10338-69-9

Basic information

• Product Name: 1,2,3,6-Tetrahydro-4-phenyl-pyridine
• Synonyms: 4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE;1,2,3,6-tetrahydro-4-phenyl-pyridine;4-Phenyl-1,2,3,6-tetrahydropyr;Pyridine, 1,2,3,6-tetrahydro-4-phenyl-;1,2,3,6-tetrahydro-4-phenyl-pyridine:4-phenyl-1,2,3,6-tetrahydropyridine
• CAS NO: 10338-69-9
• Molecular Formula: C₁₁H₁₃N
• Molecular Weight: 159.23
• EINECS: 256-071-5
• Product Categories: Pyridines derivates
• Mol File: 10338-69-9.mol

Chemical Properties

• Boiling Point: 267.923 °C at 760 mmHg
• Flash Point: 119.944 °C
• Appearance: /
• Density: 1.008 g/cm³
• Storage Temp.: 2-8°C(protect from light)
• PKA: 9.41±0.10(Predicted)
• CAS DataBase Reference: 1,2,3,6-Tetrahydro-4-phenyl-pyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 1,2,3,6-Tetrahydro-4-phenyl-pyridine(10338-69-9)
• EPA Substance Registry System: 1,2,3,6-Tetrahydro-4-phenyl-pyridine(10338-69-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36-51
• Safety Statements: 26
• Hazardous Substances Data: 10338-69-9(Hazardous Substances Data)

Usage

Synthesis Reference(s)

Journal of the American Chemical Society, 78, p. 1702, 1956 DOI: 10.1021/ja01589a060

InChI:InChI=1/C11H13N.ClH/c1-2-4-10(5-3-1)11-6-8-12-9-7-11;/h1-6,12H,7-9H2;1H

Upstream product

• 19798-94-8 6-methyl-6-phenyl-[1,3]oxazinane 
• 137-40-6 sodium proprionate 
• 80866-85-9 4-bromo-4-phenyl-piperidine; hydrobromide 
• 802294-64-0 propionic acid 
• 98-83-9 isopropenylbenzene 
• 50-00-0 formaldehyd 
• 28289-54-5 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine 
• 7647-01-0 hydrogenchloride 
• 98-80-6 phenylboronic acid 
• 40807-61-2 4-hydroxy-4-phenylpiperidin 
• 108-86-1 bromobenzene 
• 939-23-1 p-phenylpyridine 
• 591-51-5 phenyllithium 
• 43064-12-6 1,2,3,6-tetrahydro-4-phenylpyridine hydrochloride 

Downstream Products

• 939-23-1 p-phenylpyridine 
• 771-99-3 4-phenylpiperidine 
• 80866-85-9 4-bromo-4-phenyl-piperidine; hydrobromide 
• 32273-45-3 1-(cyanomethyl)-4-phenyl-1,2,3,6-tetrahydropyridine 
• 109241-03-4 1-(2'-iodobenzoyl)-4-phenyl-1,2,5,6-tetrahydropyridine 
• 127331-73-1 1-Phenoxy-4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-butan-2-ol 
• 123333-02-8 N-<(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)methylene>-1,1-dimethylethanamine 
• 4600-95-7 1-ethoxycarbonyl-4-phenyl-1,2,5,6-tetrahydropyridine 
• 105277-32-5 7-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propoxy]-4H-1-benzopyran-4-one 
• 127625-39-2 2-<2-(4-phenyl-1,2,3,6-tetrahydropyridyl)ethyl>-2H-naphth<1,8-cd>isothiazole 1,1-dioxide 
• 127625-30-3 2-<3-(4-phenyl-1,2,3,6-tetrahydropyridyl)propyl>-2H-naphth<1,8-cd>isothiazole 1,1-dioxide 
• 127625-43-8 2-<4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl>-2H-naphth<1,8-cd>isothiazole 1,1-dioxide 

Relevant articles and documents

Cytochrome P4502D and -2C enzymes catalyze the oxidative N-demethylation of the Parkinsonism-inducing substance 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in rat liver microsomes

We have examined the oxidative N-demethylation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a Parkinsonism-inducing neurotoxin, in liver microsomes from adult Wistar and Dark Agouti (DA) rats. The oxidation of MPTP to 4-phenyl-1,2,3,6-tetrahydropyridine (PTP) in these preparations required NADPH as a cofactor and was significantly inhibited by SKF 525-A (2 mM). MPTP N-demethylation exhibited biphasic kinetics, consistent with two enzymes, a low Km system (Km1, 10.0 ± 2.2 μM; Vmax1, 0.048 ± 0.009 nmol/(min·mg of protein)) and a high Km system (Km2, 1180 ± 91 μM; Vmax2, 4.80 ± 0.75 nmol/(min·mg of protein)). We thus employed two substrate concentrations, 5 μM and 5 mM, for the low and high Km system, respectively, to assay enzyme activity in subsequent experiments. The oxidation activity was significantly decreased by pretreatment of rats with phenobarbital and β-naphthoflavone. Furthermore, marked strain (Wistar > DA) and sex (male > female) differences were observed at low (5 μM) and high (5 mM) substrate concentrations, respectively. Reconstitution experiments with cytochrome P450BTL, which belongs to the P4502D subfamily, and P450ml (P4502C11) demonstrated that MPTP N-demethylase occurs at concentrations of 5 μM and 5 mM. At 5 mM the male-specific P450ml showed a remarkably high activity, over 400-fold that of P450BTL. Polyclonal antibodies against P450BTL and P450ml effectively suppressed the activity at the low (5 μM) and the high (5 mM) substrate concentrations, respectively. These results suggest that, in the microsomal preparations used, MPTP N-demethylation is mainly mediated by P4502D enzyme(s) at lower substrate concentrations and by P4502C11 at higher substrate concentrations.

Rat liver microsomal enzyme catalyzed oxidation of 4-phenyl-trans-1-(2-phenylcyclopropyl)-1,2,3,6-tetrahydropyridine

As part of our ongoing studies to characterize the catalytic pathway(s) for the monoamide oxidase and cytochrome P450 catalyzed oxidations of 1,4-disubstituted 1,2,3,6-tetrahydropyridinyl derivatives, we have examined the metabolic fate of 4-phenyl-trans-1-(2-phenylcyclopropyl)-1,2,3,6-tetrahydropyiridine in NADPH supplemented rat liver microsomes. Three metabolic pathways have been identified: (1) allylic ring α-carbon oxidation to yield the dihydropyridinium species, (2) nitrogen oxidation to yield the N-oxide and (3) N-dealkylation to yield 4-phenyl-1,2,3,6-tetrahydropyridine and cinnamaldehyde. A possible mechanism to account for the formation of cinnamaldehyde involves an initial single electron transfer from the nitrogen lone pair to the iron oxo system Fe+3(O) to form the corresponding cyclopropylaminyl radical cation that will be processed further to the final products. The reaction pathway leading to the dihydropyridinium metabolite may also proceed via the same radical cation intermediate but direct experimental evidence to this effect remains to be obtained. Copyright

B(C6F5)3-Catalyzed Cascade Reduction of Pyridines

B(C6F5)3 has been found to be an effective catalyst for reduction of pyridines and other electron-deficient N-heteroarenes with hydrosilanes (or hydroboranes) and amines as the reducing reagents. The success of this development hinges upon the realization of a cascade process of dearomative hydrosilylation (or hydroboration) and transfer hydrogenation. The broad functional-group tolerance (e.g. ketone, ester, unactivated olefins, nitro, nitrile, heterocycles, etc.) implies high practical utility.

The use of organolithium reagents for the synthesis of 4-aryl-2-phenylpyridines and their corresponding iridium(III) complexes

A versatile palladium-free route for the synthesis of 4-aryl-substituted phenylpyridines (ppy), starting from tert-butyl 4-oxopiperidine-1-carboxylate, is reported. Reaction with an aryllithium, followed by trifluoroacetic acid dehydration/deprotection and oxidation with 2-iodoylbenzoic acid and finally phenylation, gave 4 ligands (L1-4H): 2,4-diphenylpyridine, 4-(4-methoxyphenyl)-2-phenylpyridine, 2-phenyl-4-(o-tolyl)pyridine and 4-mesityl-2-phenylpyridine. These ligands were coordinated to iridium to give the corresponding Ir(L)2(A) complexes (Ir1-7), where A = ancillary ligand acetylacetate or 2-picolinate. This was used to demonstrate that, through a combination of ancillary ligand choice and torsional twisting between the 4-aryl substituents of the ppy ligands, it is possible to tune the phosphorescent emission of the complexes in the range 502-560 nm.

Synthesis and biological evaluation of 1-(isoxazol-5-ylmethylaminoethyl)-4- phenyl tetrahydropyridine and piperidine derivatives as potent T-type calcium channel blockers with antinociceptive effect in a neuropathic pain model

New tetrahydropyridinyl and piperidinyl ethylamine derivatives were designed with hypothetical mapping on pharmacophore model generated from ligand-based virtual screening. The designed compounds were synthesized, and their inhibitory activities on T-type calcium channel were assayed using FDSS and patch-clamp assay. Among them, compounds 7b and 10b showed potent T-type calcium current blocking activity against Cav3.1 (α 1G) and Cav3.2 (α1H) channel simultaneously. With hERG and pharmacokinetics studies, compounds 7b and 10b were evaluated for the antinociceptive effect on rat model of neuropathic pain. They were significantly effective in decreasing the pain responses to mechanical and cold allodynia induced by spinal nerve ligation. These results suggest that modulation of α1G and α1H subtype T-type calcium channels may provide a promising approach for the treatment of neuropathic pain.

Structure-activity relationship exploration of Kv1.3 blockers based on diphenoxylate

Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential therapeutic targets for a range of autoimmune diseases. The molecular basis for this Kv1.3 blockade was assessed by the selective removal of functional groups from the structure of diphenoxylate as well as a number of other structural variations. Removal of the nitrile functional group and replacement of the C-4 piperidinyl substituents resulted in several compounds with submicromolar IC50 values.

Design, synthesis, and evaluation of novel aryl-tetrahydropyridine PPARα/γ dual agonists

Aryl-tetrahydropyridine derivatives were prepared and their PPARα/γ dual agonistic activities were evaluated. Among them, compound (S)-5b was identified as a potent PPARα/γ dual agonist with an EC50 of 1.73 and 0.64 μM in hPPARα and γ, respectively. In diabetic (db/db) mice, compound (S)-5b showed good glucose lowering efficacy and favorable pharmacokinetic properties.

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