698397-76-1

Upstream product

• 4315-07-5 4-(trifluoromethoxy)phenylacetic acid 

Downstream Products

• 898271-42-6 2-[4-(trifluoromethoxy)phenyl]acetamide 
• 929611-83-6 5-phenyl-3-(4-trifluoromethoxybenzyl)-1H-pyrazolo[4,3-c][1,8]naphthyridin-4(5H)-one 
• 929612-05-5 3-(4-trifluoromethoxybenzyl)-5-(3-trifluoromethoxyphenyl)-1H-pyrazolo[4,3-c][1,8]naphthyridin-4(5H)-one 

Relevant academic research and scientific papers

Synthesis and biological evaluation of N-acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors

Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un-sulfated forms and promotes the growth of various hormone-dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid-sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N-acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4-(2-perfluoroundecanoylaminoethyl)-phenyl sulfamate, 5r, demonstrated the greatest inhibitory effect, with an IC50 value of 2.18?μm (IC50 value of 2.13?μm for coumarin-7-O-sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.

ANTIBACTERIAL COMPOUNDS

The present invention relates to the following compounds (I) wherein the integers are as defined in the description, and where the compounds may be useful as medicaments, for instance for use in the treatment of tuberculosis (e.g. in combination).

Preparation method of N-phenylacetyl-2-hydroxymethylpyrrolidine-2-formamide and medicinal application of N-phenylacetyl-2-hydroxymethylpyrrolidine-2-formamide

The invention discloses N-phenylacetyl-2-hydroxymethylpyrrolidine-2-formamide as shown in a general formula (I), a preparation method of the compound, a new application of the compound and a pharmaceutical composition containing the compound in the aspect of inhibiting neuroglial cell inflammation. Wherein R1/R2 is equal to H, F, CF3 or OCF3.

Identification of BR102910 as a selective fibroblast activation protein (FAP) inhibitor

Fibroblast activation protein (FAP) belongs to the family of prolyl-specific serine proteases and displays both exopeptidase and endopeptidase activities. FAP expression is undetectable in most normal adult tissues, but is greatly upregulated in sites of tissue remodeling, which include fibrosis, inflammation and cancer. Due to its restricted expression pattern and dual enzymatic activities, FAP inhibition is investigated as a therapeutic option for several diseases. In the present study, we described the structure–activity relationship of several synthesized compounds against DPPIV and prolyl oligopeptidase (PREP). In particular, BR102910 (compound 24) showed nanomolar potency and high selectivity. Moreover, the in vivo FAP inhibition study of BR102910 (compound 24) using C57BL/6J mice demonstrated exceptional profiles and satisfactory FAP inhibition efficacy. Based on excellent in vitro and in vivo profiles, the potential of BR102910 (compound 24) as a lead candidate for the treatment of type 2 diabetes is considered.

Synthesis and biological evaluation of fluorinated N-benzoyl and N-phenylacetoyl derivatives of 3-(4-aminophenyl)-coumarin-7-O-sulfamate as steroid sulfatase inhibitors

In the present work, we report convenient methods for the synthesis of 3-(4-aminophenyl)-coumarin-7-O-sulfamate derivatives N-acylated with fluorinated analogues of benzoic or phenylacetic acid as steroid sulfatase (STS) inhibitors. The design of these potential STS inhibitors was supported by molecular modeling techniques. Additionally, computational docking methods were used to determine the binding modes of the synthesized inhibitors and to identify potential interactions between inhibitors and amino acid residues located in the active site of STS. The inhibitory effects of the synthesized compounds were tested on STS isolated from human placenta and against estrogen receptor-(ER)-positive MCF-7 and T47D cells, as well as ER-negative MDA-MB-231 and SkBr3 cancer cell lines. In the course of our investigation, compounds 6c and 6j demonstrated the highest inhibitory effect in enzymatic STS assays, both with IC50values of 0.18?μM (the IC50value of coumarin-7-O-sulfamate is 1.38?μM, used as a reference). Compound 6j exhibited the highest potency against the MCF-7 and T47D cell lines (15.9?μM and 8.7?μM, respectively). The GI50values of tamoxifen (used as a reference) were 6.8; 10.6; 15.1; 12.5?μM against MCF-7, T47D, MDA-MB-231 and SkBr3 cancer cell lines, respectively. Despite the slightly lower activity of compounds 1 and 2 (both in enzymatic and cell-based experiments) compared to 6g and 6j, analogues 1 and 2 proved to selectively inhibit the growth of ER- and PR-positive cell lines.

INHIBITORS OF TRYPTOPHAN DIOXYGENASES (IDO1 AND TDO) AND THEIR USE IN THERAPY

Pharmaceutical compositions comprising 3-aminoisoxazolopyridine compounds of the Formula I having IDO1 and/or TDO inhibitory activity are described, where W is CR1, N or N-oxide; X is CR2, N or N-oxide; Y is CR3, N or N-oxide; Z is CR4, N or N-oxide; and

Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies

We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as a clinical candidate.

Synthesis and Biological Evaluation of Fluorinated 3-Phenylcoumarin-7-O-Sulfamate Derivatives as Steroid Sulfatase Inhibitors

In the present work, we report the initial results of our study on a series of 3-phenylcoumarin sulfamate-based compounds containing C-F bonds as novel inhibitors of steroid sulfatase. The new compounds are potent steroid sulfatase inhibitors, possessing more than 10 times higher inhibitory potency than coumarin-7-O-sulfamate. In the course of our investigation, compounds 2b and 2c demonstrated the highest inhibitory effect on the enzymatic steroid sulfatase assay; both had IC50 values of 0.27 μm (the IC50 value of coumarin-7-O-sulfamate is 3.5 μm, used as a reference).

N-ACYLPIPERIDINE ETHER TROPOMYOSIN-RELATED KINASE INHIBITORS

The present invention relates to compounds of Formula (I) described herein and their pharmaceutically acceptable salts, and their use in medicine, in particular as Trk antagonists.

Methods and Compositions for Treatment of Scleritis and Related Disorders

The present teachings relate to the field of anti-inflammatory substances and more particularly to compounds that are useful for the treatment of scleritis, a scleritis symptom, or a scleritis-related disorder. In one aspect, methods of treating scleritis, a scleritis symptom, or a scleritis-related disorder generally include administering to a subject a compound of Formula I: or a pharmaceutically acceptable salt, hydrate or ester thereof, wherein W1, W2, R1, L, X, Y, Z, and n1 are defined as described herein.