51339-40-3

Upstream product

• 6307-83-1 3-bromo-5-nitro-benzoic acid 
• 121-92-6 3-nitrobenzoic acid 
• 618-95-1 methyl 3-nitrobenzoate 
• 6307-87-5 methyl 3-bromo-5-nitrobenzoate 

Downstream Products

• 51339-39-0 (3-bromo-5-nitrophenyl)(phenyl)methanone 
• 51339-36-7 3-Bromo-5-nitro-4'-methoxybenzhydrol 
• 51339-15-2 3-Brom-5-nitro-benzhydrylbromid 
• 51339-29-8 3-Bromo-5-nitrobenzhydrol 
• 51339-21-0 3-Bromo-5-nitro-4'-methoxybenzhydrylbromid 
• 90050-52-5 3-bromo-N-methyl-5-nitrobenzamide 
• 941294-20-8 (3-bromo-5-nitrophenyl)(pyrrolidin-1-yl)methanone 
• 675122-48-2 3-Ethyl-5-(1-methyl-1H-tetrazole-5-yl)aniline 
• 675122-47-1 1-methyl-5-(3-nitro-5-vinylphenyl)-1H-tetraazole 
• 852661-64-4 N-((1R,2S)-3-{cyclohexyl[3-(4-fluorophenyl)propyl]amino}-2-hydroxy-1-methylpropyl)-N'-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]urea 
• 852660-57-2 N-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-N'-((1R,2S)-2-{[((2RS)-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)(methyl)amino]methyl}cyclohexyl)urea 
• 852660-52-7 N-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-N'-((1R,2S)-2-{[((2RS)-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino]methyl}cyclohexyl)urea 
• 852660-89-0 N-{(1R,3R,4S)-4-{[[2,2-dimethyl-3-(4-fluorophenyl)propyl](methyl)amino]methyl}-3-[({[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]amino}carbonyl)amino]cyclohexyl}-N-methylacetamide 
• 675122-49-3 phenyl 3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenylcarbamate 

Relevant academic research and scientific papers

SMALL MOLECULE INHIBITORS OF G PROTEIN COUPLED RECEPTOR 6 KINASE POLYPEPTIDES

This document relates to inhibitors of G protein coupled receptor 6 kinase (GRK6) polypeptides as well as methods and materials for using such inhibitors to treat hematological malignancies, inflammation diseases, and autoimmune disorders.

Discovery of 2-methoxy-3-phenylsulfonamino-5-(quinazolin-6-yl or quinolin-6-yl)benzamides as novel PI3K inhibitors and anticancer agents by bioisostere

2-Substituted-3-sulfonamino-5-(quinazolin-6-yl or quinolin-6-yl)benzamides have been proposed as novel structures of PI3K inhibitors and anticancer agents based on bioisostere. In the present study, 2-substituted-3-sulfonamino-5-(4- morpholinoquinazolin-6-yl)benzamides and 2-methoxy-3-sulfonamino-5-(4- morpholinoquinolin-6-yl)benzamides were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against four human cancer cell lines, including A549, HCT-116, U-87 MG and KB. The SAR of the title compounds was preliminarily discussed. Compound 1a with potent antiproliferative activity was tested for its inhibitory activity against PI3K and mTOR and its effect on the AKT and p-AKT473. The anticancer effect of 1a was evaluated in established nude mice U-87 MG xenograft model. The results suggest that compound 1a can significantly inhibit PI3K/AKT/mTOR pathway and tumor growth. These findings strongly support the assumption that title compounds are potent PI3K inhibitors and anticancer agents.

KINASE INHIBITORS

There are provided compounds of formula I, wherein R1A to R1E, R2 to R5, L and X1 to X3 have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

UREA DERIVATIVES USEFUL AS KINASE INHIBITORS

There are provided compounds of formula I, wherein R1A to R1E, R2 to R5, L and X1 to X3 have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

Design, synthesis and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein

Aberrant activation of oncogenic signal transducer and activator of transcription 3 (STAT3) protein signaling pathways has been extensively implicated in human cancers. Given STAT3's prominent dysregulatory role in malignant transformation and tumorigenesis, there has been a significant effort to discover STAT3-specific inhibitors as chemical probes for defining the aberrant STAT3-mediated molecular events that support the malignant phenotype. To identify novel, STAT3-selective inhibitors suitable for interrogating STAT3 signaling in tumor cells, we explored the design of hybrid molecules by conjugating a known STAT3 inhibitory peptidomimetic, ISS610 to the high-affinity STAT3-binding peptide motif derived from the ILR/gp-130. Several hybrid molecules were examined in in vitro biophysical and biochemical studies for inhibitory potency against STAT3. Lead inhibitor 14aa was shown to strongly bind to STAT3 (KD = 900 nM), disrupt STAT3:phosphopeptide complexes (Ki = 5 μM) and suppress STAT3 activity in in vitro DNA binding activity/electrophoretic mobility shift assay (EMSA). Moreover, lead STAT3 inhibitor 14aa induced a time-dependent inhibition of constitutive STAT3 activation in v-Src transformed mouse fibroblasts (NIH3T3/v-Src), with 80% suppression of constitutively-active STAT3 at 6 h following treatment of NIH3T3/v-Src. However, STAT3 activity recovered at 24 h after treatment of cells, suggesting potential degradation of the compound. Results further showed a suppression of aberrant STAT3 activity in NIH3T3/v-Src by the treatment with compound 14aa-OH, which is the non-pTyr version of compound 14aa. The effect of compounds 14aa and 14aa-OH are accompanied by a moderate loss of cell viability.

Potent mGluR5 antagonists: Pyridyl and thiazolyl-ethynyl-3,5-disubstituted- phenyl series

We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl) ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl) ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity.

FUSED PYRAZINE DERIVATIVES AS KINASE INHIBITORS

A series of quinoxaline derivatives, and analogues thereof, which are functionalised further by a substituted phenyl or pyridinyl moiety, being selective inhibitors of PO kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions.

From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part I: The discovery of CCR3 antagonist development candidate BMS-639623 with picomolar inhibition potency against eosinophil chemotaxis

Conformational analysis of trans-1,2-disubstituted cyclohexane CCR3 antagonist 2 revealed that the cyclohexane linker could be replaced by an acyclic syn-α-methyl-β-hydroxypropyl linker. Synthesis and biological evaluation of mono- and disubstituted propyl linkers support this conformational correlation. It was also found that the α-methyl group to the urea lowered protein binding and that the β-hydroxyl group lowered affinity for CYP2D6. Ab initio calculations show that the α-methyl group governs the spatial orientation of three key functionalities within the molecule. α-Methyl-β-hydroxypropyl urea 31 with a chemotaxis IC50 = 38 pM for eosinophils was chosen to enter clinical development for the treatment of asthma.

PYRIMIDINE DERIVATIVES

The present invention relates to pyrimidine compounds that are useful as agents for the treatment of kinase related disorders such as proliferative disorders. More particularly, the present invention relates to substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of kinase related disorders such as proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.

Substituted fused bicyclic amines as modulators of chemokine receptor activity

The present application describes modulators of CCR3 of formula (Ia) and (Ib): or pharmaceutically acceptable salt forms thereof, wherein Z, R1, R2, R3, R4, R5, R5′, R6, a, b, c, d, and u are as defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using said modulators are disclosed.