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Upstream product

• 504-24-5 4-aminopyridine 
• 1170233-95-0 C₂₁H₂₄N₂O₅S 
• 629-03-8 1 ,6-dibromohexane 
• 24566-79-8 2-(6-bromohexyl)isoindole-1,3-dione 
• 1170233-97-2 6-amino-N-(benzyloxy)-N-(2-morpholinoethyl)hexane-1-sulfonamide 
• 6633-95-0 6-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)hexanesulfonyl chloride 

Relevant academic research and scientific papers

Nicotinamide phosphoribosyltransferase inhibitors, design, preparation, and structure-activity relationship

Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. By using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described, and the compounds are optimized. Compounds are designed inspired by the NAMPT inhibitor APO866 and cyanoguanidine inhibitor scaffolds. In comparison with recently published derivatives, the new analogues exhibit an equally potent antiproliferative activity in vitro and comparable activity in vivo. The best performing compounds from these series showed subnanomolar antiproliferative activity toward a series of cancer cell lines (compound 15: IC50 0.025 and 0.33 nM, in A2780 (ovarian carcinoma) and MCF-7 (breast), respectively) and potent antitumor in vivo activity in well-tolerated doses in a xenograft model. In an A2780 xenograft mouse model with large tumors (500 mm3), compound 15 reduced the tumor volume to one-fifth of the starting volume at a dose of 3 mg/kg administered ip, bid, days 1-9. Thus, compounds found in this study compared favorably with compounds already in the clinic and warrant further investigation as promising lead molecules for the inhibition of NAMPT.

NOVEL CYANOGUANIDINES

This application discloses novel cyanoguanidines of the formula (I) wherein A is selected from -C(=O)-, -S(=O)2-, -C(=S)-, and -P(=O)(R5)-, wherein R5 is selected from C1-6-alkyl, C1-6-alkoxy, and hydroxy; B is selected from a single bond, -O-, -NR6- and -C(=O)-NR6-, wherein R6 is selected from hydrogen, optionally substituted C1-12-alkyl, optionally substituted C1-12-alkenyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl; and m is an integer of 0-12 and n is an integer of 0-12, wherein the sum m+n is 1-20; and R1 is selected from optionally substituted heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The compounds are usefuld for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT).