263552-95-0Relevant academic research and scientific papers
Method of treating bone loss by stimulation of calcitonin
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, (2008/06/13)
Compounds of the formula R1and R2are independently alkyl of 1 to 6 carbon atoms, allyl, or substituted allyl of 3 to 6 carbon atoms; R3is hydrogen, alkyl of 1 to 6 carbon atoms, or cycloalkyl of 3 to 10 carbon atoms; and R4is phenyl or naphthyl substituted with alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms or NR5R6; substituted or unsubstituted phenylalkyl wherein the alkyl group contains 1 to 6 carbon atoms; substituted or unsubstituted 5 to 10 membered heteroaryl having 1 to 3 heteroatoms selected from N, S and O; substituted or unsubstituted cycloalkyl of 3 to 10 carbon atoms; or substituted or unsubstituted cycloalkylalkyl of 4 to 10 carbon atoms; provided that phenyl or naphthyl is substituted with NR5R6when R1and R2 is alkyl, are useful in the treatment of various disorders associated bone loss by increased transcription and elevation of plasma calcitonin levels. Such disorders include, but are not limited to: Paget's Disease, post menopausal osteoporosis, senile osteoporosis, and glucocorticoid-induced osteoporosis.
Novel and selective calcitonin-inducing agents
Gilbert, Adam M.,Caltabiano, Stephen,Roberts, Denise,Sum, Sam F. W.,Francisco, Gerardo D.,Lim, Kitae,Asselin, Magda,Ellingboe, John W.,Kharode, Yogendra,Cannistraci, Anna,Francis, Rita,TrailSmith, Mark,Gralnick, David
, p. 1223 - 1233 (2007/10/03)
A series of xanthine sulfonamides is presented as a class of calcitonin (CT) inducers - a potentially new method for treating diseases associated with postmenopausal bone loss such as osteoporosis. We have found that certain di-n-butylxanthine sulfonamides 4 upregulate CT transcription in a CT-luciferase reporter gene assay (CT-luci) and increase the production and release of CT in a CT secretion/RIA assay (CTS). In addition, these compounds do not have potent PDE4 inhibitory activity as do the related xanthine methylene ketones such as denbufyllene (2). One compound in particular (9) shows a transcription activation ratio (TAR) of 2.1 in CT-luci, a CTS increase of 3.6-fold, and a PDE4 (phosphodiesterase type IV) IC50 = 4.1 μM. In addition, this compound showed a statistically significant 47% trabecular bone protection in ovariectomized-induced osteopenia (OVX) rats as determined by assay when administered for 4 weeks at 30 mg/kg/day, i.p. by quantitative computed tomography (QCT). When administered p.o., compound 9 shows 50% trabecular bone protection when administered for 3 weeks at 50 mg/kg/day, i.p. This compared with salmon CT which shows 62% trabecular bone protection when administered at 50 IU/kg/day for 4 weeks.
