92-95-5

Usage

Uses

Used in Chemical Analysis:
4-BIPHENYLYL ISOCYANATE is used as a reagent for the identification of hydroxy compounds, with which it forms crystalline derivatives that exhibit definite melting points. This property makes it valuable in the analysis and characterization of hydroxy-containing compounds in various chemical and research applications.

InChI:InChI=1/C13H9NO/c15-10-14-13-8-6-12(7-9-13)11-4-2-1-3-5-11/h1-9H

Upstream product

• 75-44-5 phosgene 
• 92-67-1 4-phenylalanine 
• 92-92-2 biphenyl-4-carboxylic acid 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 201230-82-2 carbon monoxide 
• 92-93-3 1-phenyl-4-nitrobenzene 
• 2113-61-3 biphenyl-4-ylamine; hydrochloride 
• 16648-54-7 ethyl [1,1′-biphenyl]-4-ylcarbamate 

Downstream Products

• 112551-67-4 N-(4-amino-2-methyl-[6]quinolyl)-N'-biphenyl-4-yl-urea 
• 95745-38-3 1,3-di([1,1'-biphenyl]-4-yl)urea 

Relevant academic research and scientific papers

Staphylococcus aureus rnpa inhibitors: Computational-guided design, synthesis and initial biological evaluation

Antibiotic resistance is spreading worldwide and it has become one of the most important issues in modern medicine. In this context, the bacterial RNA degradation and processing machinery are essential processes for bacterial viability that may be exploited for antimicrobial therapy. In Staphylococcus aureus, RnpA has been hypothesized to be one of the main players in these mech-anisms. S. aureus RnpA is able to modulate mRNA degradation and complex with a ribozyme (rnpB), facilitating ptRNA maturation. Corresponding small molecule screening campaigns have recently identified a few classes of RnpA inhibitors, and their structure activity relationship (SAR) has only been partially explored. Accordingly, in the present work, using computational modeling of S. aureus RnpA we identified putative crucial interactions of known RnpA inhibitors, and we used this information to design, synthesize, and biologically assess new potential RnpA inhibitors. The present results may be beneficial for the overall knowledge about RnpA inhibitors belonging to both RNPA2000-like thiosemicarbazides and JC-like piperidine carboxamides molecular classes. We evaluated the importance of the different key moieties, such as the dichlorophenyl and the piperidine of JC2, and the semithiocarbazide, the furan, and the i-propylphenyl ring of RNPA2000. Our efforts could provide a foundation for further computational-guided investigations.

Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity

HDAC8 has been established as one of the vital targets as far as the cancer is concerned. Different compounds having potential HDAC inhibitory activity have been approved by USFDA. However, none of these compounds are selective towards specific HDAC isoform. In this current study, some new hydroxamate derivatives with alkylpiperidine and alkylpiperazine linker moieties have been designed, synthesized and biologically evaluated. All these compounds are effective HDAC8 inhibitors comprising more or less similar cytotoxic potential against different cancer cell lines. It is observed that the piperazine scaffold containing compound is more active than the compound with piperidine scaffold for exerting HDAC8 inhibitory activity. Moreover, the 4-quinolyl cap group is better than the biphenyl group which is better than the benzyl group for producing higher HDAC8 inhibition as well as cytotoxicity. These compounds displayed selective HDAC8 inhibition over HDAC3. Moreover, these compounds showed an increased caspase3/7 activity suggesting their anticancer potential through modulation of apoptotic pathways. Molecular docking study with three potent compounds was performed with both HDAC3 and HDAC8 enzymes to understand the selectivity profile of these compounds. Compound containing 4-quinolyl cap group with alkyl piperazinyl urea linker moiety has been emerged out as the lead molecule that may be further modified to design more effective and selective HDAC8 inhibitors in future.

Development of synthetic aminopeptidase N/CD13 inhibitors to overcome cancer metastasis and angiogenesis

Cancer metastasis is a major barrier to its treatment and an important cause of patient death. Antimetastatic agents hold promise for patients with advanced metastatic tumors. Aminopeptidase N/CD13 (APN) is being pursued by many as an important target against cancer metastasis and angiogenesis, but there are few reports on the in vivo evaluation of synthetic APN inhibitors. Herein, a series of compounds targeting APN were synthesized and evaluated for their antimetastasis and antiangiogenesis potency both in vitro and in vivo. Excitingly, compounds 4m, 4t, and 4cc, with the most potent APN inhibitory activities, displayed significant antimetastasis and antiangiogenesis effects in vitro and in vivo, suggesting that those synthetic APN inhibitors have the potential to overcome cancer metastasis and angiogenesis.

Postpolymerization modification of hydroxyl-functionalized polymers with isocyanates

The postpolymerization functionalization of hydroxyl-group terminated polymers (Mn in the range of 1000-6000 g mol-1) such as poly(ethylene glycol) (PEG), poly(N-isopropylacrylamide) (PNIPAM), poly(N,N-dimethylacrylamide) (PDMAM), and poly(tert-butyl acrylate) (PtBA) with a wide range of functional isocyanate derivatives such as azobenzene, viologen, and anthracene has been investigated. It was shown by 1H and 13C NMR, GPC, Fourier transform infrared spectroscopy (FTIR), and electrospray ionization mass spectrometry (ESI-MS) that a high degree of end-group conversion, typically >98%, with little or no formation of side products can be achieved at ambient temperature. PNIPAM, PDMAM, PtBA, and PHEAM polymers have been obtained by reversible addition-fragmentation chain transfer (RAFT) radical polymerization from a hydroxyl-group containing chain transfer agent (CTA). The formation of the carbamate has been shown to be compatible with the trithiocarbonate end-group of the RAFT polymers. Additionally, this approach allows for the direct functionalization of RAFT polymers without the need of additional steps such as deprotection or aminolysis of the CTA. This route was subsequently used for the preparation of a variety of side-chain functional polymers from poly(N-hydroxyethyl acrylamide) (PHEAM). Three different high yielding methods have been employed to prepare the isocyanates (R-NCO). Either amino or carboxylic acid precursors have been converted into the desired R-NCO or hydroxyl group moieties have been reacted with an excess of 1,6-hexamethylene diisocyanate (HDI) to statistically form the monofunctional product.

Anti-cancer activity of T-type calcium channel blocker in vivo

3,4-Dihydroquinazoline 1 as T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/c-nu Slc mice, which exhibited 54% tumor growth inhibition through oral administration of 8 mg/kg of body weight and was slightly less active than doxorubicin (68%). In addition, this compound was also profiled for its acute toxicity to ICR mice to afford oral LD50 value of 1,038 mg/kg of body weight.

Antitumor activity of 3,4-dihydroquinazoline dihydrochloride in A549 xenograft nude mice

In the previous article we have reported that 3,4-dihydroquinazoline 1 is a potent and selective T-type calcium channel blocker that exhibited strong anti-cancer activity in vitro. Compound 1·2HCl was further in vivo evaluated against A549 xenograft in BALB/c nude mice, which exhibited 49% tumor-weight inhibition through intravenous administration of 2 mg/kg of body weight and was more potent than doxorubicin. Moreover, compound 1·2HCl has an oral bioavailability of 98% with LD50 values of 693 mg/kg (po route) and 40.0 mg/kg (iv route) of body weight. In addition, its efficient scale-up synthetic method was developed.

Structure-based design, synthesis, and characterization of inhibitors of human and Plasmodium falciparum dihydroorotate dehydrogenases

Pyrimidine biosynthesis is an attractive drug target in a variety of organisms, including humans and the malaria parasite Plasmodium falciparum. Dihydroorotate dehydrogenase, an enzyme catalyzing the only redox reaction of the pyrimidine biosynthesis pathway, is a well-characterized target for chemotherapeutical intervention. In this study, we have applied SPROUT-LeadOpt, a software package for structure-based drug discovery and lead optimization, to improve the binding of the active metabolite of the anti-inflammatory drug leflunomide to the target cavities of the P. falciparum and human dihydroorotate dehydrogenases. Following synthesis of a library of compounds based upon the SPROUT-optimized molecular scaffolds, a series of inhibitors generally showing good inhibitory activity was obtained, in keeping with the SPROUTLeadOpt predictions. Furthermore, cocrystal structures of five of these SPROUT-designed inhibitors bound in the ubiquinone binding cavity of the human dihydroorotate dehydrogenase are also analyzed.

Novel potent and efficacious nonpeptidic urotensin II receptor agonists

Six different series of nonpeptidic urotensin II receptor agonists have been synthesized and evaluated for their agonistic activity in a cell-based assay (R-SAT). The compounds are ring-opened analogues of the isochromanone-based agonist AC-7954 with different functionalities constituting the linker between the two aromatic ring moieties. Several of the compounds are highly potent and efficacious, with N-[1-(4-chlorophenyl)-3-(dimethylamino)- propyl]-4-phenylbenzamide oxalate (5d) being the most potent. The pure enantiomers of 5d were obtained from the corresponding diastereomeric amides. It was shown by a combination of X-ray crystallography and chemical correlation that the activity resides in the S-enantiomer of 5d (pEC50 7.49).

Selective muscarinic antagonists. II. Synthesis and antimuscarinic properties of biphenylylcarbamate derivatives

A novel series of biphenylylcarbamate derivatives were synthesized and evaluated for binding to M1, M2 and M3 receptors and for antimuscarinic activities. Receptor binding assays indicated that biphenyl-2-ylcarbamate derivatives had high affinities for M1 and M3 receptors and good selectivities for M3 receptor over M2 receptor, indicating that the biphenyl-2-yl group is a novel hydrophobic replacement for the benzhydryl group in the muscarinic antagonist field. In this series, quinuclidin-4-yl biphenyl-2-ylcarbamate monohydrochloride (81, YM-46303) exhibited the highest affinities for M1 and M3 receptors, and selectivity for M3 over M2 receptor. Compared to oxybutynin, YM-46303 showed approximately ten times higher inhibitory activity on bladder pressure in reflexly-evoked rhythmic contraction, and about 5-fold greater selectivity for urinary bladder contraction against salivary secretion in rats. Moreover, selective antagonistic activity was also observed in vitro. Further evaluation of antimuscarinic effects on bradycardia and pressor in pithed rats, and on tremor in mice, showed that YM-46303 can be useful for the treatment of urinary urge incontinence as a bladder-selective M3 antagonist with potent activities and fewer side effects.