Structural Examination of 6-Methylsulphonylphenanthro- [9,10-C]-furan-1(3H)-one—A Rofecoxib Degradation Product 英文参考文献.docVIP

Pharmaceuticals 2010, 3, 369-378; doi:10.3390/ph3020369 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Article Structural Examination of 6-Methylsulphonylphenanthro- [9,10-C]-furan-1(3H)-one—A Rofecoxib Degradation Product Pamela M. Dean Department of Chemistry, Monash University, Wellington Road, Clayton, Victoria, 3800, Australia; E-Mail: pamela.dean@.au; Tel.: +61-3-990-54599; Fax: +61-3-990-54597 Received: 14 December 2009; in revised form: 12 January 2010 / Accepted: 21 January 2010 / Published: 1 February 2010 Abstract: In the attempt to discover a new polymorph of rofecoxib (Vioxx?), an unexpected product resulted. The product was characterised by chemical composition, thermal behaviour and structure and found to be 6-methylsulphonylphenanthro-[9,10-C] furan-1(3H)-one, a photo-cyclization degradation product of rofecoxib. This is a significant finding because it indicates that without appropriate control of the recrystallisation procedures, the structural integrity of rofecoxib may be seriously compromised. Keywords: rofecoxib; structural characterisation; NSAID; crystallography 1. Introduction The therapeutic properties of willow bark were known since antiquity, with the Egyptians and Assyrians using a decoction of myrtle and willow leaves to produce analgesia. Even Hippocrates, regarded as the father of medicine, recommended the chewing of willow leaves for this purpose. The active compound within willow bark was subsequently characterised and synthetically modified in 1875 by Felix Hoffman from the Bayer Company to form acetylsalicylic acid, commonly known as aspirin, (Figure 1) [1]. Subsequently in the 20th century aspirin was discovered to exert in addition antipyretic and anti-inflammatory effects, thereby becoming the first known anti-inflammatory. Thereafter a plethora of anti-inflammatory drugs were synthesized, notably