877057-25-5

Upstream product

• 111119-36-9 (S)-2-amino-3-(2,4-dichlorophenyl)propanoic acid 
• 114873-04-0 (S)-2-(tert-butoxycarbonylamino)-3-(2,4-dichlorophenyl)propanoic acid 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 877057-26-6 (S)-tert-butyl-1-azido-3-(2,4-dichlorophenyl)propan-2-yl-carbamate 
• 1357194-46-7 (S)-1-azido-3-(2,4-dichlorophenyl)propan-2-amine hydrochloride 

Relevant academic research and scientific papers

Structure-guided discovery of selective methionyl-tRNA synthetase inhibitors with potent activity against: Trypanosoma brucei

Based on crystal structures of Trypanosoma brucei methionyl-tRNA synthetase (TbMetRS) bound to inhibitors, we designed, synthesized, and evaluated two series of novel TbMetRS inhibitors targeting this parasite enzyme. One series has a 1,3-dihydro-imidazol-2-one containing linker, the other has a rigid fused aromatic ring in the linker. For both series of compounds, potent inhibition of parasite growth was achieved with EC50 20?000 nM. Selectivity over human mitochondrial methionyl tRNA synthetase was also evaluated, using a cell-based mitochondrial protein synthesis assay, and selectivity in a range of 20-200-fold was achieved. The inhibitors exhibited poor permeability across the blood brain barrier, necessitating future efforts to optimize the compounds for use in late stage human African trypanosomiasis.

5 - thiazole amides and biological applications

The invention relates to a 5-thiazole amide compound and biology application thereof. The 5-thiazole amide compound has a general formula (I) described in the specification and is used for targeting an AKT/PKB kinase (ATP binding site). Experiments prove that a thiazole amide AKT inhibitor can remarkably inhibit the activity of the AKT kinase in vitro and has strong proliferation inhibition function on various tumor cells with high AKT activity, which indicate that the 5-thiazole amide compound can be used for preparing drugs for resisting tumors.

SPECIFIC INHIBITORS OF METHIONYL-TRNA SYNTHETASE

The present disclosure is generally directed to compositions useful in the inhibition of MetRS and methods for treating diseases that are ameliorated by the inhibition of MetRS.

New thiazole carboxamides as potent inhibitors of Akt kinases

A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)- 2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC50 values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3β proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents.

INHIBITORS OF AKT ACTIVITY

Invented are novel substituted pyridine compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

5H-CYCLOPENTA[D]PYRIMIDINES AS AKT PROTEIN KINASE INHIBITORS

Compounds of Formula I are useful for inhibiting AKT protein kinases. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed. Formula (I).

Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith

Provided herein are Heterocyclic Compounds having the following structure: wherein R1, R2, X, Y and Z are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heterocyclic Compound to a patient in need thereof.