Triptolide derivatives and their uses

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C549S218000

Reexamination Certificate

active

07626044

ABSTRACT:
Triptolide derivatives of Formula (I), their pharmaceutically acceptable salts and optical isomers, Formula (I):wherein, C5 and C6 are connect with each other by a C-C single bond or double bond; when C5 and C6 are connected with C-C single bond, X and Y represent independently hydrogen, oxygen, hydroxyl, halogen, lower alkyl-oxy, lower alkyl-amino, mercapto, lower alkyl-thio, the group of formula —OCOR, —OSO2OR or —OPO(OH)2, each of which is attached to C5 and C6, R represents —(CH2)nCO2Na, —(CO2)nCO2K, or —(CH2)nCH3, wherein n=1-6; Z represents hydrogen, oxygen, hydroxyl, halogen, lower alkyl-oxy, lower alkyl-amino, mercapto, lower alkyl-thio, the group of formula -OCOR, -OSO2OR or —OPO(OH)2, each of which is linked at C14-position, R represents —(CH2)nCO2Na, —(CO2)nCO2K, or —(CH2)nCH2, wherein n=1-6; wherein, the“______” linked with X, Y, and Z represents the stereochemistry orientations “” or “” , but X and Y cannot both be hydrogen atom at the same time, methods for preparing the triptolides and their use as antiphiogistic agent, immunosuppressive agent or therapeutic agent for other related diseases.

REFERENCES:
patent: 1257507 (2000-06-01), None
patent: 1095844 (2002-12-01), None
patent: 1133637 (2004-01-01), None
Progress in research on triptolide (in Chinese), China Journal of Chinese Materia Medica, vol. 30, Issue 3, 170-174, Feb. 2005.
Progress in structure modification of triptolide (in Chinese), Acta Pharmaeutica Sinica 2004, 39(10), 857-864.
Advances in pharmacological research ofTripterygium WilfordiiHook . f. on immune system and inflammatory reaction (in Chinese), Chinese Journal of New Drugs 2004, vol. 13 No. 9, 780-784.
Enantioselective Total Synthesis of (−)-Triptolide, (−)-Triptonide, (+)-Triptophenolide, and (+)-Triptoquinonide, J. Org. Chem., vol. 65, No. 7. 2000, 2208-2217.
Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes, A. Liacini et l Biochamical and Biophysical Research Communications 327 (2005) 320-327.
Triptolide inhibits transcription factor NF-kappaB and induces apoptosis of multiple myeloma cells, Leukemia Research 29 (2005) 99-105.
Triptolide, an Active Component of the Chinese Herbal RemeedyTripterygium wilfordiiHook F, Inhibits Production of Nitric Oxide by Decreasing Inducible Intric Oxide Synthase Gene Transcript, Arthritis & Rheumatism, vol. 50, No. 9, 2004, 2995-3003.

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