A group of methyl 1,4-dihydro-2,6-dimethyl-4-(2-, 3-or 4-NHOH; 3-or 4-N=O)-phenyl-5-pyridinecarboxylates possessing a C-3 CO 2 Me or NO 2 substituent [compounds 58, 1012, below] were synthesized by reduction of the C-4 nitrophenyl precursors [14] to the corresponding phenylhydroxylamine [58] derivatives using 5% rhodium-on-charcoal with hydrazine hydrate as the hydrogen donor, followed by re-oxidation of the phenylhydroxylamine product [68] to the corresponding nitrosophenyl [1012] derivative using pyridinium chlorochromate. A series of 1,4-dihydro-2,6-dimethyl-4-(2-trifluoromethylphenyl)pyridines [2634] possessing CO 2 Me, COMe, CONH 2 , P(=O)OEt 2 , CN, NO 2 C-3/C-5 substituents were synthesized using a modified Hantzsch reaction involving the condensation of 2trifluoromethylbenzaldehyde [17] with an aminocrotonate [1820] and a ketone [2125] derivative. In vitro calcium channel (CC) activities were determined using a muscarinic-receptor-mediated Ca +2 -dependent contraction of guinea pig ileal longitudinal smooth muscle assay. This class of compounds [58, 10 12, 2634] exhibited weak CC antagonist activity [10 -4 to 10 -7 M range] relative to the reference drug nifedipine [IC 50 = 1.4 × 10 -8 M]. Structure-activity relationships [SARs] acquired were in agreement with known SARs where the relative potency order for C-4 phenyl substituents is ortho and meta > para. A C-3 nitro substituent decreased CC antagonist activity. Compounds 2934 possessing C-3 CN or NO 2 , and a C-5 CO 2 Me, NO 2 , CONH 2 , COMe, or P(=O)OEt 2 , substituents exhibited weak CC antagonist activity in the 10 -4 to 10 -5 M range. Although this group of highly functionalized 1,4-dihydropyridines are not useful CC antagonists, they will serve as valuable model compounds to study the structure-function relationships of CC modulation.