1943-67-5

Usage

Uses

Used in Pharmaceutical Industry:
4-TERT-BUTYLPHENYL ISOCYANATE is used as a key intermediate in the synthesis of N-(4-tert-butylphenyl)-5-[(4-fluorophenyl)sulfamoyl]-1,3-dihydro-2H-isoindole-2-carboxamide, a compound with potential pharmaceutical applications. Its unique structure and reactivity make it a valuable component in the development of new drugs and therapeutic agents.

InChI:InChI=1/C11H13NO/c1-11(2,3)9-4-6-10(7-5-9)12-8-13/h4-7H,1-3H3

Upstream product

• 116-16-5 1,1,1,3,3,3-hexachloro-propan-2-one 
• 769-92-6 4-tert-Butylaniline 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 530-62-1 1,1'-carbonyldiimidazole 
• 63429-97-0 N-(4-(tert-butyl)phenyl)formamide 
• 201230-82-2 carbon monoxide 
• 3282-56-2 4-tert-butylnitrobenzene 

Downstream Products

• 393514-24-4 N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide 
• 154871-12-2 methyl 4-[3-(4-tert-butylphenyl)-2-oxo-5-oxazolidinyl]methoxybenzoate 
• 675601-79-3 1-(4-t-butylphenyl)-3-((R)-1-isoquinolin-5-ylpyrrolidin-3-yl)urea, hydrochloride salt 
• 1025958-01-3 methyl {4-[({[(4-tert-butylphenyl)amino]carbonyl}{4-[(4-butylphenyl)ethynyl]benzyl}amino)methyl]phenoxy}acetate 
• 874651-21-5 3-(4-tert-butyl-phenyl)-5,5-dimethyl-1-quinolin-4-ylmethyl-imidazolidine-2,4-dione 

Relevant academic research and scientific papers

Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression

Aurora Kinase B is a serine-threonine kinase known to be overexpressed in several cancers, with no inhibitors approved for clinical use. Herein, we present the discovery and optimization of a series of novel quinazoline-based Aurora Kinase B inhibitors. The lead inhibitor SP-96 shows sub-nanomolar potency in Aurora B enzymatic assays (IC50 = 0.316 ± 0.031 nM). We identified the important pharmacophore features resulting in selectivity against receptor tyrosine kinases. Particularly, SP-96 shows >2000 fold selectivity against FLT3 and KIT which is important for normal hematopoiesis. This could diminish the adverse effect of neutropenia reported in the clinical trials of the Aurora B inhibitor Barasertib, which inhibits FLT3 and KIT in addition to Aurora B. Enzyme kinetics of SP-96 shows non-ATP-competitive inhibition which makes it a first-in-class inhibitor. Further, SP-96 shows selective growth inhibition in NCI60 screening, including inhibition of MDA-MD-468, a Triple Negative Breast Cancer cell line.

Phenylquinoline transient receptor potential vanilloid 1 antagonists for the treatment of pain: Discovery of 1-(2-phenylquinoline-4-carbonyl)-N-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide

Reported herein is the design, synthesis, and pharmacologic characterization of a class of TRPV1 antagonists constructed on a phenylquinoline platform that evolved from Cinchophen lead. This design composes three sections: a phenylquinoline headgroup attached to an aliphatic carboxamides, which is tethered at a phenyl tail group. Optimization of this design led to the identification of 37, comprising a pyrrolidine linker and a trifluoromethyl–phenyl tail. In the TRPV1 functional assay, using cells expressed hTRPV1, 37 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 10.2 nM. In the complete mice analgesic model, 37 exhibited better antinociceptive activity than the positive control BCTC in diverse pain models. All of these results suggested that 37 could be considered as a lead candidate for the further development of antinociceptive drugs.

Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1H-indazole-3-amine as multi-target RTKs inhibitors

VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti-proliferation against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, Tie-2, and EphB4.

Discovery of novel anti-angiogenesis agents. Part 7: Multitarget inhibitors of VEGFR-2, TIE-2 and EphB4

Herein, we embarked on a structural optimization campaign aiming at the discovery of second generation anti-angiogenesis agents with our previously reported BPS-7 as lead compound. A library of 27 compounds has been afforded based on the highly conserved ATP-binding pocket of VEGFR-2, Tie-2, and EphB4. Several title compounds exhibited simultaneous inhibitory effects against three angiogenic RTKs. These compounds with a ‘triplet’ inhibition profile have been identified as novel anti-angiogenic and anticancer agents. The representative VDAU11 displayed prominent anti-angiogenic and anticancer potency and could be considered as a candidate for further optimization. These results indicate that N-(pyridin-2-yl)acrylamide could serve as a novel hinge-binding group of triple inhibitors.

Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents

Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds (7g, 7m, 7o, 8e, 8g, and 8m) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8g exhibited the strongest activity. In particular, compound 8g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure-activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8g may be a potent antitumor agent, representing a promising lead for further optimization.

With anti-tumor effect of a quinazoline-urea derivative and its application (by machine translation)

The present invention relates to a of the general formula (II) anti-tumor function of said quinazoline-urea derivative and its application. The definition of the substituent in the general formula (II) in the specification. This invention, in order to SUO draw non-Buddhist nun and Geftinat compounds as the precursor, retention of SUO draw non-Buddhist nun the pharmocology-carbamido; at the same time, such as in reserved [...] EGFR-TKIs Geftinat, synthesis, and obtain a series of quinazoline-urea derivatives, by the in vitro activity tests, some compounds exhibit excellent anti-tumor activity, such derivatives have high research and utility value. (II). (by machine translation)

Synthesis of unsymmetrical phenylurea derivatives via oxidative cross coupling of aryl formamides with amines under metal-free conditions

A new synthetic approach for phenylurea derivatives involving the cross coupling of N-aryl formamides with amines through the formation of isocyanate intermediates in the presence of hypervalent iodine reagents is described.

Metal free oxidative coupling of aryl formamides with alcohols for the synthesis of carbamates

A direct transformation of N-aryl formamides to the corresponding carbamates via the formation of isocyanate intermediates is achieved in good yields using hypervalent iodine as an oxidant. This journal is

Diazenedicarboxamides as inhibitors of D-alanine: D-alanine ligase (Ddl)

This invention belongs to the field of pharmaceutical chemistry and relates to new diazenedicarboxamides as inhibitors of D-alanine:D-alanine ligaze (Ddl), to procedures for their preparation and pharmaceutical preparations containing the same. Compounds of general formula I: and the pharmaceutically acceptable salts are described. The appropriate substituents are clearly presented in the body of the text and in claims.