897932-58-0

Upstream product

• 34619-03-9 tert-butyldicarbonate 
• 2516-47-4 cyclopropanemethylamine 
• 5163-20-2 N-methylcyclopropylamine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 132844-48-5 Cyclopropylcarbamic acid t-butyl ester 
• 74-88-4 methyl iodide 

Downstream Products

• 67376-94-7 methylcyclopropylamine hydrochloride 
• 1620683-39-7 (Z)-tert-butyl (cyclopropylmethyl)(3-(p-tolyl)prop-1-en-1-yl)carbamate 

Relevant academic research and scientific papers

Conformational Aspects in the Design of Inhibitors for Serine Hydroxymethyltransferase (SHMT): Biphenyl, Aryl Sulfonamide, and Aryl Sulfone Motifs

Malaria remains a major threat to mankind due to the perpetual emergence of resistance against marketed drugs. Twenty-one pyrazolopyran-based inhibitors bearing terminal biphenyl, aryl sulfonamide, or aryl sulfone motifs were synthesized and tested towards serine hydroxymethyltransferase (SHMT), a key enzyme of the folate cycle. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target, as well as PfNF54 strains in cell-based assays in the low nanomolar range (18–56 nm). Seven co-crystal structures with P. vivax (Pv) SHMT were solved at 2.2–2.6 ? resolution. We observed an unprecedented influence of the torsion angle of ortho-substituted biphenyl moieties on cell-based efficacy. The peculiar lipophilic character of the sulfonyl moiety was highlighted in the complexes with aryl sulfonamide analogues, which bind in their preferred staggered orientation. The results are discussed within the context of conformational preferences in the ligands.

NOVEL COMPOUNDS

The present invention relates to novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.

Palladium-catalyzed γ-selective arylation of zincated Boc-allylamines

The regio- and diastereoselective arylation of Boc-protected allylamines was performed via a one-pot lithiation/transmetalation to zinc/cross-coupling sequence, through an appropriate choice of a phosphine ligand. A variety of γ-arylated products were obtained in moderate to good yield, and the products could be directly transformed into valuable γ-arylamines and β-aryl aldehydes.

SUBSTITUTED PYRAZOLO[1,5-A] PYRIDINE AS TROPOMYOSIN RECEPTOR KINASE (TRK) INHIBITORS

The present application relates to a series of substituted pyrazolo[1,5-a]pyridine compounds, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.

SUBSTITUTED PYRAZOLO[1,5-A] PYRIDINE AS TROPOMYOSIN RECEPTOR KINASE (TRK) INHIBITORS

The present application relates to a series of substituted pyrazolo[1,5-a]pyridine compounds, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors., method of making and pharmaceutical compositions comprising such compounds.

NOVEL 2-PIPERIDIN-1-YL-ACETAMIDE COMPOUNDS FOR USE AS TANKYRASE INHIBITORS

The present invention provides for compounds of formula (I), wherein R1-R5 and L are defined herein. The present invention also provides for pharmaceutical compositions and combinations comprising a compound of formula (I) as well as for the use of such compounds as tankyrase inhibitors and in the treatment of Wnt signaling and tankyrase 1 and 2 signaling related disorders which include, but are not limited to, cancer.

Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor

Currently, a lack of sufficient tools has limited the understanding of the relationship between neuropsychiatric disorders and the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor. Herein, we describe the discovery and development of an antagonist NOP receptor occupancy (RO) tracer and a novel positron emission tomography (PET) radioligand suitable to probe the NOP receptor in human clinical studies. A thorough structure-activity relationship (SAR) around the high-affinity 3-(2′-fluoro-4′,5′- dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-yl)-2-(2-halobenzyl) -N-alkylpropanamide scaffold identified a series of subnanomolar, highly selective NOP antagonists. Subsequently, these unlabeled NOP ligands were evaluated in vivo by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in rat to determine brain uptake, kinetics and specific binding. (S)-27 was identified as a suitable unlabeled preclinical RO tracer to accurately quantify NOP receptor engagement in rat brain. Three compounds were selected for evaluation in nonhuman primates as PET tracers: (-)-26, (-)-30, and (-)-33. Carbon-11 labeling of (+)-31 yielded [11C]-(S)-30, which exhibited minimal generation of central nervous system (CNS) penetrant radiometabolites, improved brain uptake, and was an excellent PET radioligand in both rat and monkey. Currently [11C]-(S)-30 is being evaluated as a PET radiotracer for the NOP receptor in human subjects.

N-boc protection of amines with di-tert-butyldicarbonate in water under neutral conditions in the presence of β-cyclodextrin

A new protocol for protection of aryl and aliphatic amines was developed with (Boc)2O in the presence of β-cyclodextrin in water. A catalytic amount of β-cyclodextrin is specific for activation of amines. This procedure works well on a wide variety of both electron-rich and electron-deficient amines. Georg Thieme Verlag Stuttgart.