173604-87-0Relevant articles and documents
PRODRUGS OF THE TYROSINE KINASE INHIBITOR FOR TREATING CANCER
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Paragraph 00189-00190, (2021/03/05)
There are provided compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, useful for inhibition or modulation of the activity of tyrosine kinases and treatment of disease states or conditions mediated by tyrosine kinases, including cancers. (I)
DERIVATIVES OF RELEBACTAM AND USES THEREOF
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Paragraph 1364-1366; 1766-1767, (2020/04/24)
Derivatives of relebactam, therapeutic methods of using the derivatives of relebactam, particularly in combination with β-lactam antibiotics and pharmaceutical compositions thereof are disclosed. The derivatives of relebactam are suitable for oral administration.
Coupling of an Acyl Migration Prodrug Strategy with Bio-activation to Improve Oral Delivery of the HIV-1 Protease Inhibitor Atazanavir
Subbaiah, Murugaiah A. M.,Meanwell, Nicholas A.,Kadow, John F.,Subramani, Lakshumanan,Annadurai, Mathiazhagan,Ramar, Thangeswaran,Desai, Salil D.,Sinha, Sarmistha,Subramanian, Murali,Mandlekar, Sandhya,Sridhar, Srikanth,Padmanabhan, Shweta,Bhutani, Priyadeep,Arla, Rambabu,Jenkins, Susan M.,Krystal, Mark R.,Wang, Chunfu,Sarabu, Ramakanth
, p. 4176 - 4188 (2018/05/23)
HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat HIV-1 infection. However, they are characterized by poor oral bioavailability and a need for boosting with a pharmacokinetic enhancer, which results in additional drug-drug interactions that are sometimes difficult to manage. We investigated a chemo-activated, acyl migration-based prodrug design approach to improve the pharmacokinetic profile of 1 but failed to obtain improved oral bioavailability over dosing the parent drug in rats. This strategy was refined by conjugating the amine with a promoiety designed to undergo bio-activation, as a means of modulating the subsequent chemo-activation. This culminated in a lead prodrug that (1) yielded substantially better oral drug delivery of 1 when compared to the parent itself, the simple acyl migration-based prodrug, and the corresponding simple l-Val prodrug, (2) acted as a depot which resulted in a sustained release of the parent drug in vivo, and (3) offered the benefit of mitigating the pH-dependent absorption associated with 1, thereby potentially reducing the risk of decreased bioavailability with concurrent use of stomach-acid-reducing drugs.