1048675-29-1

Upstream product

• 591-31-1 3-methoxy-benzaldehyde 
• 107-15-3 ethylenediamine 

Downstream Products

• 1048675-28-0 2'-Chloro-5'-[5-methanesulfonyl-1-(3-pyrrolidin-1-yl-propyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-biphenyl-3-carboxylic acid [2-(3-methoxy-benzylamino)-ethyl]-amide 
• 1341126-76-8 2-(3-methoxybenzyl)-1,2,5-thiadiazolidine 1,1-dioxide 
• 1415243-27-4 2,7-bis-[2-(3-methoxybenzylamino)ethyl]benzo[lmn][3,8]phenanthroline-1,3,6,8-tetraone 
• 1219729-15-3 C₁₇H₂₀BrN₃O₂ 
• 1571902-18-5 N-(3-methoxybenzyl)benzimidazole 
• 1219722-70-9 3-(4-(1H-pyrazol-4-yl)phenyl)-1-(2-aminoethyl)-1-(3-methoxybenzyl)urea 
• 1350009-61-8 C₂₄H₂₉N₅O₄ 

Relevant academic research and scientific papers

Synthesis and biological evaluation of urea derivatives as highly potent and selective rho kinase inhibitors

RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (～7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.

Structure-activity relationships of novel substituted naphthalene diimides as anticancer agents

Novel 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) derivatives were synthesized and evaluated for their antiproliferative activity on a wide number of different tumor cell lines. The prototypes of the present series were derivatives 1 and 2 characterized by interesting biological profiles as anticancer agents. The present investigation expands on the study of structure-activity relationships of prototypes 1 and 2, namely, the influence of the different substituents of the phenyl rings on the biological activity. Derivatives 3-22, characterized by a different substituent on the aromatic rings and/or a different chain length varying from two to three carbon units, were synthesized and evaluated for their cytostatic and cytotoxic activities. The most interesting compound was 20, characterized by a linker of three methylene units and a 2,3,4-trimethoxy substituent on the two aromatic rings. It displayed antiproliferative activity in the submicromolar range, especially against some different cell lines, the ability to inhibit Taq polymerase and telomerase, to trigger caspase activation by a possible oxidative mechanism, to downregulate ERK 2 protein and to inhibit ERKs phosphorylation, without acting directly on microtubules and tubuline. Its theoretical recognition against duplex and quadruplex DNA structures have been compared to experimental thermodynamic measurements and by molecular modeling investigation leading to putative binding modes. Taken together these findings contribute to define this compound as potential Multitarget-Directed Ligands interacting simultaneously with different biological targets.

Potent inhibition of Norwalk virus by cyclic sulfamide derivatives

A new class of compounds that exhibit anti-norovirus activity in a cell-based system and embody in their structure a cyclosulfamide scaffold has been identified. The structure of the initial hit (compound 2a, ED50 4 μM, TD50 50 μM) has been prospected by exploiting multiple points of diversity and generating appropriate structure-activity relationships.

BIARYL-SUBSTITUTED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S

Biaryl-substituted tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions media