1024605-91-1

Upstream product

• 699-92-3 1-(3-fluoro-2-hydroxyphenyl)-ethanone 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 

Downstream Products

• 1245738-13-9 (±)-8-fluoro-4-hydroxy-N-[4-(trifluoromethoxy)phenyl]-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxamide 
• 1245738-06-0 (±)-8-fluoro-4-hydroxy-N-[4-(trifluoromethyl)phenyl]-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxamide 
• 1245738-61-7 8-fluoro-4-oxo-N-[4-(trifluoromethyl)phenyl]-3,4-dihydrospiro[chromene-2,4'-piperidine]-1'-carboxamide 

Relevant academic research and scientific papers

Spiro compounds, preparation method thereof, intermediate, pharmaceutical composition and application

The invention discloses a spiro compound as shown in a formula I, a pharmaceutically acceptable salt, a hydrate, a solvate, an optical isomer or a prodrug of the spiro compound, as well as a preparation method, an intermediate, a pharmaceutical composition and an application of the spiro compound. The spiro compound disclosed by the invention has the activity of serving as protein kinase inhibitors and tyrosine kinase inhibitors such as c-Met, and the spiro compound can be used for treating diseases caused by the abnormal activity of kinases, such as cancer, or used for preparing medicaments for treating the diseases.

Synthesis and pharmacological evaluation of novel N-aryl-3,4-dihydro- 1′H-spiro[chromene-2,4′-piperidine]-1′-carboxamides as TRPM8 antagonists

A novel series of N-aryl-3,4-dihydro-1′H-spiro[chromene-2,4′- piperidine]-1′-carboxamides was identified as transient receptor potential melastatin 8 (TRPM8) channel blockers through analogue-based rational design, synthesis and screening. Details of the synthesis, effect of aryl groups and their substituents on in-vitro potency were studied. The effects of selected functional groups on the 4-position of the chromene ring were also studied, which showed interesting results. The 4-hydroxy derivatives showed excellent potency and selectivity. Optical resolution and screening of alcohols revealed that (R)-(-)-isomers were in general more potent than the corresponding (S)-(+)-isomers. The isomer (R)-(-)-10e (IC50: 8.9 nM) showed a good pharmacokinetic profile upon oral dosing at 10 mg/kg in Sprague-Dawley (SD) rats. The compound (R)-(-)-10e also showed excellent efficacy in relevant rodent models of neuropathic pain.

SPIROCYCLIC PIPERIDINE DERIVATIVES AS TRPM 8 MODULATORS

The present invention provides Transient Receptor Potential subfamily M, member 8 (TRPM8) modulators of formula (I). In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPM8.

Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]

Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis.

4-(Phenylsulfonyl)piperidines: Novel, selective, and bioavailable 5-HT2A receptor antagonists

On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identifed as high-affinity, selective 5-HT2A receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4-(phenylsulfon