694499-30-4

Upstream product

• 630125-84-7 N-(4-bromomethyl-3-trifluoromethylphenyl)-2,2,2-trifluoroacetamide 
• 393-06-6 4-amino-2-(trifluoromethyl)benzoic acid 
• 1408000-40-7 tert-butyl N-[4-(bromomethyl)-3-(trifluoromethyl)phenyl]carbamate 
• 1408000-39-4 tert-butyl N-[4-methyl-3-(trifluoromethyl)phenyl]carbamate 
• 65934-74-9 3-(trifluoromethyl)-4-methylaniline 
• 919278-28-7 (4-amino-2-(trifluoromethyl)phenyl)(morpholino)methanone 
• 694499-28-0 4-(4-nitro-2-trifluoromethyl-benzyl)-morpholine 

Downstream Products

• 1232836-32-6 C₂₀H₂₀F₃IN₂O₂ 
• 1408000-45-2 3-azido-4-methyl-N-(4-(morpholinomethyl)-3-(trifluoromethyl)phenyl)benzamide 
• 1408000-05-4 C₂₈H₂₅F₃N₈O₂ 
• 1086423-48-4 3-amino-4-methyl-N-(4-(morpholinomethyl)-3-(trifluoromethyl) phenyl)benzamide 

Relevant academic research and scientific papers

ISOQUINOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF DISEASES

The present invention discloses compounds according to Formula (I) wherein R1, R2, R3, L1, L2, and L3 are as defined herein. The present invention relates to compounds inhibiting discoidin domain receptors (DDRs), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases by administering a compound of the invention.

6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS

The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.

Substituted diaryl amide compound as well as preparation method and application thereof

The invention provides a substituted diaryl amide compound as well as a preparation method and application thereof. The substituted diaryl amide compound or a pharmaceutically acceptable salt thereofis of a structure of a formula [1] (the formula is shown

Discovery of Novel Potent VEGFR-2 Inhibitors Exerting Significant Antiproliferative Activity against Cancer Cell Lines

Computational and experimental studies were applied to the discovery of a series of novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors. Eight compounds exhibited nanomolar IC50 values against VEGFR-2, and compounds 6, 19,

NOVEL INHIBITORS OF MAP4K1

The invention relates to novel inhibitors of MAP4K1 (HPK1) useful for the treatment of diseases or disorders characterised by dysregulation of the signal transduction pathways associated with MAPK activation, including hyperproliferative diseases, diseases of immune system dysfunction, inflammatory disorders, neurological diseases, and cardiovascular diseases. The invention further relates to pharmaceutical compositions comprising the same and methods of treatment of said diseases and disorders. The inhibitors are of formula (I) wherein the definitions for A, D, E, F, R5, R6, R7, Z, ring Q, n, x and y are as given in the application.

Design, synthesis and evaluation of derivatives based on pyrimidine scaffold as potent Pan-Raf inhibitors to overcome resistance

Simutaneous targeting all Raf isoforms offers the prospect of enhanced efficacy as well as reduced potential for resistance. Described herein is the discovery and characterization of a series of pyrimidine scaffold with DFG-out conformation as potent Pan-Raf inhibitors. Among them, I-41 with excellent Pan-Raf potency demonstrates inhibitory activity against BRafWTphenotypic melanoma and BRafV600Ephenotypic colon cells. The western blot results for the Erk inhibition in human melanoma SK-Mel-2?cell lines showed I-41 inhibited the proliferation of SK-Mel-2?cell lines without paradoxical activation of Erk, which supported I-41 may become a good candidate compound to overcome the resistance of melanoma against the current BRafV600Einhibitor therapy. I-41 also have a favorable pharmacokinetic profile in rat. Synthesis, SAR, lead selection, and evaluation of the key compounds studies are described.

Rational design, synthesis, and biological evaluation of Pan-Raf inhibitors to overcome resistance

Selective BRafV600E inhibitors with DFG-in conformation have been proven effective against a subset of melanoma. However, representative inhibitor vemurafenib rapidly acquires resistance in the BRafWT cells through a CRaf or BRafWT dependent manner. Simultaneous targeting of all subtypes of Raf proteins offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Herein, we describe the design and characterization of a series of compounds I-01-I-22, based on a pyrimidine scaffold with DFG-out conformation as Pan-Raf inhibitors. Among them, I-15 binds to all Raf protomers with IC50 values of 12.6 nM (BRafV600E), 30.1 nM (ARaf), 19.7 nM (BRafWT) and 17.5 nM (CRaf) and demonstrates cellular activity against BRafWT phenotypic melanoma and BRafV600E phenotypic colorectal cancer cells. The western blot results for the P-Erk inhibition in human melanoma SK-Mel-2 cell line showed that I-15 inhibited the proliferation of the SK-Mel-2 cell line at concentrations as low as 400 nM, without paradoxical activation of Erk as vemurafenib, which supported that I-15 may become a good candidate compound to overcome the resistance of melanoma induced by vemurafenib. I-15 also has a favorable pharmacokinetic profile in rats. Rational design, synthesis, SAR, lead selection and evaluation of the key compounds studied are described.

Potent Pan-Raf and Receptor Tyrosine Kinase Inhibitors Based on a Cyclopropyl Formamide Fragment Overcome Resistance

While selective BRafV600E inhibitors have been proven effective clinically, acquired resistance rapidly develops through reactivation of the mitogen-activated protein kinase (MAPK) pathway. Simultaneous targeting of multiple nodes in the pathway offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Replacement pyridine group of Y-1 by a cyclopropyl formamide group afforded I-01 as a novel multitargeted kinase inhibitor template. I-01 displayed enzyme potency against Pan-Raf and receptor tyrosine kinases (RTKs). Based on the binding mode of I-01, analogues I-02-I-18 were designed and synthesized. The most promising compound I-16 potently inhibits all subtypes of Rafs with IC50 values of 3.49 (BRafV600E), 8.86 (ARaf), 5.78 (BRafWT), and 1.65 nM (CRaf), respectively. I-16 not only exhibit comparable antiproliferative activities with positive control compounds against HepG2, SW579, MV4-11, and COLO205 cell lines, but also suppress the proliferation of melanoma SK-MEL-2 harboring overexpressed BRafWT with IC50 values of 0.93 μM. The Western blot results for the ERK inhibition in human melanoma SK-MEL-2 cell lines show that I-16 inhibits the proliferation of SK-MEL-2 cell lines without paradoxical activation of ERK, which support the hypothesis that the inhibition of Pan-Raf and RTKs might be a tractable strategy to overcome the resistance of melanoma induced by the therapy with the current selective BRafV600E inhibitors.

Discovery of a Nanomolar Multikinase Inhibitor (KST016366): A New Benzothiazole Derivative with Remarkable Broad-Spectrum Antiproliferative Activity

Herein we report the discovery of compound 6 [KST016366; 4-((2-(3-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)ureido)benzo[d]thiazol-6-yl)oxy)picolinamide] as a new potent multikinase inhibitor through minor structural modification of our

Design and Development of a Series of Potent and Selective Type II Inhibitors of CDK8

Using Sorafenib as a starting point, a series of potent and selective inhibitors of CDK8 was developed. When cocrystallized with CDK8 and cyclin C, these compounds exhibit a Type-II (DMG-out) binding mode.