83697-81-8

Upstream product

• 608-27-5 2,3-dichloroaniline 
• 532-55-8 Benzoyl isothiocyanate 
• 1147550-11-5 ammonium thiocyanate 
• 98-88-4 benzoyl chloride 
• 65-85-0 benzoic acid 

Downstream Products

• 108107-55-7 C₂₅H₁₆Cl₂N₄O₃S 
• 108107-56-8 C₂₄H₁₃Cl₃N₄O₃S 
• 108107-57-9 C₂₅H₁₆Cl₂N₄O₄S 
• 41542-06-7 1-(2,3-dichlorophenyl)thiourea 

Relevant academic research and scientific papers

Discovery of 6-[(3 S,4 S)-4-Amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methyl-3,4-dihydropyrimidin-4-one (IACS-15414), a Potent and Orally Bioavailable SHP2 Inhibitor

Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) plays a role in receptor tyrosine kinase (RTK), neurofibromin-1 (NF-1), and Kirsten rat sarcoma virus (KRAS) mutant-driven cancers, as well as in RTK-mediated resistance, making the identification of small-molecule therapeutics that interfere with its function of high interest. Our quest to identify potent, orally bioavailable, and safe SHP2 inhibitors led to the discovery of a promising series of pyrazolopyrimidinones that displayed excellent potency but had a suboptimal in vivo pharmacokinetic (PK) profile. Hypothesis-driven scaffold optimization led us to a series of pyrazolopyrazines with excellent PK properties across species but a narrow human Ether-à-go-go-Related Gene (hERG) window. Subsequent optimization of properties led to the discovery of the pyrimidinone series, in which multiple members possessed excellent potency, optimal in vivo PK across species, and no off-target activities including no hERG liability up to 100 μM. Importantly, compound 30 (IACS-15414) potently suppressed the mitogen-activated protein kinase (MAPK) pathway signaling and tumor growth in RTK-activated and KRASmut xenograft models in vivo.

Synthesis and antitumor evaluation of 5-(benzo[: D] [1,3]dioxol-5-ylmethyl)-4-(tert -butyl)- N -arylthiazol-2-amines

A series of novel N-aryl-5-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(tert-butyl)thiazol-2-amines (C1-C31) were synthesized and evaluated for their antitumor activities against HeLa, A549 and MCF-7 cell lines. Some tested compounds showed potent growth inhibition properties with IC50 values generally below 5 μM against the three human cancer cells lines. Compound C27 showed potent activities against HeLa and A549 cell lines with IC50 values of 2.07 ± 0.88 μM and 3.52 ± 0.49 μM, respectively. Compound C7 (IC50 = 2.06 ± 0.09 μM) was the most active compound against A549 cell line, while compound C16 (IC50 = 2.55 ± 0.34 μM) showed the best inhibitory activity against the MCF-7 cell line. The preliminary mechanism of the inhibitory effect was investigated via further experiments, such as morphological analysis by dual AO/EB staining and Hoechst 33342 staining, and cell apoptosis and cycle assessment by FACS analysis. The results illustrated that compound C27 could induce apoptosis and cause both S-phase and G2/M-phase arrests in HeLa cell line. Therefore, compound C27 could be developed as a potential antitumor agent.

Solution-phase microwave assisted parallel synthesis of N,N′-disubstituted thioureas derived from benzoic acid: Biological evaluation and molecular docking studies

An efficient and facile microwave-assisted solution phase parallel synthesis for a 26-member library of N,N′-disubstituted thiourea analogs were accomplished successfully. The reaction time for synthesis of analogs was drastically reduced from a reported 8-12 h to only 10 min. Compounds were more than 95% pure, as characterized by modern analytical techniques, i.e. 1H & 13C NMR and FT-IR. The solid phase structural analysis has also been performed by single crystal XRD analysis. Synthesized compounds were preliminary screened for their in vitro urease inhibition and antifungal activity. Most of the compounds were found to be potent inhibitors of urease. However, the most significant activity was found for 11 with IC 50 of 1.67 μM. The docking scores correlate with the IC 50 values of inhibitors.

Improved Procedures for the Preparation of Cycloalkyl-, Arylalkyl-, and Arylthioureas

An improved procedure for the preparation of arylthioureas consists of the reaction of benzoyl isothiocyanate with anilines in acetone and debenzoylation of the resultant N-aryl-N'-benzoylthioureas with 5percent aqueous sodium hydroxide.Bicycloalkylthioureas and N-(arylalkyl)thioureas (e.g. 9H-9-fluorenylthiourea) are directly prepared from the corresponding isothiocyanates and ammonia.