38043-08-2

Upstream product

• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 56553-60-7 sodium tris(acetoxy)borohydride 
• 371-40-4 4-fluoroaniline 
• 76-05-1 trifluoroacetic acid 
• 288573-56-8 1-(tert-Butoxycarbonyl)-4-[(4-fluorophenyl)amino]piperidine 

Downstream Products

• 113675-67-5 3-{2-[4-(4-Fluoro-phenylamino)-piperidin-1-yl]-ethyl}-3H-benzo[d][1,2,3]triazin-4-one 
• 923565-67-7 4-(2-(4-((4-fluorophenyl)amino)-1-piperidinyl)-2-oxoethyl)-benzaldehyde 
• 941572-41-4 1-(3-bromo-2-pyridinyl)-N-(4-fluorophenyl)-4-piperidinamine 
• 920510-66-3 1-{[1-(4-{[(3R,5S)-3,5-dimethyl-1-piperazinyl]methyl}phenyl)-1H-imidazol-2-yl]carbonyl}-N-(4-fluorophenyl)-4-piperidinamine 
• 1127440-78-1 phenylmethyl (2S)-4-([4-(2-(4-[(4-fluorophenyl)amino]-1-piperidinyl)-2-oxoethyl)phenyl]methyl)-2-methyl-1-piperazinecarboxylate 
• 1127440-83-8 1,1-dimethylethyl (2R,6S)-4-([4-(2-(4-[(4-fluorophenyl)amino]-1-piperidinyl)-1-methyl-2-oxoethyl)phenyl]methyl)-2,6-dimethyl-1-piperazinecarboxylate 
• 923565-84-8 N-(4-fluorophenyl)-1-[3-(4-methylphenyl)propanoyl]-4-piperidinamine 
• 923565-83-7 [4-(3-(4-[(4-fluorophenyl)amino]-1-piperidinyl)-3-oxopropyl)phenyl]methanol 
• 923565-82-6 4-(3-(4-((4-fluorophenyl)amino)-1-piperidinyl)-3-oxopropyl)-benzaldehyde 
• 920511-31-5 2-({4-[(4-fluorophenyl)amino]-1-piperidinyl}carbonyl)-3-pyridinol 
• 920511-03-1 (3R,5S)-3,5-Dimethyl-1-({4-[2-({4-[(4-fluorophenyl)amino]piperidin-1-yl}carbonyl)pyridin-3-yl]phenyl}methyl)-4-tert-butoxycarbonyl-piperazine 
• 1127440-21-4 (3R,5S)-3,5-dimethyl-1-({4-[2-({4-[(4-fluorophenyl)amino]piperidin-1-yl}carbonyl)pyridin-3-yl]phenyl}methyl)piperazine 
• 1127440-87-2 1,1-dimethylethyl (2R,6S)-4-([4-(2-(4-[(4-fluorophenyl)-amino]-1-piperidinyl)-1,1-dimethyl-2-oxoethyl)phenyl]methyl)-2,6-dimethyl-1-piperazinecarboxylate 

Relevant academic research and scientific papers

Dual targeting of acetylcholinesterase and tau aggregation: Design, synthesis and evaluation of multifunctional deoxyvasicinone analogues for Alzheimer's disease

Development of multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for Alzheimer's disease (AD). Herein, we reported a new series of deoxyvasicinone analogues as dual inhibitor of acetylcholinesterase (AChE) and tau aggregation that function as multitargeted ligands for AD. All the multitargeted ligands 11(a-j) and 15(a-g) were designed, synthesized, and validated by 1HNMR, 13CNMR and mass spectrometry. All the synthesized compounds 11(a-j) and 15(a-g) were screened for their ability to inhibit AChE, BACE1, amyloid fibrillation, α-syn aggregation, and tau aggregation. All the screened compounds possessed weak inhibition of BACE-1, Aβ42 and α-syn aggregation. However, several compounds were identified as potential hits in the AChE inhibitory screening assay and cellular tau aggregation screening. Among all compounds, 11f remarkably inhibited AChE activity and cellular tau oligomerization at single-dose screening (10 μM). Moreover, 11f displayed a half-maximal inhibitory concentration (IC50) value of 0.91 ± 0.05 μM and half-maximal effective concentration (EC50) value of 3.83 ± 0.51 μM for the inhibition of AChE and cellular tau oligomerization, respectively. In addition, the neuroprotective effect of 11f was determined in tau-expressing SH-SY5Y cells incubated with Aβ oligomers. These findings highlighted the potential of 11f to function as a multifunctional ligand for the development of promising anti-AD drugs.

Discovery of N-(3-fluorophenyl)-1-[(4-([(35)-3-methyl-1-piperazinyl]methyl) phenyl)acetyl]-4-piperidinamine (GSK962040), the first small molecule motilin receptor agonist clinical candidate

N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl) acetyl]-4-piperidinamine 12 (GSK962040) is a novel small molecule motilin receptor agonist. It possesses excellent activity at the recombinant human motilin receptor and also at the native rabbit motilin receptor where its agonist activity results in potentiation of the amplitude of neuronal-mediated contractions of isolated gastric antrum tissue. Compound 12 also possesses highly promising pharmacokinetic profiles in both rat and dog, and these results, in combination with further profiling in human native tissue and an in vivo model of gastrointestinal transit in the rabbit, have led to its selection as a candidate for further development.

The discovery of biaryl carboxamides as novel small molecule agonists of the motilin receptor

Optimisation of urea (5), identified from high throughput screening and subsequent array chemistry, has resulted in the identification of pyridine carboxamide (33) which is a potent motilin receptor agonist possessing favourable physicochemical and ADME profiles. Compound (33) has demonstrated prokinetic-like activity both in vitro and in vivo in the rabbit and therefore represents a promising novel small molecule motilin receptor agonist for further evaluation as a gastroprokinetic agent.

Piperazine Heteroaryl Derivatives as Gpr38 Agonists

The invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, Z, X and B are as defined in the specification. The compounds are partial or full agonists at the GPR38 receptor. Pharmaceutical compositions comprising the compounds, methods of preparing the compounds, uses of the compounds and methods involving the compounds are also provided.

BIARYL COMPOUNDS USEFUL AS AGONISTS OF THE GPR38 RECEPTOR

The present invention relates to novel biaryl derivatives such as compounds of formula (I), which have activity as agonists of the GPR38 receptor and the use of such compounds or pharmaceutical compositions thereof in the treatment of gastrointestinal dis

PIPERAZINE HETEROARYL DERIVATES AS GPR38 AGONISTS

The invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof, (I) wherein R1, R2, R3, R4, R5, R6, Z, X and B are as defined in the specification. The compounds are partial or full agonists at the GPR38 receptor. Pharmaceutical compositions comprising the compounds, methods of preparing the compounds, uses of the compounds and methods involving the compounds are also provided.

BENZYLPIPERAZINE DERIVATIVES AS MOTILIN RECEPTOR ANTAGONISTS

The invention relates to compounds of formula (I) processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of conditions or disorders which are mediated via the GPR38 receptor.

Novel compounds

The invention provides compounds of general formula (I) wherein Q, R, R2, R4, R5, R6, R7 and R8 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.