286844-91-5Relevant articles and documents
The development of a large-scale synthesis of matrix metalloproteinase inhibitor, ABT-518
Chang, Sou-Jen,Fernando, Dilinie,Fickes, Michael,Gupta, Ashok K.,Hill, David R.,McDermott, Todd,Parekh, Shyamal,Tian, Zhenping,Wittenberger, Steven J.
, p. 329 - 335 (2002)
A process for the preparation of matrix metalloproteinase inhibitor ABT-518 has been developed. Significant improvements have been made to the first generation synthesis and are described here. The new process is very robust and efficient; multikilogram quantities of the title compound have been synthesized for clinical trials. ABT-518 was prepared by this six-step synthetic sequence in 51% overall yield with >99% ee.
Phenoxyphenyl sulfone N-formylhydroxylamines (Retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors
Wada,Holms,Curtin,Dai,Florjancic,Garland,Guo,Heyman,Stacey,Steinman,Albert,Bouska,Elmore,Goodfellow,Marcotte,Tapang,Morgan,Michaelides,Davidsen
, p. 219 - 232 (2007/10/03)
A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and -9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1′ substituent with a phenoxyphenyl group provided compounds that are highly selective for inhibition of MMP-2 and -9 over MMP-1. Optimization of the substituent adjacent to the retrohydroxamate center in this series led to the clinical candidate ABT-518 (6), a.highly potent, selective, orally bioavailable MMP inhibitor that has been shown to significantly inhibit tumor growth in animal cancer models.
Process for the selective N-formylation of N-hydroxylamines
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, (2008/06/13)
The instant invention provides a process for the selective N-formylation of N-hydroxylamines.