72408-57-2

Upstream product

• 60307-42-8 2-(4-Bromo-phenyl)-2-{[1-phenyl-meth-(E)-ylidene]-amino}-propionitrile 
• 6320-50-9 (R,S)-4-(4-bromophenyl)-4-methyl-2,5-dioxoimidazolidine 
• 99-90-1 para-bromoacetophenone 

Downstream Products

• 184427-34-7 (S)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 
• 340188-51-4 (R)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 
• 184426-82-2 [4-(R)-(cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid 
• 184427-37-0 N-((S)-1-(4-bromophenyl)-1-(ethoxycarbonyl)ethyl)-N'-(ethoxy-carbonylmethyl)urea 
• 184426-81-1 2-((S)-4-(4-Cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid 
• 177563-40-5 3-{2-[4-(R)-(4-aminoiminomethyl-phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl]acetylamino}-3-(S)-phenylpropionic acid ethyl ester 
• 177563-40-5 3-{2-[4-(R)-(4-aminoiminomethyl-phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl]acetylamino}-3-(R)-phenylpropionic acid ethyl ester 
• 177563-40-5 (S)-3-{2-[(S)-4-(4-Carbamimidoyl-phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl]-acetylamino}-3-phenyl-propionic acid ethyl ester 
• 177563-40-5 3-{2-[4-(S)-(4-aminoiminomethyl-phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl]acetylamino}-3-(R)-phenylpropionic acid ethyl ester 
• 184427-38-1 2-((S)-4-(4-bromophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid 

Relevant academic research and scientific papers

(4-HYDROXYPYRROLIDIN-2-YL)-HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF

The present disclosure relates to bifunctional compounds of formula (I), which can be used as modulators of targeted ubiquitination. In particular, the present disclosure is directed to compounds which contain on one end a VHL ligand moiety, which binds to the VHL E3 ubiquitin ligase, and on the other end a moiety that binds a target protein such that degradation of the target protein/polypeptide is effectuated. Also disclosed are VHL ligands of formula (III).

Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists

2-Aminooxazolines were discovered as a novel structural class of TAAR1 ligands. Starting from a known adrenergic compound 1, structural modifications were made to obtain highly potent and selective TAAR1 ligands such as 12 (RO5166017), 18 (RO5256390), 36 (RO5203648), and 48 (RO5263397). These compounds exhibit drug-like physicochemical properties, have good oral bioavailability, and display in vivo activity in a variety of animal models relevant for psychiatric diseases and addiction.

ANTIVIRAL COMPOUNDS

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

BMS-201620: A selective beta 3 agonist

A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human β3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent β3 full agonist (Ki=93nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation.

Discovery of an orally active non-peptide fibrinogen receptor antagonist based on the hydantoin scaffold

Antagonists of the platelet fibrinogen receptor (GP IIb/IIIa receptor) are expected to be a promising new class of antithrombotic agents. The binding of fibrinogen to the fibrinogen receptor depends on an Arg-Gly-Asp-Ser (RGDS) tetrapeptide recognition motif. Structural modifications of the RGDS lead have led to the discovery of a non-peptide RGD mimetic GP IIb/IIIa antagonist 44 (S 1197). Compound 44 inhibited, in a dose dependent and reversible manner, human and dog platelet aggregation as well as 125I-fibrinogen binding to ADP-activated human gel filtered platelets and isolated GP IIb/IIIa with Ki values of 9 nM and 0.17 nM, respectively. A pharmacophore mapping procedure with QXP and a 3D-QSAR analysis applying the GRID/GOLPE methodology yielded a stable, rather predictive model and revealed structural features which are important for binding. Hydrophobic substitutions both at the hydantoin nucleus and at the C-terminus increase the affinity toward the fibrinogen receptor. The crystalline ethyl ester prodrug 48 (HMR 1794) is an orally active antithrombotic agent which is a promising drug candidate for the treatment of thrombotic diseases in humans.

Hydantoin compounds, salts thereof, processes for their preparation, and processes for preparing pharmaceutically active compounds comprising them

The present invention relates to hydantoin derivatives of the formula I STR1 and which are intermediates for the preparation of pharmaceutical active compounds, their preparation and their use in the preparation of the active compounds.

From Peptides to Heterocyclic Peptide Mimetics - Design and Synthesis of an Orally Active Fibrinogen Receptor Antagonist for the Prevention of Thrombosis

The binding of fibrinogen to the platelet fibrinogen receptor (GP IIb/IIIa receptor) depends on an Arg-Gly-Asp-Ser (RGDS) tetrapeptide recognition motif.Structural modifications of the RGDS tetrapeptide lead structure has led to the discovery of a non-peptide RGD mimetic GP IIb/IIIa antagonist 1 (S 1197).Compound 1 inhibited dose-dependently and reversibly human platelet aggregation.In conscious dogs the ethyl ester prodrug 2 (S 5740) showed a high plasma availability of the active moiety of 42+/-8percent (n=4) and a plasma half life of 9.9 hours after oral administration as measured by bioassay.Compound 2 may potentially be used for chronic treatment and prophylaxis of thrombotic diseases in humans.A pilot plant synthesis of compound 2 was developed.