330796-48-0

Usage

Uses

Used in Pharmaceutical Industry:
4-(4-METHYL-PIPERAZIN-1-YL)-3-TRIFLUOROMETHYL-PHENYLAMINE is used as a key intermediate in the synthesis of heterocycle-fused pyrimidine derivatives. These derivatives have potential applications in the development of new drugs and therapeutic agents, particularly in the treatment of various diseases and medical conditions.
Used in Chemical Synthesis:
In the field of organic chemistry, 4-(4-METHYL-PIPERAZIN-1-YL)-3-TRIFLUOROMETHYL-PHENYLAMINE serves as a valuable building block for the creation of more complex molecular structures. Its unique combination of functional groups allows for further chemical reactions and modifications, leading to the development of novel compounds with diverse properties and applications.

InChI:InChI=1/C12H16F3N3/c1-17-4-6-18(7-5-17)11-3-2-9(16)8-10(11)12(13,14)15/h2-3,8H,4-7,16H2,1H3

Upstream product

• 109-01-3 1-methyl-piperazine 
• 367-67-9 2-bromo-5-nitro-benzotrifluoride 
• 400-74-8 2-Fluoro-5-nitrobenzotrifluoride 
• 309734-66-5 1-methyl-4-(4-nitro-2-(trifluoromethyl)phenyl)piperazine 

Relevant academic research and scientific papers

NOVEL CONFORMATIONALLY-RESTRICTED ANALOGUES OF SORAFENIB AND REGORAFENIB AS SELECTIVE KINASE INHIBITORS FOR CANCER TREATMENT

Novel conformationally-restricted analogues of sorafenib and regorafenib as selective kinase inhibitors for therapeutic formulations and methods for treating cancer.

QUINAZOLINE-DERIVED HCK INHIBITORS FOR USE IN THE TREATMENT OF MYD88 MUTATED DISEASES

The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be k

Discovery of potent Pan-Raf inhibitors with increased solubility to overcome drug resistance

Despite various applications of kinase inhibitors in oncology and inflammatory diseases, the emergence of resistance still remains the major barrier to achieve long-term remission in cancer treatment. With the aim of overcoming the resistance induced by type IIB BRaf V600E selective inhibitor vemurafenib, and further ameliorating the antiproliferative activity, a novel type IIA Pan-Raf inhibitors Ia–Io based on pyrrolo[2,3-d] pyrimidine scaffold were designed and evaluated in this work. Herein, we tried to improve the cellular potency of the target compounds by increasing their solubility. Among them, Il, with the solubility of 0.107 mg/mL, demonstrated favorable cellular activity against vemurafenib-resistant carcinoma cells including BRafWT phenotypic melanoma SK-MEL-2 and BRafV600E phenotypic colorectal cancer HT-29 cell lines. Based on the well solubility, Il exhibited good metabolic stability compared to sorafenib and showed favorable pharmacokinetic profiles in rats. As for the biological mechanism research, Il had the similar P-ERK kinase inhibitory activity in A375 and SK-Mel-2 cells as our previously lead P-2. Il may become a good candidate compound to overcome the resistance associated with vemurafenib.

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.

FUSED TRICYCLIC UREA COMPOUNDS AS RAF KINASE AND/OR RAF KINASE DIMER INHIBITORS

Provided are certain fused tricyclic urea compounds and salts thereof, compositions thereof, and methods of use therefor.

PROTEIN KINASE C INHIBITORS AND USES THEREOF

This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

PROTEIN KINASE C INHIBITORS AND USES THEREOF

This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

N-(3,4-disubstituted phenyl) salicylamide derivatives

A compound represented by the following formula (I) or a salt thereof: wherein R1, R2, R3 and R4 represent hydrogen atom, a halogen atom, cyano group, nitro group, a C1-4 alkyl group, a halogenated C