- FLUOROALKYL-OXADIAZOLES AND USES THEREOF
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Provided herein are compounds identified as inhibitors of HDAC6 activity that can be used to treat various diseases and disorders.
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- Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion
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RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC50 of 1.2 nM against a panel of RSV A and B laboratory strains and clinical isolates with antiviral efficacy in the Balb/C mouse model of RSV infection. Oral bioavailability in preclinical species ranged from 42 to >100% with evidence of highly efficient penetration into lung tissue. In healthy adult human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a significant reduction in viral load and symptoms compared to placebo.
- Cockerill, G. Stuart,Angell, Richard M.,Bedernjak, Alexandre,Chuckowree, Irina,Fraser, Ian,Gascon-Simorte, Jose,Gilman, Morgan S. A.,Good, James A. D.,Harland, Rachel,Johnson, Sara M.,Ludes-Meyers, John H,Littler, Edward,Lumley, James,Lunn, Graham,Mathews, Neil,McLellan, Jason S.,Paradowski, Michael,Peeples, Mark E.,Scott, Claire,Tait, Dereck,Taylor, Geraldine,Thom, Michelle,Thomas, Elaine,Villalonga Barber, Carol,Ward, Simon E.,Watterson, Daniel,Williams, Gareth,Young, Paul,Powell, Kenneth
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supporting information
p. 3658 - 3676
(2021/04/12)
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- SPIRO-INDOLINES FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS INFECTION (RSV)
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Benzimidazoles of formula (I): wherein: one of X and Y is an N atom or a substituted C atom, and the other is CH; L is a single bond, C1-3 alkylene, C2-3 alkenylene or C2-3 alkynylene; R1 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 3- to 10-membered cycloalkyl, 5- to 10-membered heterocyclyl or 5- to 12- membered heteroaryl, each of which is unsubstituted or substituted; Z is halo, C1-6 haloalkyl, nitro, -CN, -N(R2)2, -OR2, -SR2, -S(=0)R2, or -S(=0)2R2; each R2 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein said alkyl, alkenyl and alkynyl groups are unsubstituted or substituted; and m is 0 or 1; and the pharmaceutically acceptable salt thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection.
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Page/Page column 38; 39
(2016/05/02)
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- NOVEL AZA-OXO-INDOLES FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS INFECTION
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The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5, W and X are as described herein, compositions including the compounds and methods of using the compounds.
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- NOVEL AZA-OXO-INDOLES FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS INFECTION
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The invention provides novel compounds having the general formula:(I) wherein R1, R2, R3, R4, W and X are as described herein, compositions including the compounds and methods of using the compounds.
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