| Structural highlights
Publication Abstract from PubMed
A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.
Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group.,Bungard CJ, Williams PD, Ballard JE, Bennett DJ, Beaulieu C, Bahnck-Teets C, Carroll SS, Chang RK, Dubost DC, Fay JF, Diamond TL, Greshock TJ, Hao L, Holloway MK, Felock PJ, Gesell JJ, Su HP, Manikowski JJ, McKay DJ, Miller M, Min X, Molinaro C, Moradei OM, Nantermet PG, Nadeau C, Sanchez RI, Satyanarayana T, Shipe WD, Singh SK, Truong VL, Vijayasaradhi S, Wiscount CM, Vacca JP, Crane SN, McCauley JA ACS Med Chem Lett. 2016 May 9;7(7):702-7. doi: 10.1021/acsmedchemlett.6b00135., eCollection 2016 Jul 14. PMID:27437081[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bungard CJ, Williams PD, Ballard JE, Bennett DJ, Beaulieu C, Bahnck-Teets C, Carroll SS, Chang RK, Dubost DC, Fay JF, Diamond TL, Greshock TJ, Hao L, Holloway MK, Felock PJ, Gesell JJ, Su HP, Manikowski JJ, McKay DJ, Miller M, Min X, Molinaro C, Moradei OM, Nantermet PG, Nadeau C, Sanchez RI, Satyanarayana T, Shipe WD, Singh SK, Truong VL, Vijayasaradhi S, Wiscount CM, Vacca JP, Crane SN, McCauley JA. Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group. ACS Med Chem Lett. 2016 May 9;7(7):702-7. doi: 10.1021/acsmedchemlett.6b00135., eCollection 2016 Jul 14. PMID:27437081 doi:http://dx.doi.org/10.1021/acsmedchemlett.6b00135
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