36938-77-9

Upstream product

• 14548-48-2 4-(4-chlorobenzoyl)pyridine 
• 141-52-6 sodium ethanolate 
• 100-48-1 pyridine-4-carbonitrile 
• 39030-46-1 2-((4-chlorobenzyl)oxy)isoindoline-1,3-dione 
• 104-88-1 4-chlorobenzaldehyde 

Downstream Products

• 358971-58-1 (pyridin-4-yl)-(4-chlorophenyl)chloromethane 
• 36938-75-7 (4-chlorophenyl)(piperidin-4-yl)methanol 
• 359402-81-6 (4-pyridyl)-(4-chlorophenyl)bromomethane 
• 38077-13-3 4-(p-Chloro-α-hydroxybenzyl)-1-[3-(p-fluorobenzoyl)propyl]piperidine 
• 125742-50-9 1-[4-chlorophenyl(pyridin-4-yl)methyl]piperazine 

Relevant academic research and scientific papers

Benzylic C-H heteroarylation of: N-(benzyloxy)phthalimides with cyanopyridines enabled by photoredox 1,2-hydrogen atom transfer

A visible light initiated α-C(sp3)-H arylation of N-(benzyloxy)phthalimides with cyanopyridines for the construction of highly valuable pyridinyl-containing diarylmethanols, including bioactive motif-based analogues, is reported. This method enables arylation of the C(sp3)-H bonds adjacent to an oxygen atom through alkoxy radical formation by O-N bond cleavage, 1,2-hydrogen atom transfer (HAT), arylation and C-CN bond cleavage cascades, and offers a means to exploit 1,2-HAT modes to incorporate functional groups for constructing functionalized alcohols.

Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study

Density functional theory investigations revealed that the pyridine-boryl radical generated in situ using 4-cyanopyridine and bis(pinacolato)diboron could be used as a bifunctional “reagent”, which serves as not only a pyridine precursor but also a boryl radical. With the unique reactivity of such radicals, 4-substituted pyridine derivatives could be synthesized using α,β-unsaturated ketones and 4-cyanopyridine via a novel radical addition/C-C coupling mechanism. Several controlled experiments were conducted to provide supportive evidence for the proposed mechanism. In addition to enones, the scope could be extended to a wide range of boryl radical acceptors, including various aldehydes and ketones, aryl imines and alkynones. Lastly, this transformation was applied in the late-stage modification of a complicated pharmaceutical molecule.

Design, Synthesis, and Evaluation of Metabolism-Based Analogues of Haloperidol Incapable of Forming MPP+-like Species

The long-term, irreversible, Parkinsonism-like side effects of haloperidol have been speculated to involve several mechanisms. More recently, it has been speculated that the metabolic transformation to MPP+-like species may contribute to the Parkinsonism-like side effects. Because BCPP+ and its reduced analogue have been shown to possess the potential to destroy dopamine receptors in the nigrostriatum, we have designed new analogues of haloperidol lacking the structural features necessary to form neurotoxic quaternary species but retaining their dopamine-binding capacity. The most potent agent at the D2 receptor, the homopiperidine analogue 11, was found to be equipotent to haloperidol. It was also of interest to identify analogues with DA binding profiles similar to that of clozapine at the dopamine receptor subtypes. Evaluation of the proposed agents shows that the ratio of D2 to D4 (2) binding of clozapine was mimicked by 7 [Ki(D2) = 33, Ki(D3) = 200, Ki(D4) = 11 nM; Ki(D2)/Ki(D4) = 3] and 9 [Ki(D2) = 44, Ki(D3) = 170, Ki(D4) = 24 nM; Ki(D2)/Ki(D4) = 2]. A preliminary in-vivo testing of compound 7 shows that its behavioral profile is similar to that of clozapine. This profile suggests that there is a need for further evaluation of these two synthetic agents and their enantiomers for efficacy and lack of catalepsy in animal models.

Pharmaceutical compositions containing azetidine derivatives, novel azetidine derivatives and their preparation

The present invention relates to pharmaceutical compositions containing, as an active ingredient, at least one compound of formula: in which R1represents a radical —N(R4)R5, —N(R4)—CO—R5, —N(R4)—SO2R6or one of its pharmaceutically acceptable salts, to the novel derivatives of formula (I), to their pharmaceutically acceptable salts and to their preparation.

Azetidine derivatives, their preparation and pharmaceutical compositions containing them

Compounds of formula: in which R represents a CR1R2, C═C(R5)SO2R6 or C═C(R7)SO2alk radical, their preparation and the pharmaceutical compositions containing them.

Inhibitors of farnesyl protein transferase. 4-Amido, 4-carbamoyl, and 4- carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine

The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4- carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H- benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine to explore the SAR of of this series of FPT inhibitors is described. This resulted in the synthesis of the 4-and 3-pyridylacetyl analogues 45a and 50a, respectively, both of which were orally active but were found to be rapidly metabolized in vivo. Identification of the principal metabolites led to the synthesis of a variety of new compounds that would be less readily metabolized, the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and 83a. Novel replacements for the pyridylacetyl moiety were also sought, and this resulted in the discovery of the 4-N-methyl and 4-N-carboxamidopiperidinylacetyl derivatives 135a and 160a, respectively. All of these derivatives exhibited greatly improved pharmacokinetics. The synthesis of the corresponding 3- bromo analogues resulted in the discovery of the 4-pyridylacetyl N-oxides 83b (±) and 85b [11S(-)] and the 4-carboxamidopiperidinylacetamido derivative 160b (±), all of which exhibited potent FPT inhibition in vitro. All three showed excellent oral bioavailability in vivo in nude mice and cynomolgus monkeys and exhibited excellent antitumor efficacy against a series of tumor cell lines when dosed orally in nude mice.