333986-31-5

Upstream product

• 241138-40-9 1-(methylsulfonyl)piperidine-4-carbonyl chloride 
• 280772-00-1 1-(Methylsulfonyl)-4-piperidine Carboxylic Acid 
• 79-37-8 oxalyl dichloride 
• 95-76-1 m,p-dichloroaniline 
• 5470-15-5 N-(3,4-dichlorophenyl)formamide 
• 1126-09-6 4-carbethoxypiperidine 
• 333986-28-0 N-(3-chloropropyl)-N-(3,4-dichlorophenyl)formamide 
• 217487-18-8 1-methanesulfonylpiperidine-4-carboxylic acid ethyl ester 

Downstream Products

• 333992-35-1 4-(1-{3-[(3,4-dichloro-phenyl)-(1-methanesulfonyl-piperidine-4-carbonyl)-amino]-propyl}-piperidin-4-ylmethyl)-benzoic acid methyl ester 
• 333994-97-1 N-(3,4-Dichlorophenyl)-N-{3-[4-(4-{[(2-hydroxyethyl)amino]carbonyl}benzyl)-1-piperidinyl]propyl}-1-(methylsulfonyl)-4-piperidinecarboxamide Hydrochloride 
• 333993-78-5 N-(3,4-Dichlorophenyl)-1-(methylsulfonyl)-N-[3-(4-{4-[(propylamino)sulfonyl]benzyl}-1-piperidinyl)propyl]4-piperidinecarboxamide 
• 333993-36-5 N-{3-[4-(4-aminobenzyl)-1-piperidinyl]propyl}-N-(3,4-dichlorophenyl)-1-(methylsulfonyl)-4-piperidinecarboxamide 
• 333991-95-0 N-(3-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}propyl)-N-(3,4-dichlorophenyl)-1-(methylsulfonyl)piperidine-4-carboxamide 

Relevant academic research and scientific papers

Discovery of a piperidine-4-carboxamide CCR5 antagonist (TAK-220) with highly potent anti-HIV-1 activity

We incorporated various polar groups into previously described piperidine-4-carboxamide CCR5 antagonists to improve their metabolic stability in human hepatic microsomes. Introducing a carbamoyl group into the phenyl ring of the 4-benzylpiperidine moiety

CCR5 antagonists as anti-HIV-1 agents. Part 3: Synthesis and biological evaluation of piperidine-4-carboxamide derivatives

Replacement of the 5-oxopyrrolidin-3-yl fragment in the previously reported lead structure with a 1-acetylpiperidin-4-yl group led to the discovery of a novel series of potent CCR5 antagonists. Introduction of small hydrophobic substituents on the central phenyl ring increased the binding affinity, providing low to sub-nanomolar CCR5 antagonists. The selected compound 11f showed excellent antiviral activity against CCR5-using HIV-1 replication in human peripheral blood mononuclear cells (EC50 = 0.59 nM) and an acceptable pharmacokinetic profile in dogs.

Cyclic amine compounds as CCR5 antagonists

A compound of formula (I) (wherein R1is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R2is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R1and R2may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N+—R5.Y?(R5is a hydrocarbon group; Y?is a counter anion); R3is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R4is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group(s) other than oxo; G1is a bond, CO or SO2; G2is CO, SO2, NHCO, CONH or OCO; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C1-3aliphatic hydrocarbon which may be substituted; provided that J is methine when G2is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group(s) when G1is a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in human (e.g. AIDS).

PROCESS FOR PREPARATION OF BENZYLPIPERIDINE COMPOUNDS

According to the process as shown in the following scheme having a step for reacting Compound (I) with Compound (II) to produce Compound (III), benzylpiperidine compounds useful as synthesis starting materials of pharmaceutical agents, agricultural chemicals and the like can be produced conveniently by a short step: wherein R1 is a hydrogen atom or an amino-protecting group, R2 is a hydrogen atom, a hydrocarbon group optionally having substituents, an alkoxy group optionally having substituents or a heterocyclic group optionally having substituents, and R3 is a lower alkyl group.