2037-99-2Relevant articles and documents
Design and synthesis of novel bone-targeting dual-action pro-drugs for the treatment and reversal of osteoporosis
Arns, Steve,Gibe, Romelo,Moreau, Anne,Monzur Morshed,Young, Robert N.
, p. 2131 - 2140 (2012/05/05)
There is an important medical need for effective therapies to redress the general bone loss associated with advanced osteoporosis. Prostaglandin E 2 and related EP4 receptor agonists have been shown to stimulate bone regrowth but their use has been limited by systemic side effects. Herein is described the design and synthesis of novel dual-action bone-targeting conjugate pro-drugs where two classes of active agents, a bone growth stimulating prostaglandin E2 EP4 receptor subtype agonist (5 or 6) and a bone resorption inhibitor bisphosphonate, alendronic acid (1), are coupled using metabolically labile carbamate or 4-hydroxyphenylacetic acid based linkers. Radiolabelled conjugates 9, 11a/b and 25 were synthesized and evaluated in vivo in rats for uptake of the conjugate into bone and subsequent release of the EP4 agonists over time. While conjugate 11a/b was taken up (9.0% of initial dose) but not released over two weeks, conjugates 9 and 25 were absorbed at 9.4% and 5.9% uptake of the initial dose and slowly released with half-lives of approximately 2 weeks and 5 days respectively. These conjugates were well tolerated and offer potential for sustained release and dual synergistic activity through their selective bone targeting and local release of the complimentary active components.
N-alkylation of imides using phase transfer catalysts under solvent-free conditions
Jaskowska, Jolanta,Kowalski, Piotr
scheme or table, p. 1371 - 1375 (2009/04/07)
(Chemical Equation Presented) N-Alkylation of imides in the reaction of imides and alkylhalides, catalyzed by PT catalysts under solvent-free conditions, has been developed. The reaction occurs in the presence of K 2CO3, and in many cases it takes place spontaneously. In the N-benzylation reaction, it has been recognized that TBAB (tetrabutylammonium bromide) and TBATFB (tetrabutylammonium tetrafluoroborate) show highest catalytic effect. Versatility and synthetic capacity of the solvent-free alkylation has been confirmed by N-benzylation and N-ethylation of various imides. The developed procedure gives easy access to N-(ω-bromoalkyl) imides.
3-Benzyl-2H-1,3-benzoxazine-2,4(3H)-diones, a new group of antimycobacterial compounds against potentially pathogenic strains
Waisser, Karel,Perina, Milan,Kunes, Jiri,Klimesova, Vera,Kaustova, Jarmila
, p. 1137 - 1149 (2007/10/03)
A series of derivatives of 3-benzyl-2H-benzoxazine-2,4(3H)-dione substituted in positions 6, 7 or 8 on the benzoxazine, and in positions 3 or 4 on the benzyl moiety was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of Mycobacterium kansasii. The disadvantage of the compounds is in their low solubility in water. The antimycobacterial activity of N-benzylsalicylamides correlates with that of 3-benzyl-2H-1,3-benzoxazin-2,4(3H)-diones and depends on the partition coefficients and electronic indexes.