34667-88-4

Usage

Chemical Properties

Light yellow solid

Upstream product

• 4110-33-2 2,4-dinitrobenzonitrile 
• 350-32-3 2-fluoro-4-nitrobenzamide 
• 108-86-1 bromobenzene 
• 584-48-5 2,4-dinitrobromobenzene 
• 403-24-7 2-fluoro-4-nitrobenzoic acid 
• 1427-07-2 2-fluoro-4-nitrotoluene 
• 403-23-6 2-fluoro-4-nitrobenzoyl chloride 

Downstream Products

• 35212-90-9 methyl 3-amino-6-nitro<1>benzothiophene-2-carboxylate 
• 900174-91-6 C₇H₉FN₂ 
• 526218-63-3 2-(6-bromo-2-naphthyloxy)-4-nitrobenzonitrile 
• 89793-83-9 6-nitrobenzo[d]isoxazol-3-amine 
• 1430217-63-2 (S)-(9H-fluoren-9-yl)methyl 1-(4-cyano-3-fluorophenylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1430216-43-5 (S,E)-N-(3-amino-1H-indazol-6-yl)-2-(3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acryloyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide trifluoroacetate 
• 836611-13-3 4-nitro-2-(phenylthio)benzonitrile 
• 147696-60-4 4-Cyano-3-phenylthiobenzenamine 
• 1333950-28-9 C₂₂H₁₇N₇O 
• 1333950-27-8 C₂₃H₁₈N₆O₂ 
• 1333950-26-7 C₂₁H₁₆N₆O₃ 
• 1333950-25-6 C₂₀H₁₆N₄S 
• 1333950-24-5 C₁₉H₁₆N₄OS 
• 1333950-23-4 C₁₈H₁₃ClN₄OS 

Relevant academic research and scientific papers

Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents

Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists.

Thrombin or factor Xa inhibitors

This invention relates generally to inhibitors of trypsin-like serine protease enzymes, especially factor Xa or thrombin, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.

Irreversible inhibitors of tyrosine kinases

The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.

Exploiting subsite S1 of trypsin-like serine proteases for selectivity: Potent and selective inhibitors of urokinase-type plasminogen activator

A nonselective inhibitor of trypsin-like serine proteases, 2-(2-hydroxybiphenyl-3-yl)-lH-indole-5-carboxamidine (1) (Verner, E.; Katz, B. A.; Spencer, J.; Allen, D.; Hataye, J.; Hruzewicz, W.; Hui, H. C.; Kolesnikov, A.; Li, Y.; Luong, C.; Martelli, A.; Radika. K.; Rai, R.; She, M.; Shrader, W.; Sprengeler, P. A.; Trapp, S.; Wang, J.; Young, W. B.; Mackman, R. L. J. Med. Chem. 2001, 44, 2753-2771) has been optimized through minor structural changes on the S1 binding group to afford remarkably selective and potent inhibitors of urokinase-type plasminogen activator (uPA). The trypsin-like serine proteases1 that comprise drug targets can be broadly categorized into two subfamilies, those with Ser190 and those with Ala190. A single-atom modification, for example, replacement of hydrogen for chlorine at the 6-position of the 5-amidinoindole P1 group on 1, generated up to 6700-fold selectivity toward the Ser190 enzymes and against the Alal90 enzymes. The larger chlorine atom displaces a water molecule (H2O1s1) that binds near residue 190 in all the complexes of 1, and related inhibitors, in uPA, thrombin, and trypsin. The water molecule, H2O1s1, in both the Ser190 or Ala190 enzymes, hydrogen bonds with the amidine N1 nitrogen of the inhibitor. When it is displaced, a reduction in affinity toward the Ala190 enzymes is observed due to the amidine N1 nitrogen of the bound inhibitor being deprived of a key hydrogen-bonding partner. In the Ser190 enzymes the affinity is maintained since the serine hydroxyl oxygen Oγser190 compensates for the displaced water molecule. Highresolution crystallography provided evidence for the displacement of the water molecule and validated the design rationale. In summation, a novel and powerful method for engineering selectivity toward Ser190 proteases and against Ala190 proteases without substantially increasing molecular weight is described.

Synthesis of [1]Benzothieno[3,2-d]pyrimidines Substituted with Electron Donating Substituents on the Benzene Ring

Various 2-fluorobenzonitriles were converted to the corresponding 3-amino[1]benzothiophenecarboxylic acid esters, which in turn were annulated with formamidine or various equivalents to produce the desired tricyclic benzothienopyrimidines. Various methoxy and nitro/amino substituants were placed on the phenyl ring, requiring several different strategies to prepare the desired benzothiophenes. Several different pyrimidone annulations were also required. The use of an electron rich 2-bromobenzonitrile in a four-step one-pot low temperature lithiation sequence to produce highly electron-rich amino[1]benzothiophenecarboxylate esters is also described. The synthesis of 7-amino-8-fluoro[1]benzothieno[3,2-d]pyrimid-4(3H)-one was relatively straightforward, but synthesis of the corresponding 7-amino-8-protio analogue proved to be very difficult, and required several approaches before a successful one was found.

Fluorodenitrations using Tetramethylammonium Fluoride

Tetramethylammonium fluoride activated by azeotropic drying in situ is an efficient reagent for the fluorodenitration of nitroaromatics.

SYNTHESIS AND SOME PROPERTIES OF 3-FLUORO-4-CYANOPHENYL 4 prime -n-ALKYLBENZOATES.

A series of 3-fluoro-4-cyanophenyl 4 prime -n-alkylbenzoates, which show monotropic nematic phases, was prepared and their transition temperatures and melting enthalpies were measured. The 3-fluoro-4-cyanophenyl 4 prime -n-propylbenzoate, 3-chloro-4-cyanophenyl 4 prime -n-propylbenzoate and 4-cyanophenyl 4 prime -n-propylbenzoate were mixed with a nematic mixture (A) of 4-n-alkoxyphenyl 4 prime -n-alkylcyclohexane-1 prime -carboxylates. 3-Fluoro-4-cyanophenyl 4 prime -n-propylbenzoate decreases the N-I transition temperature less, increases the birefringence more, and increases the bulk viscosity less than 3-chloro-4-cyanophenyl 4 prime -n-propylbenzoate, and reduces the threshold voltage to the greatest extent. The dielectric anisotropies of 3-fluoro-4-cyanophenyl 4 prime -n-propylbenzoate and 4-cyanophenyl 4 prime -n-propylbenzoate determined from a series of solutions of the compounds in nematic mixture (A) are 35. 9 and 29. 6, respectively.