297773-47-8

Upstream product

• 113118-81-3 5-bromopyridine-3-carbaldehyde 
• 141-82-2 malonic acid 

Downstream Products

• 1423134-22-8 (3S)-3-[5-(4-fluoro-3-nitrophenyl)pyridin-3-yl]-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid 
• 1423135-11-8 3-{[(3R)-1-(3-{1-[(tert-butoxy)carbonyl]piperidin-4-yl}propanoyl)piperidin-3-yl]formamido}-3-[5-(4-fluoro-3-nitrophenyl)pyridin-3-yl]propanoic acid 
• 1423135-10-7 tert-butyl 4-{3-[(3R)-3-({1-[5-(4-fluoro-3-nitrophenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate 
• 1423134-21-7 (3S)-3-[5-(4-cyano-3-fluorophenyl)pyridin-3-yl]-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid 
• 1423135-09-4 3-({[(3R)-1-{3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propan oyl}piperidin-3-yl]carbonyl}amino)-3-[5-(4-cyano-3-fluorophenyl)pyridin-3-yl]propanoic acid 
• 1423135-06-1 tert-butyl 4-{3-[(3R)-3-({1-[5-(4-cyano-3-fluorophenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate 
• 1423134-20-6 (3S)-3-[5-(3-cyano-4-fluorophenyl)pyridin-3-yl]-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid 
• 1423135-03-8 3-({[(3R)-1-{3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propanoyl}piperidin-3-yl]carbonyl}amino)-3-[5-(3-cyano-4-fluorophenyl)pyridin-3-yl]propanoic acid 
• 1423135-00-5 tert-butyl 4-{3-[(3R)-3-({1-[5-(3-cyano-4-fluorophenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate 
• 1423134-97-7 3-({[(3R)-1-{3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propanoyl}piperidin-3-yl]carbonyl}amino)-3-{5-[2-(2-fluoroethoxy)phenyl]pyridin-3-yl}propanoic acid 
• 1423134-94-4 tert-butyl 4-(3-{(3R)-3-[(1-{5-[2-(2-fluoroethoxy)phenyl]pyridin-3-yl}-3-methoxy-3-oxopropyl)carbamoyl]piperidin-1-yl}-3-oxopropyl)piperidine-1-carboxylate 
• 1423134-93-3 tert-butyl 4-{3-[(3R)-3-({1-[5-(2-hydroxyphenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate 
• 1423134-19-3 (3S)-3-{5-[2-(2-fluoroethoxy)phenyl]pyridin-3-yl}-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid 
• 1423134-18-2 (3S)-3-{5-[4-(2-fluoroethoxy)phenyl]pyridin-3-yl}-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid 

Relevant academic research and scientific papers

An expedient method for resolution of 3-amino-3-(3′-pyridyl)propionic acid and related compounds

Preparation of methyl (S)-3-amino-3-(3′-pyridyl)propionate dihydrochloride in high enantiomeric purity by selective crystallization of a diastereomeric salt of a carboxylic acid precursor (W-BOC-protected) with (1R,2S)-(-)-ephedrine is described. Further demonstration of the usefulness of this procedure to resolve other 3-amino-3-[(substituted)pyridyl]propionic acids is also described.

ANTAGONISTS OF HUMAN INTEGRIN (ALPHA4)(BETA7)

Disclosed are small molecule antagonists of α4β7 integrin, and methods of using them to treat a number of specific diseases or conditions.

COMPOUNDS FOR BINDING TO THE PLATELET SPECIFIC GLYCOPROTEIN IIB/IIIA AND THEIR USE FOR IMAGING OF THROMBI

The present invention relates to novel fluorine containing compounds, methods for their preparation, the intermediates of the synthesis, their use as diagnostic agents, especially for imaging of thrombi. The invention relates to positron emission tomography (PET) agents and associated precursor reagents, and methods for producing such radiolabeled agents for imaging of thrombi in a mammalian body. More particulariy, the invention relates to small, nonpeptide, high-affinity, specific-binding glycoprotein llb/IIIa antagonists for imaging of thrombi.

Potent, orally active GPIIb/IIIa antagonists containing a nipecotic acid subunit. Structure-activity studies leading to the discovery of RWJ-53308

Although intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-activity surrounding the prototype fibrinogen receptor antagonist RWJ-50042 (racemate of 1), which was derived from a unique approach involving the γ-chain of fibrinogen (Hoekstra et al. J. Med. Chem. 1995, 38, 1582). Our analogue studies culminated in the discovery of RWJ-53308 (2), a potent, orally active GPIIb/IIIa antagonist. To progress from RWJ-50042 to a suitable candidate for clinical development, we conducted a series of optimization cycles that employed solid-phase parallel synthesis for the rapid, efficient preparation of nearly 250 analogues, which were assayed for fibrinogen receptor affinity and inhibition of platelet aggregation induced by four different activators. This strategy produced several promising analogues for advanced study, including 3-(3,4- methylenedioxybenzene)-β-amino acid analogue 3 (significant improved in vivo potency) and 3-(3-pyridyl)-β-amino acid 2 (significantly improved potency, oral absorption, and duration of action). In dogs, 2 displayed significant ex vivo antiplatelet activity on oral administration at 1.0 mg/kg, 16% systemic oral bioavailability, minimal metabolic transformation, and an excellent safety profile. Additionally, 2 was found to be efficacious in three in vivo thrombosis models: canine arteriovenous (AV) shunt (0.01-0.1 mg/kg, iv), guinea pig photoactivation-induced injury (0.3-3 mg/kg, iv), and guinea pig ferric chloride-induced injury (0.3-1 mg/kg, iv). On the basis of its noteworthy preclinical data, RWJ-53308 (2) was selected for clinical evaluation.