The Crystal and Molecular Structure of the Antihistaminic Drug Triprolidine Hydrochloride Monohydrate [<i>trans</i>-1-(<i>p</i>-Tolyl)-1-(2-pyridyl)-3-(1-pyrrolidino)-prop-1-ene]

James, Michael N.G.; Williams, G. J. B.

doi:10.1139/v74-268

Cited by 14 publications

(2 citation statements)

References 9 publications

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“…In two previous papers (Bertolasi, Borea, Gilli & Sacerdoti, 1980a, b) we have reported the crystal and molecular structures of two histamine Hi receptor antagonists, carbinoxamine maleate and cyclizine hydrochloride, and have shown that their conformations in the crystal correspond reasonably well to those calculated by minimizing the non-bonded intramolecular potential energy. The preferred conformation of antihistamines assumes particular importance in consequence of the high degree of conformational freedom of these molecules and in view of the hypothesis (Witiak, Muhi-Eldeen, Mahishi, Sethi & Gerald, 1971;James & Williams, 1974) that a fixed distance between the amino nitrogen and the centroid of an unsaturated ring is determinant for antihistaminic activity.…”

Section: Mean Of Six Experiments Each)mentioning

confidence: 99%

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

1981

British J Pharmacology

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Some CCK-like peptides were tested for their effects on gastric emptying in the rat, taking into account their spasmogenic action on the gastroduodenal junction observed in previous papers (Bertaccini, Impicciatore & De Caro, 1973; Bertaccini, Impicciatore, De Caro, Chiavarini & Burani, 1974). Gastric emptying of a phenol red meal was evaluated by a modification (Scarpignato and Bertaccini, 1980) of the method described by Reynell & Spray (1956). Male rats weighing 200 g were used after a fasting period of 24 h. Peptides used were: caerulein, C-terminal heptapeptide of CCK (hepta-CCK) and pentagastrin. They were injected i.p. in a constant volume of 1 ml/kg 5 min prior to administration of the meal. Rats were killed at various time intervals to evaluate the duration of the effect. A fixed time (20 min) was selected for the study of the dose-response relationship. All the peptides delayed gastric emptying in a dosedependent fashion: threshold doses were 0.075 .g/kg for caerulein and hepta-CCK. Both peptides caused a complete block of gastric emptying with doses of 5 gg/kg. Pentagastrin had a threshold dose at 10 pg/kg; the maximum dose (80 pg/kg) caused an 104P PROCEEDINGS OF THE B.P.S., 30th JUNE, 1st JULY, 1980 Table I 'Characteristics' of emptying patterns Calculated Half-life emptying time Treatment (min) (min) Controls 15.3 + 6.2' 120.9 + 6.1 Caerulein (1 bg/kg) 49.0 + 14.32 220.6 + 14.32 Hepta-CCK (1 p.g/kg) 53.3 + 14.32 289.3 + 14.22 Pentagastrin (80 bg/kg) 23.8 + 7.73 146.0 + 7.73 1 Mean value + 95W confidence limits. 2 Statistically significant difference (P < 0.001) in comparison with control values. Statistically significant difference (P < 0.01) in comparison with control values. suggest that the delay in gastric emptying induced by CCK-like peptides is connected with the contraction of the pylorus pointed out in previous studies. Therefore the pyloric sphincter appears to play an important role in the regulation of emptying of liquids in rats, unlike cats and dogs (Stemper & Cooke, 1976) in which gastric emptying of liquids was shown to be independent of the gastroduodenal junction.

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Section: Mean Of Six Experiments Each)mentioning

confidence: 99%

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

1981

British J Pharmacology

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“…Ring I Ring n Ring I Ring n ~x4 x2~xl Me bridge Structural Database [13,14], while phenindamine was built with the modeling package Chem-X* using crystal structure fragments.…”

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The histamine H1-receptor antagonist binding site. Part I: Active conformation of cyproheptadine

Drooge

Kelder

Timmerman

1991

J Computer-Aided Mol Des

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The active conformation of several histamine H1-antagonists is investigated. As a template molecule we used the antagonist cyproheptadine, which consists of a piperidylene ring connected to a tricyclic system. The piperidylene moiety is shown to be flexible. The global minimum is a chair conformation but, additionally, a second chair and various boat conformations have to be considered, as their energies are less than 5 kcal/mol above the energy of the global minimum. Two semi-rigid histamine H1-antagonists, phenindamine and triprolidine, were fitted onto the various conformations of cyproheptadine in order to derive the pharmacologically active conformation of cyproheptadine. At the same time, the active conformation of both phenindamine and triprolidine was derived. It is demonstrated that, within the receptor-bound conformation of cyproheptadine, the piperidylene ring most probably exists in a boat form.

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Differential protonation and dynamic structure of doxylamine succinate in solution using ¹H and ¹³C NMR

Somashekar¹,

Gowda²,

Ramesha³

et al. 2004

Magnetic Reson in Chemistry

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A protonation and dynamic structural study of doxylamine succinate, a 1:1 salt of succinic acid with dimethyl-[2-(1-phenyl-1-pyridin-2-yl-ethoxy)ethyl]amine, in solution using one- and two-dimensional 1H and 13C NMR experiments at variable temperature and concentration is presented. The two acidic protons of the salt doxylamine succinate are in 'intermediate' exchange at room temperature, as evidenced by the appearance of a broad signal. This signal evolves into two distinct signals below about -30 degrees C. A two-dimensional 1H-1H double quantum filtered correlation experiment carried out at -55 degrees C shows protonation of one of the acidic protons to the dimethylamine nitrogen. A two-dimensional rotating frame 1H-1H NOE experiment at the same temperature reveals that the other proton remains with the succinate moiety. Comparison of the 1H and 13C chemical shifts and the 13C T1 relaxation times of the salt with those of the free base further substantiate the findings.

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The Crystal and Molecular Structure of the Antihistaminic Drug Triprolidine Hydrochloride Monohydrate [trans-1-(p-Tolyl)-1-(2-pyridyl)-3-(1-pyrrolidino)-prop-1-ene]

Abstract: T h e title compound crystallizes from anisole with 4 molecules per unit cell. T h e space group o f this cell isCan.

Cited by 14 publications

References 9 publications

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

The histamine H1-receptor antagonist binding site. Part I: Active conformation of cyproheptadine

Differential protonation and dynamic structure of doxylamine succinate in solution using ¹H and ¹³C NMR

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The Crystal and Molecular Structure of the Antihistaminic Drug Triprolidine Hydrochloride Monohydrate [trans-1-(p-Tolyl)-1-(2-pyridyl)-3-(1-pyrrolidino)-prop-1-ene]

Abstract: T h e title compound crystallizes from anisole with 4 molecules per unit cell. T h e space group o f this cell isCan.

Cited by 14 publications

References 9 publications

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

The histamine H1-receptor antagonist binding site. Part I: Active conformation of cyproheptadine

Differential protonation and dynamic structure of doxylamine succinate in solution using 1H and 13C NMR

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Differential protonation and dynamic structure of doxylamine succinate in solution using ¹H and ¹³C NMR