Derek W. Nelson

Nucleophilic perfluoroalkylation of nitrones

Abstract New methods for perfluoroalkylation of carbon nitrogen double bonds have been developed. Addition of (trifluoromethyl)trimethylsilane (TMSCF 3 ) to α,N-diarylnitrones produced a series of α-(trifluoromethyl)-N-hydroxyl amines protected as their O-trimethylsilyl derivatives. An alternate procedure using pentafluoroethyllithium (F 5 C 2 Li) and chlorotrimethylsilane (TMSCl) afforded O-trimethylsilyl-α-(pentafluoroethyl)-N-hydroxyl amines.

Facile high yielding synthesis of symmetric esters of methylenebisphosphonic acid

Abstract The 1H-tetrazole catalyzed coupling of methylenebis(phosphonic dichloride), CH2(POCl2)2, with primary alkyl, cyclic secondary alkyl, aromatic, and silicon- and fluorine-containing alcohols selectively affords symmetric P,P′-dialkyl partial esters as well as homoleptic and mixed tetraesters. Two partial ester intermediates, methylenebis(2-ethylhexyl phosphonic chloride) and 2-ethylhexyl methylenebisphosphonic trichloride, were observed by 1H- and 31P NMR spectroscopy in the esterification of CH2(POCl2)2 with 2-ethyl-1-hexanol.

Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB 2 receptor agonists for pain management

SAR studies on a series of thiophene amide derivatives provided CB(2) receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB(2) over CB(1) effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB(2) antagonist demonstrated the efficacy in the pain models resulted from CB(2) agonism.

Synthesis and in vitro activity of N-benzyl-1-(2,3-dichlorophenyl)-1H-tetrazol-5-amine P2X7 antagonists

Synthesis and biological evaluation of a novel class of substituted N-benzyl-1-(2,3-dichlorophenyl)-1H-tetrazol-5-amine derivatives resulted in the identification of potent P2X(7) antagonists. These compounds were assayed for activity at both the human and rat P2X(7) receptors. On the benzyl moiety, a variety of functional groups were tolerated, including both electron-withdrawing and electron-donating substituents. Ortho-substitution on the benzyl group provided the greatest potency. The ortho-substituted analogs showed approximately 2.5-fold greater potency at human compared to rat P2X(7) receptors. Compounds 12 and 38 displayed hP2X(7)pIC(50)s>7.8 with less than 2-fold difference in potency at the rP2X(7).