Structure-activity relationships of proline modifications around the tetracyclic-indole class of NS5A inhibitors.
We describe the impact of proline modifications, in our tetracyclic-indole based series of nonstructural protein 5A (NS5A) inhibitors, to their replicon profiles. This work identified NS5A inhibitors with an improved and flattened resistance profiles.
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA. Electronic address: ling.tong@merck.com.
Ling
L
Tong
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Wensheng
W
Yu
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Craig A
CA
Coburn
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Lei
L
Chen
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Oleg
O
Selyutin
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Qingbei
Q
Zeng
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Michael P
MP
Dwyer
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Anilkumar G
AG
Nair
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Bandarpalle B
BB
Shankar
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Seong Heon
SH
Kim
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
De-Yi
DY
Yang
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Stuart B
SB
Rosenblum
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Rebecca T
RT
Ruck
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Ian W
IW
Davies
Department of Medicinal Chemistry, WuXi AppTec, Shanghai 200131, China.
Bin
B
Hu
Department of Medicinal Chemistry, WuXi AppTec, Shanghai 200131, China.
Bin
B
Zhong
Department of Medicinal Chemistry, WuXi AppTec, Shanghai 200131, China.
Jinglai
J
Hao
Department of Medicinal Chemistry, WuXi AppTec, Shanghai 200131, China.
Tao
T
Ji
Department of Medicinal Chemistry, WuXi AppTec, Shanghai 200131, China.
Shuai
S
Zan
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Rong
R
Liu
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Sony
S
Agrawal
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Donna
D
Carr
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Stephanie
S
Curry
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Patricia
P
McMonagle
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Karin
K
Bystol
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Frederick
F
Lahser
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Paul
P
Ingravallo
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Shiying
S
Chen
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Ernest
E
Asante-Appiah
Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Joseph A
JA
Kozlowski
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D001572:Benzofurans; D007093:Imidazoles; D007211:Indoles; D011392:Proline; D017361:Viral Nonstructural Proteins; C000589335:elbasvir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
Direct-acting antiviral agents; Elbasvir; HCV NS5A inhibitor; HCV infection treatment; Indole based tetracyclic core; MK-8742