88915-34-8

Upstream product

• 34737-89-8 1-Benzyl-3-methyl-4-piperidon 
• 100-52-7 benzaldehyde 
• 863249-31-4 (3S,4S)-3-methylpiperidin-4-yl pivalate 
• 790667-50-4 trans-1-benzyl-3-methylpiperidin-4-ol 
• 790667-50-4 (3R,4R)-1-benzyl-3-methylpiperidin-4-ol 
• 620165-90-4 (3R,4S)-4-Amino-1-benzyl-3-methyl-piperidin-2-one 
• 309912-49-0 (3S,4R)-1-benzyl-4-(N,N-dibenzylamino)-3-methylpiperidin-2-one 
• 213134-97-5 (3R,4S)-1-benzyl-4-(N,N-dibenzylamino)-3-methylpiperidin-2-one 

Relevant academic research and scientific papers

Discovery of a Potent and Selective CCR4 Antagonist That Inhibits Treg Trafficking into the Tumor Microenvironment

Recruitment of suppressive CD4+ FOXP3+ regulatory T cells (Treg) to the tumor microenvironment (TME) has the potential to weaken the antitumor response in patients receiving treatment with immuno-oncology (IO) agents. Human Treg express CCR4 and can be recruited to the TME through the CC chemokine ligands CCL17 and CCL22. In some cancers, Treg accumulation correlates with poor patient prognosis. Preclinical data suggests that preventing the recruitment of Treg and increasing the population of activated effector T cells (Teff) in the TME can potentiate antitumor immune responses. We developed a novel series of potent, orally bioavailable small molecule antagonists of CCR4. From this series, several compounds exhibited high potency in distinct functional assays in addition to good in vitro and in vivo ADME properties. The design, synthesis, and SAR of this series and confirmation of its in vivo activity are reported.

Synthesis and evaluation of novel 1H-pyrrolo[2,3-b]pyridine-5-carboxamide derivatives as potent and orally efficacious immunomodulators targeting JAK3

Janus kinases (JAKs) regulate various inflammatory and immune responses and are targets for the treatment of inflammatory and immune diseases. As a novel class of immunomodulators targeting JAK3, 1H-pyrrolo[2,3-b]pyridine-5-carboxamide derivatives are promising candidates for treating such diseases. In chemical modification of lead compound 2, the substitution of a cycloalkyl ring for an N-cyanopyridylpiperidine in C4-position was effective for increasing JAK3 inhibitory activity. In addition, modulation of physical properties such as molecular lipophilicity and basicity was important for reducing human ether-a-go-go-related gene (hERG) inhibitory activity. Our optimization study gave compound 31, which exhibited potent JAK3 inhibitory activity as well as weak hERG inhibitory activity. In cellular assay, 31 exhibited potent immunomodulating effect on IL-2-stimulated T cell proliferation. In a pharmacokinetic study, good metabolic stability and oral bioavailability of 31 were achieved in rats, dogs, and monkeys. Further, 31 prolonged graft survival in an in vivo rat heterotopic cardiac transplant model.

CONDENSED PYRIDINE COMPOUND

The present invention provides a compound having excellent JAK3 inhibitory activity and being useful as an active ingredient of an agent for treating and/or preventing various immune diseases including autoimmune diseases, inflammatory diseases, and allergic diseases. As a result of investigations with respect to novel condensed heterocyclic derivatives, the inventors have verified that a condensed pyridine compound has excellent JAK3 inhibitory activity, thereby completing the present invention. More specifically, it has been verified that since the compound according to the present invention has inhibitory activity against JAK3, the compound is useful as an active ingredient of an agent for treating or preventing diseases caused by undesirable cytokine signal transduction (e.g., rejection during live organ/tissue transplantation, autoimmune diseases, asthma, atopic dermatitis, rheumatism, psoriasis and atherosclerotic disease), or diseases caused by abnormal cytokine signal transduction (e.g., cancer and leukemia).

Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments

This invention relates to new generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, to their optical isomers, diastereomers or enantiomers, as well as pharmaceutically acceptable salts, hydrates, prodrugs, polymorphs and pseudopolymorphs thereof, to their preparation, to their compositions and to their use.

CCR8 INHIBITORS

Disclosed are CCR8 inhibitors represented by Structural Formulas (I). The variables in Structural Formula (I) are described herein. Also disclosed are methods of treating a subject with a CCR8 mediated condition, especially asthma, by administering one of the disclosed CCR8 inhibitors to the subject.

CCR8 INHIBITORS

Disclosed is an inhibitor of CCR8 that is represented by Structural Formula (I). Also disclosed are pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent and a CCR8 inhibitor represented by Structural Formula (I). Also disclosed is a method of treating inflammatory disorders in a subject by administering a CCR8 inhibitor to the subject.

Stereocontrolled dopamine receptor binding and subtype selectivity of clebopride analogues synthesized from aspartic acid

Employing the achiral 4-aminopiperidine derivative clebopride as a lead compound, chiral analogues were developed displaying dopamine receptor binding profiles that proved to be strongly dependent on the stereochemistry. Compared to the D1 receptor, the t

2-oxoimidazole derivatives

The present invention relates to a compound represented by Formula [I] wherein represents an aromatic carbo- or heterocyclic ring which may have a substituent; Cy represents a mono-, bi- or tricyclic aliphatic carbocyclic group having 3 to 20 carbon atoms, which may have a substituent; represents a mono- or bicyclic aliphatic nitrogen-containing heterocyclic group having 3 to 14 carbon atoms, which may have a substituent; R1represents a hydrogen atom, a lower alkenyl group, a lower alkynyl group, a cyclo(lower alkyl) group, an amino group, a lower alkylamino group, a di(lower alkyl)-amino group, a hydroxyl group, a lower alkoxy group, a carboxyl group, a lower alkoxycarbonyl group, a carbamoyl group, a lower alkylcarbamoyl group or a di(lower alkyl)carbamoyl group, or a lower alkyl group which may have a substituent; and R2represents a hydrogen atom or a lower alkyl group, a salt or ester thereof, a production process for the same, and an analgesic, a reliever against tolerance to a narcotic analgesic represented by morphine, a reliever against dependence on a narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a remedy for schizophrenia, a remedy for Parkinsonism, a remedy for chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension, comprising an effective ingredient of the same.