333985-70-9

Basic information

• Product Name: 4-Piperidinecarboxamide, 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)-
• CAS NO: 333985-70-9
• Molecular Formula: C18H24Cl2N2O2
• Molecular Weight: 371.307
• Mol File: 333985-70-9.mol

Chemical Properties

• CAS DataBase Reference: 4-Piperidinecarboxamide, 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)-(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Piperidinecarboxamide, 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)-(333985-70-9)
• EPA Substance Registry System: 4-Piperidinecarboxamide, 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)-(333985-70-9)

Safety Data

• Hazardous Substances Data: 333985-70-9(Hazardous Substances Data)

Upstream product

• 59084-16-1 1-acetylpiperidine-4-carbonyl chloride 
• 333985-68-5 (3-chloro-4-methyl-phenyl)-(3-chloro-propyl)-amine 
• 109-70-6 1.3-chlorobromopropane 
• 25503-90-6 1-acetyl-piperidine-4-carboxylic acid 
• 6312-80-7 N-(3-chloro-4-methylphenyl)formamide 
• 888729-78-0 N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)formamide 

Downstream Products

• 333994-00-6 1-acetyl-N-(3-{4-[4-(aminocarbonyl)benzyl]-1-piperidinyl}propyl)-N-(3-chloro-4-methylphenyl)-4-piperidinecarboxamide 
• 872002-10-3 C₂₆H₃₉ClN₄O₂ 
• 1221446-18-9 1-acetyl-N-(3-(3-exo-amino-8-azabicyclo[3.2.1]oct-8-yl)propyl)-N-(3-chloro-4-methylphenyl)-4-piperidinylcarboxamide 
• 1221445-74-4 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-(3-exo-(2-phenylacetamido)-8-azabicyclo[3.2.1]oct-8-yl)propyl)-4-piperidinylcarboxamide 
• 1221446-00-9 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-(3-exo-benzyloxymethanamido-8-azabicyclo[3.2.1]oct-8-yl)propyl)-4-piperidinylcarboxamide 
• 1221446-01-0 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-(3-exo-(methylsulfonylamido)-8-azabicyclo[3.2.1]oct-8-yl)propyl)-4-piperidinylcarboxamide 
• 1221446-07-6 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-(3-exo-(3-(4-methoxylphenyl)ureylene)-8-azabicyclo[3.2.1]oct-8-yl)propyl)-4-piperidinylcarboxamide 
• 1221446-17-8 tert-butyl 8-(3-(1-acetyl-N-(3-chloro-4-methylphenyl)-4-piperidineformamide)propyl)-3-exo-8-azabicyclo[3.2.1]octan-3-carbamate 
• 1221569-04-5 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-(3-exo-(3-isopropyl-5-methyl-4-hydro-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl)propyl)-4-piperidinylcarboxamide 

Relevant articles and documents

A "two-Birds-One-Stone" Approach toward the Design of Bifunctional Human Immunodeficiency Virus Type 1 Entry Inhibitors Targeting the CCR5 Coreceptor and gp41 N-Terminal Heptad Repeat Region

Previous studies have reported the stepwise nature of human immunodeficiency virus type 1 (HIV-1) entry and the pivotal role of coreceptor CCR5 and the gp41 N-terminal heptad repeat (NHR) region in this event. With this in mind, we herein report a dual-targeted drug compound featuring bifunctional entry inhibitors, consisting of a piperidine-4-carboxamide-based CCR5 antagonist, TAK-220, and a gp41 NHR-targeting fusion-inhibitory peptide, C34. The resultant chimeras were constructed by linking both pharmacophores with a polyethylene glycol spacer. One chimera, CP12TAK, exhibited exceptionally potent antiviral activity, about 40- and 306-fold over that of its parent inhibitors, C34 and TAK-220, respectively. In addition to R5-tropic viruses, CP12TAK also strongly inhibited infection of X4-tropic HIV-1 strains. These data are promising for the further development of CP12TAK as a new anti-HIV-1 drug. Results show that this strategy could be extended to the design of therapies against infection of other enveloped viruses.

Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface

To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of the HIV-1 envelope (Env) gp120 protein and the host-cell coreceptor (CoR) protein can be covalently joined into bifunctional synergistic combinations with improved antiviral capabilities. A synthetic protocol was established to covalently combine a CCR5 small-molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components and, at the same time, exhibited low to subnanomolar potencies in inhibiting cell infection by different pseudoviruses, which were substantially greater than those of a noncovalent mixture of the individual components. The results demonstrate that targeting the virus-cell interface with a single molecule can result in improved potencies and also the introduction of new phenotypes to the chimeric inhibitor, such as the irreversible inactivation of HIV-1.

Aminopropyl-substituted tropane amine compound and its pharmaceutical composition, preparation method and use

The invention belongs to the field of pharmaceutical chemistry and discloses a 8-(3-aminopropyl)-3-exo-8-azabicyclo[3. 2. 1]octane-3-amino-amide compound and its pharmaceutical composition and use. The compound or pharmacologically acceptable salt can be

Design, synthesis, and biological evaluation of novel 2-methylpiperazine derivatives as potent CCR5 antagonists

Three series of novel 2-methylpiperazine derivatives were designed and synthesized using a fragment-assembly strategy. Among them, six compounds (13, 16, 18, 22, 33, and 36) showed potent activity against CCR5 comparable to that of the positive control, maraviroc, in calcium mobilization assay. Moreover, some compounds were selected and further tested for their antiviral activity in HIV-1 single cycle assay. As a result, four compounds (13, 16, 33, and 36) showed antiviral activity at the nanomolar level. Additionally, the potent four compounds showed no cytotoxicity at a concentration of 10 μM.

AMIDE COMPOUNDS, THEIR PHARMACEUTICAL COMPOSITIONS, THEIR PREPARATION METHOD AND THEIR USES

The present invention pertains to the field of pharmaceutical chemistry and discloses 8-(3-aminopropyl)-3-exo-8-azabicyclo[3.2.1]octane-3-amino amide compounds represented by formula I, the pharmaceutical compositions, the preparation method and the use thereof. Such compounds or pharmaceutically acceptable salts thereof can be used as an antagonist of CCR5 in preparing medicaments for treating diseases mediated by CCR5, particularly HIV infection, asthma, rheumatoid arthritis, autoimmune diseases and chronic obstructive pulmonary diseases (COPD).

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

HETEROCYCLIC ANTIVIRAL COMPOUNDS

Chemokine receptor antagonists, in particular, 3,7-diazabicyclo [3.3.0] octane compounds according to formula (I) are antagonists of chemokine CCR5 receptors which are useful for treating or preventing an human immunodeficiency virus (HIV) infection, or treating AIDS or ARC. The invention further provides methods for treating diseases that are allieviated with CCR5 antagonists. The invention includes pharmaceutical compositions and methods of using the compounds for the treatment of these diseases. The invention further includes processes for the preparation of compounds according to formula (I).

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.

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).