58416-59-4

Upstream product

• 108-99-6 3-Methylpyridine 
• 100-39-0 benzyl bromide 

Downstream Products

• 40240-24-2 1-benzyl-5-methyl-1,2,3,6-tetrahydropyridine 
• 212008-99-6 1-benzyl-3-methyl-1,2,5,6-tetrahydropyridine N-oxide 
• 162465-70-5 1-benzyl-4-methoxy-3-methyl-1,4,5,6-tetrahydropyridine 
• 212008-89-4 1-Benzyl-3-methyl-1,2,5,6-tetrahydro-pyridine-2-carbonitrile 
• 154471-94-0 1-Benzyl-3-methyl-1,4-dihydro-pyridine 

Relevant academic research and scientific papers

Potent and Selective Tetrahydroisoquinoline Kappa Opioid Receptor Antagonists of Lead Compound (3 R)-7-Hydroxy- N-[(1 S)-2-methyl-1-(piperidin-1-ylmethyl)propyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (PDTic)

Past studies have shown that it has been difficult to discover and develop potent and selective κ opioid receptor antagonists, particularly compounds having potential for clinical development. In this study, we present a structure-activity relationship (SAR) study of a recently discovered new class of tetrahydroisoquinoline κ opioid receptor antagonists which led to (3R)-7-hydroxy-N-{(1S)-2-methyl-1-[(-4-methylpiperidine-1-yl)methyl]propyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (12) (4-Me-PDTic). Compound 12 had a Ke = 0.37 nM in a [35S]GTPγS binding assay and was 645- and >8100-fold selective for the κ relative to the μ and δ opioid receptors, respectively. Calculated log BB and CNS (central nervous system) multiparameter optimization (MPO) and low molecular weight values all predict that 12 will penetrate the brain, and pharmacokinetic studies in rats show that 12 does indeed penetrate the brain.

Asymmetric Hydrogenation of 3-Substituted Pyridinium Salts

The use of an equivalent amount of an organic base leads to high enantiomeric excess in the asymmetric hydrogenation of N-benzylated 3-substituted pyridinium salts into the corresponding piperidines. Indeed, in the presence of Et3N, a Rh-JosiPhos catalyst reduced a range of pyridinium salts with ee values up to 90 %. The role of the base was elucidated with a mechanistic study involving the isolation of the various reaction intermediates and isotopic labeling experiments. Additionally, this study provided some evidence for an enantiodetermining step involving a dihydropyridine intermediate.

Azaquinazoline Inhibitors Of Atypical Protein Kinase C

The present application provides a compound of formula (I) and/or a salt thereof, wherein R1, G, and X are as defined herein. A compound of formula (I) and/or its salts have aPKC inhibitory activity, and may be used to treat proliferative disor

IMIDAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING PHARMACOKINETICS OF DRUG

Imidazole derivatives of formula (I), pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising at least one imidazole derivative are disclosed. The imidazole derivatives are effective to inhibit CYP450 3A and can be used to improve the pharmacokinetics of a drug that is metabolized by CYP450 3A4.

IMIDAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR IMPROVING THE PHARMACOKINETICS OF A DRUG

The present invention relates to Imidazole Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Y, R1 and R2 are as defined herein. The present invention also relates to compositions comprising at least one Imidazole Derivative, and and methods of using the Imidazole Derivatives for inhibiting CYP450 3A. Inhibition of CYP450 3A can be used to improve the pharmacokinetics of a drug that is metabolized by CYP450 3A4.

The role of ion/neutral complexes in the fragmentation of N-benzyl-(alkylpyridinium) ions

N-Benzylpyridinium ions bearing an alkyl group at the pyridine nucleus were studied as potential precursors of gaseous ion/neutral complexes. The occurrence of I/N complexes [C6H5CH2 + ? alkylpyridine] was probed by the reactivity of the potential benzylic hydride donor sites present in the ortho-, meta- and para-alkyl groups (R = methyl, ethyl, isopropyl and benzyl). Collision-induced dissociation of the ions, carried out in an electrical ion cage mass spectrometer, revealed that hydride transfer strongly depends both on the energy requirements of the hydride transfer but also on the position of the hydride donor. Hydride transfer, giving rise to the loss of toluene, was found to occur exclusively with those N-benzylpyridinium ions which bear an isopropyl or a benzyl substituent in the ortho position of the pyridine ring, thus reflecting the intermediacy of I/N complexes. All of the putative hydride donor alkyl groups were found to be non-reactive in the meta and para positions, as were methyl and ethyl groups even in the ortho positions. Density functional calculations (B3LYP/6-311+G/3d,2p)//(B3LYP/6-31+G(d)) on the hydride-transfer and simple-cleavage channels were carried out to help rationalizing these observations. The results suggest that the intra-complex hydride abstraction from the 3- and 4-isopropyl- and from the 3- and 4-benzylpyridine neutrals, although being thermodynamically favorable, is suppressed by substantial intra-complex rotational (or reorientation) barriers.

Stereoselectivity in Diels-Alder reactions of diene-substituted N-alkoxycarbonyl-1,2-dihydropyridines

(Chemical Equation Presented) Diene substituent effects on the regiochemical and stereochemical outcomes of uncatalyzed Diels-Alder reactions of N-alkoxycarbonyl-1,2-dihydropyridines with both styrene and methyl vinyl ketone (MVK) were studied. Alkyl subs

Equilibrium Acidities and Homolytic Bond Dissociation Energies of the Acidic C-H Bonds in N-Substituted Trimethylammonium and Pyridinium Cations

Equilibrium acidities (pKHAs) of the cations in sixteen N-substituted trimethylammonium salts, one N-phenacylquinuclidinium salt, eight N-substituted pyridinium salts, and N-(ethoxycarbonyl)-isoquinolinium bromide, together with the oxidation potentials of their conjugate bases, have been determined in dimethyl sulfoxide (DMSO) solution.The acidifying effects of the α-trimethylammonium groups (α-Me3N+) and the α-pyridinium groups (α-PyN+) on the adjacent acidic C-H bonds in these cations were found to average about 10 and 18 pKHA units, respectively, in DMSO.The homolytic bond dissociation energies of the acidic C-H bonds in these cations, estimated by the combination of the equilibrium acidities with the oxidation potentials of their corresponding conjugate bases (ylides), show that the α-trimethylammonium groups destabilize adjacent radicals by 2-6 kcal/mol, whereas α-pyridinium groups stabilize adjacent radicals by 3-6 kcal/mol.The effects of α-pyridinium groups on the stabilization energies of the radicals derived from these cations were found to be ca. 4-10 kcal/mol smaller than those of the corresponding phenyl groups, whereas their effects on the equilibrium acidities of the cations were 5.4-13.1 pKHA units larger.The pKHA value of tetramethylammonium cation (Me4N+) was estimated by extrapolation to be about 42 in DMSO.

MUTUAL EFFECTS OF THE STRUCTURE IN THE REACTIONS OF BENZYL BROMIDES WITH PYRIDINES

The rate of the reactions of benzyl bromides with pyridines in nitrobenzene at 40 deg C was measured.The nonadditivity of the joint action of the electronic effects of substituents in the molecules of the reagents on the reactivity of the benzyl bromide-p