Relationship of three-dimensional structure of muscarinic antagonists to antimuscarinic activity: structure of thiodeacylaprophen hydrochloride

C₂₀H₂₈NS⁺.Cl⁻, 2-(diethylamino)ethyl 1,1-diphenylethyl sulfide hydrochloride (thiodeacylaprophen hydrochloride), M_r = 349.9, orthorhombic, P2₁2₁2₁, a = 8.933 (2), b = 11.710 (3), c = 18.934 (4) Å, V= 1980.6 (7) ų, Z = 4, D_x = 1.173 g cm⁻³, Cu Kα = 1.54178 Å, μ = 26.70 cm⁻¹, F(000) = 752, room temperature, final R = 4.1% for 1417 reflections with . Thiodeacylaprophen crystallized as a tertiary amine hydrochloride salt. The S—C—C—N⁺ segment adopts a trans configuration as does one of the C_phenyl—C—S—C segments. A comparison of the structure of thiodeacylaprophen with the crystal structures of potent antimuscarinic agents suggests that the relatively weak antimuscarinic activity of thiodeacylaprophen compared to atropine and aprophen may be substantially due to the short intramolecular SN⁺ distance of 4.106 (6) Å. Other contributing structural factors may include the direction of the N⁺—H bond and restricted accessibility of the sulfur atom for interatomic interactions.

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