301219-96-5

Upstream product

• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 10315-07-8 N-benzylpiperidine-4-carboxylic acid 
• 160809-37-0 N-methoxy-N-methyl-piperidine-4-carboxamide 
• 100-39-0 benzyl bromide 
• 10315-06-7 1-benzylpiperidine-4-carboxylic acid methyl ester 

Downstream Products

• 88796-04-7 4-acetyl-1-benzylpiperidine 
• 1372809-44-3 (1-benzylpiperidin-4-yl)-(2-methoxy-3-hydroxyphenyl)methanone 
• 1372809-46-5 C₁₃H₁₉NO₆S 
• 1372809-45-4 C₂₀H₂₃NO₆S 
• 1372809-43-2 (1-benzylpiperidin-4-yl)-(2-methoxy-3-triisopropylsilanyloxyphenyl)methanone 
• 1435892-94-6 2-(1-benzylpiperidin-4-yl)-4H-quinolizin-4-one 
• 1435892-64-0 1-(1-benzylpiperidin-4-yl)-2-(pyridin-2-yl)ethanone 

Relevant academic research and scientific papers

Non-substrate based, small molecule inhibitors of the human isoprenylcysteine carboxyl methyltransferase

Activating mutations of human K-Ras proteins are among the most common oncogenic mutations, present in approximately 30% of all human cancers. Posttranslational modifications to K-Ras guide it to the plasma membrane and disruption of this localization inhibits the growth of Ras-driven cancers. The human isoprenylcysteine carboxyl methyltransferase (hIcmt) enzyme catalyzes the final α-carboxyl methylesterification of the C-terminal farnesyl cysteine of K-Ras, which is necessary for its proper localization. Thus, hIcmt inhibition is a regarded as a promising cancer therapy. A high quality inhibitor of hIcmt with in vivo activity would advance hIcmt research and drug development. Herein, Wwe report the results of a screen for small molecule hIcmt inhibitors in a library of molecules that were not hIcmt substrate analogs. The lead compound identified by this screen (1) was modified to remove chemical liabilities and to increase potency. The most potent resulting compound (5) inhibited hIcmt in vitro with low micromolar potency (IC50 = 1.5 ± 0.2 μM) and was kinetically characterized as a competitive inhibitor for prenylated substrates and a non-competitive inhibitor for the cofactor and methyl donor S-adenosylmethionine (SAM). These inhibitors offer important structure activity relationships for the future development of hIcmt inhibitors with in vivo activity.

Synthesis of functionalised 4H-quinolizin-4-ones via tandem Horner-Wadsworth-Emmons olefination/cyclisation

4H-Quinolizin-4-ones are a unique class of heterocycle with valuable physicochemical properties and which are emerging as key pharmacophores for a range of biological targets. A tandem Horner-Wadsworth-Emmons olefination/cyclisation method has been developed to allow facile access to substituted 4H-quinolizin-4-ones encoded with a range of functional groups.

PYRAZINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS

Pyrazine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

SUBSTITUTED 1-AMINOPHTHALAZINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC APPLICATION THEREOF

The invention concerns 1-amino-phthalazine derivatives of general formula (I): Wherein A, B, L, R, R1, R2, R3, R4, R5 and R7 are as defined herein. The invention also concerns the preparation of said compounds and their therapeutic use.