Covalent inhibitors of equine encephalitis virus
AssigneeJackson State University
InventorsIfedayo Victor Ogungbe, Huaisheng Zhang
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Abstract
Embodiments and methods for a new class of potent non-peptidic covalent inhibitors of nsP2 cysteine protease that inhibit Venezuelan equine encephalitis virus's (VEEV) replication in neuroblasts are disclosed. More particularly, an acrylate and vinyl sulfone-based chemical series were investigated as promising starting scaffolds against VEEV and as inhibitors of the cysteine protease domain of VEEV's non-structural protein 2 (nsP2). The invention discloses compounds of Formula I and analogues for treatment of VEEV.
Claims18
A composition comprising a compound configured to act as an inhibitor of the cysteine protease domain of Venezuelan equine encephalitis virus (VEEV's) non-structural protein 2 (nsp2), wherein the compound has the Formula (I):
- or a stereoisomer, solvate and/or pharmaceutical acceptable salt thereof;
- wherein
- A is C(O)OR3 or S(O2)R3;
- R3 is (C1-6)alkyl, (C3-7) cycloalkyl, (C3-7)cycloalkyl(C1-5)alkyl, optionally substituted aryl, or optionally substituted (C6-12)aralkyl;
- R1 and R2 are independently selected from H, (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-5)alkyl, optionally substituted aryl, or optionally substituted (C6-12)aralkyl;
- R is a group selected from
- is a single bond or double bond.
A method of treating infectious disease caused by Venezuelan equine encephalitis virus (VEEV) comprising administering a compound to the patient, wherein the compound has the Formula (I):
- or a stereoisomer, solvate and/or pharmaceutical acceptable salt thereof;
- wherein
- A is C(O)OR3 or S(O2)R3;
- R3 is (C1-6)alkyl, (C3-7) cycloalkyl, (C3-7)cycloalkyl(C1-5)alkyl, optionally substituted aryl, or optionally substituted (C6-12)aralkyl;
- R1 and R2 are independently selected from H, (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-5)alkyl, optionally substituted aryl, or optionally substituted (C6-12)aralkyl;
- R is a group selected from
- is a single bond or double bond.
A composition comprising a compound configured to act as an inhibitor of the cysteine protease domain of Venezuelan equine encephalitis virus (VEEV's) non-structural protein 2 (nsp2), wherein the compound has the Formula (III):
- or a stereoisomer, solvate and/or pharmaceutical acceptable salt thereof;
- wherein
- R4 is (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-5)alkyl, optionally substituted aryl, or optionally substituted (C6-12)aralkyl;
- R5 and R6 are independently selected from H, (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-5)alkyl, optionally substituted aryl, or optionally substituted (C6-12)aralkyl;
- R7 is a group selected from
A method of treating infection by Venezuelan equine encephalitis virus (VEEV) comprising administering a compound to the patient, wherein the compound has the Formula (III):
- or a stereoisomer, solvate and/or pharmaceutical acceptable salt thereof;
- wherein
- R4 is (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-5)alkyl, optionally substituted aryl, or optionally substituted (C6-12)aralkyl;
- R5 and R6 are independently selected from H, (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C1-5)alkyl, optionally substituted aryl, or optionally substituted (C6-12)aralkyl;
- R7 is a group selected from
Dependencies are inferred from the claim text.