6320-50-9

Usage

Chemical compound

5-(4-Bromophenyl)-5-methylimidazolidine-2,4-dione

Class

Imidazolidinediones

Physical form

White crystalline solid

Molecular weight

257.09 g/mol

Uses

Organic synthesis, pharmaceutical research

Pharmacological properties

Anticonvulsant, antiepileptic

Investigated for potential use in

Treatment of neurodegenerative diseases and cognitive disorders

InChI:InChI=1/C10H9BrN2O2/c1-10(8(14)12-9(15)13-10)6-2-4-7(11)5-3-6/h2-5H,1H3,(H2,12,13,14,15)/t10-/m1/s1

Upstream product

• 151-50-8 potassium cyanide 
• 99-90-1 para-bromoacetophenone 
• 143-33-9 sodium cyanide 
• 506-87-6 ammonium carbonate 
• 773837-37-9 sodium cyanide 

Downstream Products

• 72408-57-2 (R,S)-2-amino-2-(4-bromophenyl)-propionic acid 
• 184427-34-7 (S)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 
• 766537-46-6 (S)-2-amino-2-(4-bromophenyl)-propionic acid 
• 184427-33-6 (R,S)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 
• 340188-51-4 (R)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 
• 184427-38-1 2-((S)-4-(4-bromophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid 
• 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 
• 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-(R)-(4-aminoiminomethyl-phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl]acetylamino}-3-(R)-phenylpropionic acid ethyl ester 
• 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 
• 184426-81-1 2-((S)-4-(4-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 
• 184426-82-2 [4-(R)-(cyanophenyl)-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).

Identification and Profiling of Hydantoins - A Novel Class of Potent Antimycobacterial DprE1 Inhibitors

Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-β-d-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.

Computer-aided insights into receptor-ligand interaction for novel 5-arylhydantoin derivatives as serotonin 5-HT7 receptor agents with antidepressant activity

This paper presents a computer-aided insight into the receptor-ligand interaction for novel analogs of the lead structure 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione (1, MF-8), as part of the search for potent and selective serotonin 5-HT7 receptor (5-HT7R) agents. New hydantoin derivatives (4-19) were designed and synthesized. For 5-phenyl-3-(2-hydroxy-3-(4-(2-ethoxyphenyl)piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione (4), its crystal structure was determined experimentally. Molecular modeling studies were performed, including both pharmacophore and structure-based approaches. New compounds were investigated in radioligand binding assays (RBA) for their affinity toward 5-HT7R and selectivity over 5-HT1AR, dopamine D2R and α1-, α2-and β-adrenoceptors. Selected compounds (5-8) were assessed for their antidepressant and anxiolytic effects in vivo in mice. Most of the tested compounds displayed potent affinity and selectivity for 5-HT7R in RBA, in particular seven compounds (4, 5, 7, 8 and 10-12, Ki ≤ 10 nM). Antidepressant-like activity in vivo for all tested compounds (5-8) was confirmed. SAR analysis based on both crystallography-supported molecular modeling and RBA results indicated that mono-phenyl substituents at both hydantoin and piperazine are more favorable for 5-HT7R affinity than the di-phenyl ones.

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.

Synthesis and in vivo hypoglycemic activity of new imidazolidine-2,4-dione derivatives

A series of new 3-arylsulfonylimidazolidine-2,4-diones (2a-2p) were synthesized by reacting imidazolidine-2,4-diones (1a-1e) with arylsulfonyl chlorides in the presence of triethyl amine. The imidazolidine-2,4-diones (1a-1e) were in turn synthesized from the corresponding ketones through Bucherer-Bergs reaction. All the synthesized compounds were characterized on the basis of their spectral (IR, 1H and 13C NMR and MS) and microanalytical data. The hypoglycemic activity of the compounds (2a-2p) was evaluated using alloxanized diabetic rat model. Compound 2a showed an excellent activity with a reduction in the blood glucose level of -286 ± 7 mg/dL after 5 h of drug administration as compared to -270 ± 8 mg/dL for glipizide. The hypoglycemic activity of compound 2b (-268 ± 9 mg/dL) was also comparable to the standard drug. However, only moderate activity was observed for compound 2e.

Solvent effects on the absorption spectra of potentially pharmacologically active 5-alkyl-5-arylhydantoins: A structure-property relationship study

To obtain insight into the interactions of potential anticonvulsant drugs with their surrounding, two series of 5-methyl-5-aryl- and 5-ethyl-5- -arylhydantoins were synthesized and their absorption spectra were recorded in the region from 200 to 400 nm in a set of selected solvents. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding interactions on the absorption maxima shifts were analyzed by means of the linear solvation energy relationship (LSER) concept of Kamlet and Taft. The ratio of the contributions of specific and non-specific solvent-solute interactions were correlated with the corresponding absorption, distribution, metabolism, and excretion (ADME) properties of the studied compounds. The correlation equations were combined with different physicochemical parameters to generate new equations, which demonstrate the reasonable relationships between the solvent- solute interactions and the structure-activity parameters. Copyright (C)2013 SCS.

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.

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.