206879-94-9

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 294210-79-0 1-(3-nitro-phenyl)-piperazine hydrochloride 
• 585-79-5 m-nitrobromobenzene 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 294210-79-0 1-(3-nitrophenyl)piperazine monohydrochloride 
• 402-67-5 3-fluoro-1-nitrobenzene 
• 34619-03-9 tert-butyldicarbonate 
• 54054-85-2 1-(3-nitrophenyl)piperazine 

Downstream Products

• 54054-85-2 1-(3-nitrophenyl)piperazine 
• 1374215-26-5 C₃₀H₃₆N₆O₃ 
• 1374213-83-8 6-(3-(4-acetylpiperazin-1-yl)phenylamino)-4-(1-phenylcyclopropylamino)nicotinamide 
• 1374213-82-7 4-(1-phenylcyclopropylamino)-6-(3-(piperazin-1-yl)phenylamino)nicotinamide 
• 206879-72-3 4-(3-amino-phenyl)-piperazine-1-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

NOTCH INHIBITORS AND USES THEREOF

Disclosed herein, inter alia, are compounds for inhibiting Notch and uses thereof.

Synthesis and structure-activity relationships of new 2-phenoxybenzamides with antiplasmodial activity

The 2-phenoxybenzamide 1 from the Medicines for Malaria Venture Malaria Box Project has shown promising multi-stage activity against different strains of P. falciparum. It was successfully synthesized via a retrosynthetic approach. Subsequently, twenty-one new derivatives were prepared and tested for their in vitro activity against blood stages of the NF54 strain of P. falciparum. Several insights into structure-activity relationships were revealed. The antiplasmodial activity and cytotoxicity of compounds strongly depended on the substitution pattern of the anilino partial structure as well as on the size of substituents. The diaryl ether partial structure had further impacts on the activity. Additionally, several physicochemical and pharmacokinetic parameters were calculated (log P, log D7.4 and ligand efficiency) or determined experimentally (passive permeability and CYP3A4 inhibition). The tert-butyl-4-{4-[2-(4-fluorophenoxy)-3-(trifluoromethyl)benzamido]phenyl}piperazine-1-carboxylate possesses high antiplasmodial activity against P. falciparum NF54 (PfNF54 IC50 = 0.2690 μM) and very low cytotoxicity (L-6 cells IC50 = 124.0 μM) resulting in an excellent selectivity index of 460. Compared to the lead structure 1 the antiplasmodial activity was improved as well as the physicochemical and some pharmacokinetic parameters.

MONOACYLGLYCEROL LIPASE INHIBITORS

Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).

PROTEIN KINASE INHIBITORS AND USES THEREOF FOR THE TREATMENT OF DISEASES AND CONDITIONS

Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2) and/or receptor interacting kinase 3 (RIPK3). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 or RIPK3 could provide therapeutic benefit. Compounds that function as RIPK3 inhibitors provide therapeutic benefit in the treatment of inflammatory and degenerative conditions.

Covalent inhibition of the histamine H3 receptor

Covalent binding of G protein-coupled receptors by small molecules is a useful approach for better understanding of the structure and function of these proteins. We designed, synthesized and characterized a series of 6 potential covalent ligands for the histamine H3 receptor (H3R). Starting from a 2-amino-pyrimidine scaffold, optimization of anchor moiety and warhead followed by fine-tuning of the required reactivity via scaffold hopping resulted in the isothiocyanate H3R ligand 44. It shows high reactivity toward glutathione combined with appropriate stability in water and reacts selectively with the cysteine sidechain in a model nonapeptide equipped with nucleophilic residues. The covalent interaction of 44 with H3R was validated with washout experiments and leads to inverse agonism on H3R. Irreversible binder 44 (VUF15662) may serve as a useful tool compound to stabilize the inactive H3R conformation and to study the consequences of prolonged inhibition of the H3R.

PYRIDO[2,3-D]PYRIMIDIN-7ONES AND RELATED COMPOUNDS AS INHIBITORS OF PROTEIN KINASES

Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds having the structures below (I) are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit.

MACROCYLIC PYRIMIDINE DERIVATIVES

The present invention relates to substituted macrocylic pyrimidine derivatives of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention have EF2K inhibitory activity and optionally also Vps34 inhibitory activity. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

NICOTINAMIDES AS JAK KINASE MODULATORS

The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of JAK kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition JAK kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by JAK kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

PREPARATION AND USES OF 1,2,4-TRIAZOLO [1,5a] PYRIDINE DERIVATIVES

This application relates to compounds of the general Formula I and salts thereof, wherein X, R1A, R1B, R2, R3, R4, and R5 are as defined herein. The application also relates to compositions and methods of treatment of hyperproliferative diseases or disorders.

5-OXO-5,8-DIHYDRO-PYRIDO-PYRIMIDINES AS INHIBITORS OF C-FMS KINASE

The invention addresses the current need for selective and potent protein tyrosine kinase inhibitors by providing potent inhibitors of c-fms kinase. The invention is directed to the novel compounds of Formula I: or a salt, stereoisomer, tautomer, crystalline, polymorph, amorphous, solvate, hydrate, ester, prodrug or metabolite form thereof, wherein A, Y, Z, R101 and R200 are described in the specification.