This report describes the preparation and characterization of two polymorphic forms of RG 12525, a leukotriene D4 (LTD4) antagonist. Polymorph I is prepared by recrystallization from methanol or titration of the sodium salt of RG 12525 with citric acid. Polymorph II is prepared by recrystallization from methanol or titration of the ammonium salt of RG 12525 with citric acid. The polymorphic system is enantiotropic, with pure form I melting at 154 degrees C, 3 deg less than the melting temperature of form II. Form I is thermodynamically more stable than form II at room temperature. These polymorphic forms are differentiated using microscopy, differential scanning calorimetry (DSC), infrared spectroscopy (IR), and powder X-ray diffraction (XRD) analysis. Solubility properties from 31 to 72 degrees C were determined to be similar for both forms. The calculated solubilities at 25 degrees C are 7.6 and 9.8 microM for forms I and II, respectively. The free energy change from form II to form I at 25 degrees C is -0.15 kcal/mol. Thermodynamic properties of the system are summarized using a schematic free energy diagram.

No abstract

Efficient Synthesis of AMP579, a Novel Adenosine A1/A2 Receptor Agonist.-A highly regioselective route to title adenosine agonist (X) is presented, involving the condensation of an alkylsulfonamide (II) with a pyridine synthon (III) as key step. The sulfonamide protecting group then effectively prevents undesired cyclization pathway during formation of the deazapurine ring (IX). Title compound (X) is obtained in 35% overall yield in 8 steps starting from amino alcohol (I). -(SLEDESKI, ADAM W.; KUBIAK, GREGORY G.; O'BRIEN, MICHAEL K.; POWERS, MATTHEW R.; POWNER, TORY H.; TRUESDALE, LARRY K.; J. Org. Chem. 65 (2000) 23, 8114-8118; Process Chem., Rhone-Poulenc Rorer, Collegeville, PA 19426, USA; EN)