Pyrrolidine-Containing Bisphosphonates as Potential Anti-Resorption Bone Drugs.
Bisphosphonates, particularly those with N-substituted groups, are currently the most popular drugs for the treatment of osteoporosis. However, their chemical structures are still rather simple and new synthetic methods are needed to expand their molecular complexity and also improve their specificity of action towards other targets as anticancer, antibacterial, and antimalarial drugs. Herein, we report a new class of potential antiresorption bisphosphonate drugs that have a pyrrolidine unit with different substituents, obtained through a simple dipolar cycloaddition reaction between azomethine ylides and vinylidenebisphosphonate derivatives as precursors. The methodology led to the efficient preparation of a wide range of (1-methylpyrrolidine-3,3-diyl)bis(phosphonic esters) derivatives with different substituents in position 4.
Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari Venezia, via Torino 155, 30170, Venezia Mestre, Italy.
Lorena
L
De Luca
Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari Venezia, via Torino 155, 30170, Venezia Mestre, Italy.
Andrea
A
Chiminazzo
Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari Venezia, via Torino 155, 30170, Venezia Mestre, Italy.
Laura
L
Sperni
Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari Venezia, via Torino 155, 30170, Venezia Mestre, Italy.
Giorgio
http://orcid.org/0000-0001-8942-8254
G
Strukul
Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari Venezia, via Torino 155, 30170, Venezia Mestre, Italy.
Alessandro
http://orcid.org/0000-0001-6114-9181
A
Scarso
D050071:Bone Density Conservation Agents / Q000138:chemical synthesis*; D061565:Cycloaddition Reaction; D004164:Diphosphonates / Q000138:chemical synthesis*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis*
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D011759:Pyrrolidines
cycloaddition; phosphorous; pyrrolidine; ylides