ABSTRACT
A 68-year-old woman presented to our hospital with unstable angina and was admitted for further evaluation. While hospitalized, she developed persistent angina with hypotension along with ST-segment elevation in leads V1-V2 along with lead aVR elevation on 12-lead electrocardiogram. Coronary angiography revealed diffuse multi-vessel coronary vasospasm most notably in the left anterior descending artery (LAD). Due to incomplete resolution of vasospasm with intracoronary verapamil and nitroglycerin, along with hemodynamic compromise requiring an intra-aortic balloon pump, percutaneous coronary intervention (PCI) of the LAD was performed. Clinical workup revealed hypereosinophlia and elevated IgE; diagnosis of eosinophilic granulomatosis with polyangiitis was confirmed with evidence of radiographic migratory pulmonary infiltrates and airway obstruction on spirometry. The patient had recurrent angina after PCI but her symptoms resolved fully after a course of corticosteroids. We attribute her refractory vasospastic angina to previously undiagnosed small/medium-vessel vasculitis.
ABSTRACT
A formal synthesis of (+/-)-roseophilin is described. Scandium(III)-catalyzed Nazarov cyclization of 2,5-disubstituted N-tosylpyrrole 19 gives a 5,5'-fused ketopyrrole, and ansa-bridge formation via pi-allyl palladium macrocyclization gives 21.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Catalysis , Crystallography, X-Ray , Cyclization , Heterocyclic Compounds, 3-Ring/chemical synthesis , Heterocyclic Compounds, 3-Ring/chemistry , Models, Molecular , Molecular Structure , Organometallic Compounds/chemistry , Pyrroles/chemical synthesis , Pyrroles/chemistry , Scandium/chemistry , StereoisomerismABSTRACT
Thirty-four spermidine (SPD) and spermine (SPM) derivatives with aromatic substituents were synthesized and tested as inhibitors of specific binding of the NMDA channel blocker [3H]MK-801 to membranes prepared from rat hippocampus and cerebral cortex. SPD and SPM derivatives with aromatic substituents at the primary amino groups were the most potent inhibitors (IC50 3.9-4.7 microM). These compounds most likely act directly at the NMDA ion channel, since 30 microM SPM had no pronounced influence on their inhibiting activities. SPD derivatives with aromatic substituents at the secondary amino group were either inactive or highly SPM-sensitive inhibitors (IC50 10-82 microM), depending on the size of the substituent. Our results support the hypothesis that an aromatic interaction site near the center of polyamine derivatives contributes to polyamine inverse agonism.
