293744-34-0

Upstream product

• 15110-95-9 N-benzylidene-2-bromobenzenamine 
• 71687-81-5 N-benzyl-2-bromoaniline 
• 615-36-1 2-bromoaniline 
• 118753-70-1 N-(tert-butyloxycarbonyl)bis(2-chloroethyl)amine 
• 252882-60-3 tert-butyl 2-oxo-1,2-dihydro-1'H-spiro[indole-3,4-piperidine]-1'-carboxylate 
• 620-05-3 iodomethylbenzene 
• 59-48-3 2-oxoindole 
• 293744-26-0 tert-butyl 4-{[(2-bromophenyl)amino]carbonyl}piperidine-1-carboxylate 
• 280115-99-3 tert-butyl 4-(chlorocarbonyl)-piperidine-1-carboxylate 
• 84358-13-4 N-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid 
• 100-44-7 benzyl chloride 
• 100-52-7 benzaldehyde 
• 293744-31-7 tert-butyl 4-{[(benzyl)(2-bromophenyl)amino]carbonyl}piperidine-1-carboxylate 

Downstream Products

• 916445-11-9 1-benzyl-spiro[indoline-3,4'-piperidin]-2-one 
• 252882-60-3 tert-butyl 2-oxo-1,2-dihydro-1'H-spiro[indole-3,4-piperidine]-1'-carboxylate 

Relevant academic research and scientific papers

PYRIDYL PIPERIDINES

The invention provides novel substituted pyridyl piperidine compounds according to Formula (I) which are Wnt pathway inhibitors, their manufacture and use for the treatment of hyperproliferative diseases such as cancer, inflammatory or degenerative diseases.

1,3,8-triazaspiro[4.5]decane-2,4-diones as efficacious pan-inhibitors of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) for the treatment of anemia

The discovery of 1,3,8-triazaspiro[4.5]decane-2,4-diones (spirohydantoins) as a structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of enzymes for the treatment of anemia is described. The initial hit class, spirooxindoles, was identified through affinity selection mass spectrometry (AS-MS) and optimized for PHD2 inhibition and optimal PK/PD profile (short-acting PHDi inhibitors). 1,3,8-Triazaspiro[4.5]decane-2,4-diones (spirohydantoins) were optimized as an advanced lead class derived from the original spiroindole hit. A new set of general conditions for C-N coupling, developed using a high-throughput experimentation (HTE) technique, enabled a full SAR analysis of the spirohydantoins. This rapid and directed SAR exploration has resulted in the first reported examples of hydantoin derivatives with good PK in preclinical species. Potassium channel off-target activity (hERG) was successfully eliminated through the systematic introduction of acidic functionality to the molecular structure. Undesired upregulation of alanine aminotransferese (ALT) liver enzymes was mitigated and a robust on-/off-target margin was achieved. Spirohydantoins represent a class of highly efficacious, short-acting PHD1-3 inhibitors causing a robust erythropoietin (EPO) upregulation in vivo in multiple preclinical species. This profile deems spirohydantoins as attractive short-acting PHDi inhibitors with the potential for treatment of anemia.

ANTAGONISTS OF PGD2 RECEPTORS

Described herein are compounds and pharmaceutical compositions containing such compounds that antagonize the PGD2 activated chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2). Also described herein are methods of using such CRTH2 antagonists, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2 mediated conditions or diseases.

Novel 3-spirocyclic indolyl derivatives useful as ORL-1 receptor modulators

The present invention is directed to novel 3-spirocyclic indolyl derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by the ORL-1 receptor.

FUSED AND SPIROCYCLE COMPOUNDS AND THE USE THEREOF

The invention relates to fused and spirocycle compounds of Formula (I), or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein R1, R2, Q1-Q3, and Z are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat, prevent or ameliorate a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.

A convenient synthetic route to spiro[indole-3,4'-piperidin]-2-ones

Starting from 1-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid and 2-bromoaniline, the spiro[indole-3,4'-piperidin]-2-one system was obtained in three high-yielding steps: anilide formation, N(1)-protection, and intramolecular cyclization under Pd catalysis as the key reaction. The preparation of the corresponding 2-bromoanilide was studied. In extension, the same sequence was developed with 4-methyl- and 4-nitro-2-bromoaniline. In the key step, the NO2 group led to a rather diminished yield. The transformation of the protected spiro[indole-3,4'-piperidin]-2'one to the corresponding unprotected dihydroindoles is discussed.