Structural Studies of Histamine H1 Effector Molecules: The Crystal Structure of the Antihistamine Drug (+)-Chlorpheniramine Maleate; [(+)-S-1-(p-Chlorophenyl)-1-(2-pyridyl)-3-N,N-dimethylpropylamine maleate]

Abstract

CuK. radiation to 28 = 128". The structure was solved and refined to R = 0.050 and w R = 0.066. The absolute configuration is confirmed as being S. The alkylamine chain is asymnletrically disposed to the two aryl rings, the p-chlorophenyl ring being more exposed a n d the 2-pyridyl ring partially occluded. The molecule has an open side to which both hydrogen bond and n orbital overlap linkages can occur. The maleate mono-anion is hydrogen bonded to the dimethylamino group via a normal N-H.

Neutron diffraction study of sodium hydrogen maleate trihydrate, NaH[C4H2O4].3H2O, at 120 K

“…In fact when one shifts the hydrogen from the original donor to the original acceptor one passes the symmetrical form. X-ray and neutrondiffraction determinations of potassium hydrogen maleate and maleic acid show the heavy-atom backbone to be symmetrical (Darlow & Cochran, 1961;James & Williams, 1974), consistent with symmetrical hydrogen bonding. NMR measurements (Gunnarsson, Wennerstr6m, Egan & Fors~n, 1976;Altman, Laungani, Gunnarsson, Wennerstr6m & Fors6n, 1978) also favour symmetrical bonding.…”

“…The same situation is also found in other acid maleates: the mean value for the above angles is 130.5 (10) ° in the compounds studied previously and listed in Table 2. In contrast, when no intramolecular hydrogen bond is formed, as in Li2 maleate.2H20 and Na 2 maleate.H20 (Town & Small, 1973;James & Williams, 1974) one of the carboxylate ions is considerably twisted out of the plane (by 81.4 and 66.3 ° respectively) as a result of the repulsion between the oxygen atoms. The 0(2)...0(3) distance is thus increased to 3.00 and 3.15/i, respectively: a little more than the normal oxygen-oxygen van der Waals separation of 2.8 A.…”

From Aryl Bromides to Enantioenriched Benzylic Alcohols in a Single Flask: Catalytic Asymmetric Arylation of Aldehydes

“…The catalytic asymmetric addition of aryl groups to aldehydes has generated an enormous amount of attention 1. The resulting diarylmethanols are important constituents of biologically active compounds, such as clemastine,2 orphenadrine,3, 4 neobenodine,3, 4 chloropheniramine,5, 6 cizolirtine,7 and carbinoxamine 8. Although the majority of enantioselective aldehyde arylation reactions rely on the use of costly diphenylzinc ($55–75 g −1 ), important advances in the use of other aryl transfer reagents, such as arylboronic acids9, 10 and Ph 2 Si(OMe) 2 ,11 have been reported.…”

Predicting Retention and Separation Factors of Chiral Diarylmethane Derivates by QSPR Models

“…Thederivatespossessingdiarylmethanemoietyoftenexhibit variousbiologicalactivities.Forexample,clemastine((+)-(R,R)-1), 1 neobenodine((+)-(R)-2), 2 andchlorpheniramine((+)-(S)-3) 3 ( Fig.1),wereusedasanticholinergicdrugstotreatanaphylactias, suchasrhinitisandhives,orusedaslocalanaestheticandlaxative agents. 4 Inrecentyears,ithasbeenfoundthatthistypeofcompoundsshowsinhibitoryactivityagainstoestrogensynthetaseand humanimmunodeficiencyvirus(HIV)-1recombinantreverse transcriptase 5,6 aswellasantitubercularactivity 7 .Whentwoaryl groupsdifferfromeachother,themoleculewillpresentchirality andeveryenantiomermaydisplaydifferentbiologicalactivity,e.…”