1326229-56-4

Upstream product

• 1611455-08-3 [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]-4-(tert-butoxycarbonylamino)-2-fluoro-benzoate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 446-31-1 2-fluoro-4-aminobenzoic acid 

Downstream Products

• 1355481-57-0 2'-fluorofolic acid dimethyl ester benzenesulfonate 
• 1355481-59-2 2'-fluoro-N₁₀-formylfolic acid dimethyl ester 
• 1355481-61-6 N₂-(N,N-dimethylaminomethylene)-2'-fluoro-N₁₀-formylfolic acid dimethyl ester 
• 578-12-1 2'-fluorofolic acid 
• 1355481-41-2 di-tert-butyl N-[4-(tert-butoxycarbonylamino)-2-fluorobenzoyl]-L-glutamate 
• 1611455-08-3 [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]-4-(tert-butoxycarbonylamino)-2-fluoro-benzoate 
• 1611455-09-4 [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]-4-amino-2-fluoro-benzoate 

Relevant academic research and scientific papers

PHENYLETHYLPYRIDINE DERIVATIVES AS PDE4-INHIBITORS

The invention relates to novel compounds which are both inhibitors of the phosphodiesterase 4 (PDE4) enzyme and muscarinic M3 receptor antagonists, methods of preparing such compounds, compositions containing them and therapeutic use thereof.

NOVEL COMPOUNDS

Compounds of formula (I) defined herein are both inhibitors of the phosphodiesterase 4 (PDE4) enzyme and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of a disease of the respiratory tract characterized by airway obstruction.

Synthesis of precursors for 18F-labeling of folic acid for PET application

Radiolabeled folate derivatives have the potential to target folate receptor-positive tumor cells for noninvasive diagnosis via positron emission tomography (PET) and single photon emission computed tomography (SPECT). We report the regiospecific synthesis of N2-(N,N-dimethylaminomethylene) -2′-nitrofolic acid di-tert-butyl ester (13) and N2-(N,N- dimethylaminomethylene)-N10-formyl-2′-nitrofolic acid dimethyl ester (25), which are precursors for the radiolabeling of folic acid with the PET isotope 18F. A modular synthetic strategy was applied: Fmoc- and Boc-protected 4-amino-2-nitrobenzoic acid were linked via amide bonds to di-tert-butyl l-glutamate and dimethyl l-glutamate, respectively, to form building blocks 10 and 19. After Fmoc and Boc removal, both compounds were coupled to 6-(bromomethyl)pterin hydrobromide to give crude 2′-nitrofolic acid di-tert-butyl ester and 2′-nitrofolic acid dimethyl ester. After formylation of 2′-nitrofolic acid dimethyl ester at N10 and the introduction of an N,N-dimethylaminomethylene group at N2, precursor 25 was obtained in an overall yield of 3%. The analogous 2′- fluoroderivative 28 was obtained in 7% overall yield from 4-amino-2- fluorobenzoic acid. Precursor 13 was obtained from 2′-nitrofolic acid di-tert-butyl ester in 6% yield after N2-protection. The synthesis of the reference materials 2′-nitro- and 2′-fluorofolic acid was achieved by the reaction of N-(4-amino-2-nitrobenzoyl)- and N-(4-amino-2- fluorobenzoyl)-l-glutamic acid with 6-(bromomethyl)pterin hydrobromide, giving 7% and 14% overall yield, respectively. Georg Thieme Verlag Stuttgart. New York.