7366-56-5

Usage

Chemical Properties

White powder

InChI:InChI=1/C8H8N2O2S/c9-8(13)10-6-3-1-5(2-4-6)7(11)12/h1-4H,(H,11,12)(H3,9,10,13)/p-1

Upstream product

• 1147550-11-5 ammonium thiocyanate 
• 22669-27-8 p-aminobenzoic acid hydrochloride 
• 150-13-0 4-amino-benzoic acid 
• 532-55-8 Benzoyl isothiocyanate 
• 2131-62-6 4-isothiocyanatobenzoic acid 
• 40611-30-1 4-(3-benzoylthioureido)benzoic acid 

Downstream Products

• 100142-85-6 4-(4,5-dimethyl-thiazol-2-ylamino)-benzoic acid 
• 31102-83-7 4-(2-imino-thiazolo[4,5-b]quinoxalin-3-yl)-benzoic acid 
• 31102-70-2 4-thiazolo[4,5-b]quinoxalin-2-ylamino-benzoic acid 
• 82844-30-2 4-[4,4-Bis-(2-hydroxy-phenyl)-5-oxo-2-thioxo-imidazolidin-1-yl]-benzoic acid 
• 116433-32-0 C₃₂H₂₈N₆O₈S₃ 
• 82844-42-6 4-[4,4-Bis-(4-hydroxy-phenyl)-5-oxo-2-thioxo-imidazolidin-1-yl]-benzoic acid 
• 37182-78-8 4-(4-phenylthiazol-2-ylamino) benzoic acid 
• 255833-41-1 4-((5-phenyl-4-(trifluoromethyl)thiazol-2-yl)amino)benzoic acid 
• 738523-12-1 4-(3-methylguanidino)benzoic acid 
• 698969-65-2 4-(3,3-dimethylguanidino)benzoic acid 

Relevant academic research and scientific papers

5,8-DISUBSTITUTED-[1,2,4]TRIAZOLO[1,5-A]PYRIDINYL AND 5,8-DISUBSTITUTED-IMIDAZO[1,2-A]PYRIDINE DERIVATIVES USEFUL AS INHIBITORS OF ENTEROPEPTIDASE

The present invention is directed to 5,8-disubstituted-[1,2,4]triazolo[1,5- a]pyridinyl and 5,8-disubstituted-imidazo[1,2-a]pyridine derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by the enteropeptidase enzyme.

2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 2. Structure-Based Optimization and Investigation of Effects Specific to the Allosteric Mode of Action

Protein CK2 has gained much interest as an anticancer drug target in the past decade. We had previously described the identification of a new allosteric site on the catalytic α-subunit, along with first small molecule ligands based on the 4-(4-phenylthiazol-2-ylamino)benzoic acid scaffold. In the present work, structure optimizations guided by a binding model led to the identification of the lead compound 2-hydroxy-4-((4-(naphthalen-2-yl)thiazol-2-yl)amino)benzoic acid (27), showing a submicromolar potency against purified CK2α (IC50 = 0.6 μM). Furthermore, 27 induced apoptosis and cell death in 786-O renal cell carcinoma cells (EC50 = 5 μM) and inhibited STAT3 activation even more potently than the ATP-competitive drug candidate CX-4945 (EC50 of 1.6 μM vs 5.3 μM). Notably, the potencies of our allosteric ligands to inhibit CK2 varied depending on the individual substrate. Altogether, the novel allosteric pocket was proved a druggable site, offering an excellent perspective to develop efficient and selective allosteric CK2 inhibitors.

2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 1. Identification of an Allosteric Binding Site

CK2 is a ubiquitous Ser/Thr protein kinase involved in the control of various signaling pathways and is known to be constitutively active. In the present study, we identified aryl 2-aminothiazoles as a novel class of CK2 inhibitors, which displayed a non-ATP-competitive mode of action and stabilized an inactive conformation of CK2 in solution. Enzyme kinetics studies, STD NMR, circular dichroism spectroscopy, and native mass spectrometry experiments demonstrated that the compounds bind in an allosteric pocket outside the ATP-binding site. Our data, combined with molecular docking studies, strongly suggested that this new binding site was located at the interface between the αC helix and the flexible glycine-rich loop. A first hit optimization led to compound 7, exhibiting an IC50 of 3.4 μM against purified CK2α in combination with a favorable selectivity profile. Thus, we identified a novel class of CK2 inhibitors targeting an allosteric pocket, offering great potential for further optimization into anticancer drugs.

Facile synthesis of some condensed 1,3-thiazines and thiazoles under conventional conditions: antitumor activity

1,3-Thiazine 3 was obtained from cinnamoyl thiourea derivative 2 as the kinetic control product. Refluxing of 2 with sodium ethoxide afforded pyrimidine derivative 4. Moreover, stirring of 2 with bromine/acetic acid gave thiazole 5 that was condensed with o-phenylene diamine forming benzimidazole 6. Heating of arylthiourea 8 with maleic anhydride or phenacyl chloride afforded thiazole derivatives 9 and 10, respectively. Condensation of compound 10 with o-phenylene diamine gave benzimidazole 11. Reaction of p-amino benzoic acid with chloro acetyl isothiocyanate, acetylacetone and ethylacetoacetate produced imidazole 14, enaminone 15 and crotonate 16 derivatives, respectively. Stirring a mixture of benzoyl isothiocyanate with 15 and/or 16 resulted in pyridine-2-thione 17. The yields of the prepared compounds were 41–93%. The experimental section is simple and easy. The detailed synthesis, spectroscopic data, IC50 and antitumor activity of the synthesized compounds were reported. The cytotoxicity of the newly synthesized products showed that compound 4 is the most active compound towards the cancer cell line at which its reactivity is higher than that of the standard doxorubicin (anticancer reference drug).

Synthesis and in-vitro evaluation of 2-amino-4-arylthiazole as inhibitor of 3D polymerase against foot-and-mouth disease (FMD)

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease of livestock caused by a highly variable RNA virus, foot-and-mouth disease virus (FMDV). One of the targets to suppress expansion of and to control FMD is 3D polymerase (FMDV 3Dpol). In this study, 2-amino-4-arylthiazole derivatives were synthesized and evaluated for their inhibitory activity against FMDV 3Dpol. Among them, compound 20i exhibited the most potent functional inhibition (IC50 = 0.39μM) of FMDV 3D polymerase and compound 24a (EC50=13.09 μM) showed more potent antiviral activity than ribavirin (EC50=1367 μM) and T1105 (EC50=347 μM) with IBRS-2 cells infected by the FMDV O/SKR/2010 strain.

Inhibitory effect of 4-aryl 2-substituted aniline-thiazole analogs on growth of human prostate cancer LNCap cells

Androgen receptor (AR) is ligand-inducible nuclear hormone receptor which has been focused on key molecular target in growth and progression of prostate cancer. We synthesized a series of 4-aryl 2-substituted aniline-thiazole analogs and evaluated their anti-cancer activity in AR-dependent human prostate cancer LNCap cells. Among them, the compound 6 inhibited the tumor growth in LNCap-inoculated xenograft model.

Synthesis and antibacterial activity of isochromene and isoquinoline derivative

Synthesis of 4-thioureidobenzoic acid (2), which on cyclization with ethyl chloroacetate gave 4-(2-imino-5-oxothiazolidin-3-yl)-benzoic acid (3), which on further reacting with benzoin (4) in the presence of polyphosphoric acid afforded the synthesis of 2-imino-3-(-1-oxo-3,4-diphenyl-1H-isochromen-6-yl) thiazolidin-5-one (5). Compound 5 was then reacted with substituted anilines to give 6-(2-imino-5-oxothiazolidin-3-yl)-3,4-diphenyl-2-(substituted)-isoquinolin- 1(2H)-one (6). The structures of the compounds have been elucidated on the basis of IR 1HNMR, 13C NMR, and elemental analysis. Representative samples were screened for their antimicrobial activity against gram-negative bacteria, E. coli and P. aeruginosa and gram-positive bacteria, S. aureus, and C. diphtheriae using disc diffusion method.

Design, synthesis and pharmacological screening of hybrid molecules as antihypertensives

The synthesis and pharmacological profile of a series of hybrid compounds bearing the dihydropyrimidine moiety and substituted phenylthioureas joined via typical b-blocker aryloxypropanolamine group are described. Seven out of 10 new compounds tested proved to be endowed with negative inotropic and chronotropic effect as compared to Adrenaline on isolated perfused frog heart. Also ECG studies that were carried out on normotensive male rats showed that the most of the compounds exhibited significant reduction in Rmax value in the first 30 min although maintaining little change in heart rate, with hypotensive effect lasting for 1 h.We concluded that the most of the synthesized novel compounds exhibited hypotensive as well as antihypertensive effects which could be attributed to blockade of Ca2+ entry and β-adrenoreceptor blocking activities due to introduction of aryloxypropanolamine linked to N-1 substituted dihydropyrimidine moiety. Brady cardiac effects of compounds 5a-5d, 6c-6e resulting from Ca2+entry and β-adrenoreceptor blocking attenuate the sympathetic activation-associated reflex tachycardia in the heart. We selected compound 5c as a promising lead for further detailed pharmacological and preclinical evaluation studies. Springer Science+Business Media, LLC 2010.

Substituted N-phenylisothioureas: Potent inhibitors of human nitric oxide synthase with neuronal isoform selectivity

S-Ethyl N-phenylisothiourea (4) has been found to be a potent inhibitor of both the human constitutive and inducible isoforms of nitric oxide synthase. A series of substituted N-phenylisothiourea analogues was synthesized to investigate the structure-activity relationship of this class of inhibitor. Each analogue was evaluated for human isoform selectivity. One analogue, S-ethyl N-[4-(trifluoromethyl)phenyl]isothiourea (39), exhibited 115-fold and 29-fold selectivity for the neuronal isoform versus the inducible and endothelial derived constitutive isoforms, respectively. Studies have shown the substituted N-phenylisothiourea 39 binds competitively with L,-arginine.

Synthesis and structure-activity study of protease inhibitors. V. Chemical modification of 6-amidino-2-naphthyl 4-guanidinobenzoate

By developing 6-amidino-2-naphthyl 4-guanidinobenzoate (I, FUT-175) as a basic structure, its various derivatives were synthesized and their inhibitory activities on trypsin, plasmin, kallikrein, thrombin, C1r and C1s as well as on complement-mediated hemolysis were examined. The protective effect of these compounds on complement-mediated Forssman shock was also examined in guinea pigs. 6-Amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate (41, FUT-187) was found to be a suitable compound for oral administration with anti-complement activity superior to that of compound I.