Search results for "DISCOVERY"
showing 10 items of 4119 documents
Triazolopyridines. Part 8.1 Nucleophilic substitution reactions of 5-bromo[1,2,3]triazolo[5,1-a]isoquinoline and 7-bromo[1,2,3]-triazolo[1,5-a]pyridi…
1988
Abstract Nucleophilic substitution of 5-bromotriazoloisoquinoline (3) and of 7-bromo-3-methyltriazolopyridine (6) proceeds readily to give a range of 5-substituted triazoloisoquinolines (4a)-(4e), and of 7-substituted triazolopyridines (7a)-(7h) respectively. Triazoloisoquinolines have been converted into 1,3-disubstituted isoquinolines (11)-(13), (15), and (16), and triazolopyridines into 2,6-disubstituted pyridines (17)-(19). Of secondary amine nucleophiles, only piperidine reacted with 7-bromo-3-methyltriazolopyridine (6) to give the 7-substituted derivative (7g). A second product in this reaction was a 2,6-disubstituted pyridine (8); the similar compounds (20)-(24) were the only product…
Nucleophilic substitutions on bromotriazolopyridines - an improved route to 2,6-disubstituted pyridines and to 1,3-disubstituted isoquinolines
1986
Abstract A regiospecific synthesis of 2,6-disubstituted pyridines and of 1,3-disubstituted isoquinolines is described.
Photochemistry of 7-acetoxybenzopyran derivatives. Synthesis of eupatoriochromene and encecalin
1989
Abstract The photolysis of the 7-acetoxybenzopyran derivatives 1a-5a has been carried out. Chromene 1a was found to undergo extensive photopolymerization. Chromanone 2a underwent a rather inefficient photo-Fries rearrangement to the 6 - and 8 - acetyl derivatives 2b and 2c . Diacetoxychromene 3a gave the unsaturated ketone 8 as the main product, besides its deacetylation analogue 9 and chromanone 11 . Diacetoxychroman 4a afforded a mixture of four C-acetyl products: 1b, 1c, 2b and 2c , together with Chromene 1a and chromanone 2a. Finally, irradiation of chroman 5a gave rise to a mixture of the two possible photo-Fries products 5b (43%) and 5c (52%). The mechanistic implications of the above…
Ring transformation of furfural into an unusual bicyclic system: Characterisation and dynamic stereochemistry of 6,7-diethoxycarbonyl-6,7-diaza-8-oxa…
1997
Abstract 2-Formylthiophene and 3-formylindole react with diethyl azodicarboxylate to give simple products derived from reactions on the formyl group whereas 2-formylfuran reacts to give the unexpected bicyclic title compound. 1 H and 13 C NMR studies indicate that this compound undergoes a series of three dynamic conformational changes over the temperature range 50 to −90°C which are ascribed to slow rotation about the exocyclic carbamate bonds and hindered bridge inversion.
Auxiliary-controlled stereoselective enolate protonation: Enantioselective synthesis of cis and trans annulated decahydroquinoline alkaloids
1998
Abstract The diastereoselective synthesis of the octahydroquinoline enone precursor of pumiliotoxin C is achieved via tandem Mannich-Michael reaction on N-galactosyl imines. Conjugate cuprate addition to the bicyclic enone stereoselectively forms the trans annulated 4a- epi -pumiliotoxin C skeleton in the presence of the carbohydrate auxiliary, and the cis annulated pumiliotoxin C skeleton in its absence.
Preparation of dopaminergic N-alkyl-benzyltetrahydroisoquinolines using a 'one-pot' procedure in acid medium.
2000
The preparation of N-methyl-BTHIQ (4) from N-phenylethyl-phenacetamide (1) by cyclization, reduction and N-alkylation in acid medium has been achieved in good yield in a 'one-pot' procedure. Acylation of imine (2) intermediate afforded the Z and E stereoselectivity in the enamide formation. 6-Hydroxy-BTHIQ (7) shows selectivity for D2 dopamine receptors, while its N-methylated homologue (8) displays higher affinities for both D1 and D2 receptor types, with an unexpected increase in D1 dopamine receptor affinity.
Two-carbon bridge substituted cocaines: enantioselective synthesis, attribution of the absolute configuration and biological activity of novel 6- and…
1999
In an effort to learn more about the general structure-activity relationships of cocaine with the aim to elucidate those structural features that might confer antagonistic properties to such analogues, we describe herein our synthetic efforts to prepare two-carbon bridge functionalized (methoxylated and hydroxylated) analogues. Our approach makes use of a modification of the classical Willstatter synthesis of cocaine: Mannich type cyclization of acetonedicarboxylic acid monomethyl ester with methylamine hydrochloride and 2-methoxysuccindialdehyde in a citrate buffer solution afforded the 6- and 7-substituted 2-carbomethoxy-3-tropinones 3a,b and 4a,b in approximate yields of 64%. Reduction o…
A Practical Perspective: The Effect of Ligand Conformers on the Negative Image-Based Screening.
2019
Negative image-based (NIB) screening is a rigid molecular docking methodology that can also be employed in docking rescoring. During the NIB screening, a negative image is generated based on the target protein’s ligand-binding cavity by inverting its shape and electrostatics. The resulting NIB model is a drug-like entity or pseudo-ligand that is compared directly against ligand 3D conformers, as is done with a template compound in the ligand-based screening. This cavity-based rigid docking has been demonstrated to work with genuine drug targets in both benchmark testing and drug candidate/lead discovery. Firstly, the study explores in-depth the applicability of different ligand 3D conformer…
Application of a low transition temperature mixture for the dispersive liquid–liquid microextraction of illicit drugs from urine samples
2021
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