Receptor binding studies of soft anticholinergic agents

Retrometabolism‐Based Drug Design and Targeting

“…A number of such compounds derived from methylatropine (e.g., PcPATR_NA.Me 104a, 104b) [302,303] or glycopyrrolate (e.g., PcPOAGP_NA.Et 104c) [304][305][306][307][308][309] have been recently synthesized and tested. Several of them showed promising and stereospecific in vitro receptor-binding and in vivo mydriatic activities as well as some degree of and M 3 /M 2 muscarinic-receptor subtype-selectivity.…”

Retention Prediction Modeling of Ginsenosides on a Polyvinyl Alcohol-bonded Stationary Phase at Subambient Temperatures Using Multiple Linear Regression and Artificial Neural Network

“…46 Ovality is also an indicator of how close the molecule's geometry is to a sphere, a cylinder or a disk. 47 An Ov value of 1.0 means that the molecule is a perfect sphere. Cylindrical and disk-like molecules will have Ov values greater than and less than 1.0, respectively.…”

General Linearized Biexponential Model for QSAR Data Showing Bilinear-Type Distribution

“…The distribution coefficient of ionizable or permanently charged compounds was calculated by the QLogP software and by including a À3 Â 0.723 correction for primary amines compared to their neutral form and a À9 Â 0.723 contribution for quaternary ammonium compounds as described previously. [40][41][42] For the ionizable amines, experimental log D o/w values were also collected from the compilation by Hansch and co-workers 8 for verification of the predicted values. Anticholinergic activities are pA 2 values determined with the in vitro guinea pig ileum assay.…”

“…For example, the antimicrobial activity of straight-chain aliphatic amines (1-butanamine to 1-octadecanamine) against Rhinocladium beurmanni 32,38 and the antimicrobial activity of quaternary ammonium-containing L-carnitine double ester soft antimicrobials [RCOOCH(CH 2 COOR 0 )CH 2 -Nme 3 þ ] against Staphylococcus aureaus 39 are shown in Figures 6 and 7, respectively as a function of molecular volume V and the QLogP calculated log octanolwater distribution coefficient (log D o/w ), 41,42 which are linearly related (QLogP ¼ 0.032VÀ0.723N) and, hence, interchangeable on these congener series, where N, a hydrogen-bonding-related parameter, has a fixed value. Both data show bilinear behavior, but their maxima appear at considerably different V values.…”

“…8). Most of these compounds were designed using soft drug approaches, 87,88 and different structural series have been included that were designed based either on the soft analog approach (soft quaternary anticholinergics, 43 soft propantheline analogs 44 ) or on the inactive metabolite-based approach (phenylmalonic analogs, 42,45 -47 phenylsuccinic analogs, 48,49 phenylcyclopentyl atropine and glycopyrrolate analogs 42,50,51 ). For comparison (and to illustrate the generality of the approach), a structurally entirely unrelated 1,3-dioxolane series 52 with similarly determined pA 2 values has also been included.…”