscesses occurred in a patient after ligation of a segmental branch of the right hepatic duct. The patient was successfully managed by transhepatic biliary drainage and balloon dilatation of an internal fistula that developed between the ligated duct and a Roux limb of jejunum. Internal biliary fistulas may be dilated using interventioanl radiologic techniques to permit nonobstructed bile flow. Implications for the nonsurgical treatment' of biliary strictures are discussed.     

Asymmetrische elektrophile α-Amidoalkylierung, 4. Mitt.: Erzeugung und Abfangreaktionen chiraler N-Acylpyrrolidiniumionen

Asymmetric Electrophilic α-Amidoalkylation, 4): Generation and Trapping Reactions of Chiral N- Acylpyrrolidiniumions The pyrrole derivatives 1 , 6 , and 10 react in the presence of TiCl₄ with the silyl enol ether 3 to form α-substituted pyrrolidine amides steroselectively. 6 and 10 (after HCl-addition = > 11 ) react even at ?78°C, the reaction of 10 exceeds that of 6 in yield and stereoselectivity.     

Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines,XXVI: Antiplatelet and Antithrombotic Effects of the Oligoamine RE 1492 in Combination with Standard and Future Antithrombotic Drugs

The combined effects of the oligoamine RE 1492 with the NO-donor RE 2047 or ASA, ticlopidine, pentoxifylline and BM 14515 were determined in vitro (Born-test and in vivo (rat thrombosis model). The effects in vitro were supra additive but over independent. In vivo all combinations showed over additive and over independent inhibition of thrombus formation. The best results were obtained with a combination of 10 mg/kg RE 1492C and 10 mg/kg RE 2047. It inhibited thrombus formation in arterioles (A) by 79 % and 36 % in venoles (V). The combined effect of RE 1492C and pentoxifylline 10 mg/kg each was 62% (A) or 32% (V), respectively.     

Multiple Infundibulocystic Basal Cell Carcinomas: Case Report of Unique Unilateral Presentation

BACKGROUND: Basal cell carcinoma shows a wide spectrum of clinical and histologic appearances. A distinct tumor variant with follicular infundibulocystic differentiation is recognized, and there are only a few reports on its clinical presentation and management. OBJECTIVE: To report a case of multiple infundibulocystic basal cell carcinomas with a unique unilateral presentation. METHODS: A clinical history was obtained. Photographs were taken, and punch biopsies were performed. RESULTS: An 83-year-old Caucasian female presented with multiple unilateral, asymptomatic, skin-colored, dome-shaped papules around the right mouth for 11 years without apparent change. Punch biopsies revealed findings typical of infundibulocystic basal cell carcinoma. CONCLUSIONS: A patient with clinically indolent multiple unilateral infundibulocystic basal cell carcinomas is described. Given the location of these multiple lesions, standard treatment modalities for basal cell carcinomas would have significant cosmetic and functional implications. A management approach with clinical follow-up and surgical intervention only for changing lesions is discussed.