41221-47-0

Usage

Chemical Properties

OFF-WHITE TO LIGHT BROWN CRYSTALLINE SOLID

InChI:InChI=1/C9H7NO3/c1-13-9(12)7-3-2-4-8(5-7)10-6-11/h2-5H,1H3

Upstream product

• 2905-65-9 methyl 3-chlorobenzoate 
• 917-61-3 sodium isocyanate 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 92146-82-2 tert-butyl 3-aminobenzoate 
• 99-05-8 meta-aminobenzoic acid 
• 87360-24-5 3-amino-benzoic acid methyl ester hydrochloride 
• 618-95-1 methyl 3-nitrobenzoate 
• 4518-10-9 Methyl 3-aminobenzoate 
• 503-38-8 trichloromethyl chloroformate 
• 1877-71-0 benzene 1,3-dicarboxylic acid monomethyl ester 
• 75-44-5 phosgene 

Downstream Products

• 131450-03-8 3-(3-{(S)-5-[(S)-2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-5-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-2-carboxy-ethylcarbamoyl]-pentyl}-ureido)-benzoic acid methyl ester 
• 590392-95-3 C₂₄H₃₃N₃O₃ 
• 1428147-68-5 C₁₆H₁₄N₂O₅ 
• 938467-58-4 3-[3-(3,3-diphenylpropyl)-3-(2-morpholin-4-ylethyl)ureido]benzoic acid 
• 1429206-35-8 C₃₁H₃₇N₃O₄ 
• 1429206-36-9 C₃₁H₃₈N₄O₃ 
• 1429206-37-0 C₃₂H₄₀N₄O₃ 
• 212701-37-6 3-({(S)-2-[(S)-1-(Benzyl-methyl-carbamoyl)-2-naphthalen-2-yl-ethylcarbamoyl]-pyrrolidine-1-carbonyl}-amino)-benzoic acid methyl ester 
• 154063-69-1 3-{3-[2-Oxo-1-(2-oxo-2-o-tolyl-ethyl)-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-ureido}-benzoic acid methyl ester 

Relevant academic research and scientific papers

Investigating Bicyclobutane-Triazolinedione Cycloadditions as a Tool for Peptide Modification

Acyl bicyclobutanes are shown to engage in strain-promoted cycloaddition reactions with a diverse array of triazolinedione reagents. The synthesis of an orthogonally protected urazole building block enabled the facile preparation of amino acid- and peptid

New potent calcimimetics: I. Discovery of a series of novel trisubstituted ureas

Starting from Fendiline and R-568, we identified a novel series of urea compounds as positive allosteric modulators of the calcium sensing receptor (CaSR), as part of a program to identify novel therapeutics for secondary hyperparathyroidism. Initially id

Inhibitors of Dengue virus and West Nile virus proteases based on the aminobenzamide scaffold

Dengue and West Nile viruses (WNV) are mosquito-borne members of flaviviruses that cause significant morbidity and mortality. There is no approved vaccine or antiviral drugs for human use to date. In this study, a series of functionalized meta and para aminobenzamide derivatives were synthesized and subsequently screened in vitro against Dengue virus and West Nile virus proteases. Four active compounds were identified which showed comparable activity toward the two proteases and shared in common a meta or para(phenoxy)phenyl group. The inhibition constants (Ki) for the most potent compound 7n against Dengue and West Nile virus proteases were 8.77 and 5.55 μM, respectively. The kinetics data support a competitive mode of inhibition of both proteases by compound 7n. This conclusion is further supported by molecular modeling. This study reveals a new chemical scaffold which is amenable to further optimization to yield potent inhibitors of the viral proteases via the combined utilization of iterative medicinal chemistry/structure-activity relationship studies and in vitro screening.

Palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate: A practical synthesis of unsymmetrical ureas

An efficient method for palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate is reported. The protocol allows for the synthesis of unsymmetrical N,N'-di- and N,N,N'-trisubstituted ureas in one pot and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation was gleaned through studies of the transmetalation and reductive elimination steps of the reaction, including the first demonstration of reductive elimination from an arylpalladium isocyanate complex to produce an aryl isocyanate.

CHEMOKINE RECEPTOR BINDING COMPOUNDS

The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. Thesd compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

Organosilicon synthesis of isocyanates: III. Synthesis of aliphatic, carbocyclic, aromatic, and alkylaromatic isocyanatocatboxylic acid esters

A series of aminoacid esters was prepared by treating the aminoacid suspensions in ethanol with thionyl chloride. Best conversion of aminoacid esters to corresponding isocyanates was achieved in the case of aromatic and carbocyclic aminoesters by phosgeneation of their N-silyl derivatives, and in the case of aliphatic and alkylaromatic aminoesters by phosgeneation of O-silyl or N,O-bissilylurethanes on their basis. In the last case additional step of esterification of the by-products isocyanatoalkylcarboxylic acid chlorides is required after phosgeneation. Unusual generation of cynnamates and intramolecular N→O-migration of trimethylsilyl group in the solutions of silylated alkylaromatic β-aminoacid esters were found. Pleiades Publishing, Inc., 2006.

2-Nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N- methylamide (SDZ NKT 343), a potent human NK1 tachykinin receptor antagonist with good oral analgesic activity in chronic pain models

A lead compound which had sub-micromolar affinity for the rabbit NK1 receptor but negligible affinity for rat NK1 receptors, 3a, was discovered by directed screening. 2-Substitution in the ring of the benzylthiourea substituent in the initial lead was found to be important, and halogens (Cl, Br) in this position were found to improve affinity for the human receptor. The activity of a series of 2-halo-substituted benzylthioureas was then optimized by modification of the proline diphenylmethyl amide, guided by a simple conceptual model based on structural overlay between these early antagonists and NK1 selective peptides. In this way, aromatic amino acid amides were identified which had improved affinity with respect to the starting diphenylmethyl (DPM) amides. The first sub-nanomolar ligand for the human NK1 receptor which arose from this series, 4af, combined a 2- chlorobenzylthiourea unit with a 2-naphthylalanine amide. Contemporaneously it was discovered that the benzylthiourea unit could be simplified to a phenylthiourea providing that an appropriate 2-substituent was also incorporated. Combination of these two series gave 2-NO2 phenylthiourea analogues which led directly to the analogous urea, 5f (2- nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzy-N- methylamide, SDZ NKT 343), a highly potent ligand for the human NK1 receptor (K(i) = 0.16 nM). In addition to its high in vitro potency, 5f proved to be a potent orally active analgesic in guinea pig models of chronic inflammatory and neuropathic pain. The nature of the 2-aryl substituent was found to be critical for oral activity in this series. Clinical evaluation of 5f as a novel analgesic agent is currently underway.

Biological activity of analogues of YM022. Novel (3-amino substituted phenyl)urea derivatives of 1,4-benzodiazepin-2-one as gastrin/cholecystokinin-B receptor antagonists

A series of (3-substituted phenyl)urea analogues of the potent gastrin/cholecystokinin (CCK)-B receptor antagonist YM022 has been prepared. Structure activity relationship studies of this series suggested that a number of analogues retained good in vitro potency for gastrin/CCK-B receptor. In particular, the (3-amino substituted phenyl)urea derivatives (10-12) were more potent inhibitors of pentagastrin-induced gastric acid secretion in rats than YM022 on intraduodenal (i.d.) administration.

Tyrosine kinase inhibitors. 4. Structure-activity relationships among N- and 3-substituted 2,2'-dithiobis(1H-indoles) for in vitro inhibition of receptor and nonreceptor protein tyrosine kinases

A series of 3-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC50s 1-20 μM), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N- thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC50s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol- containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.