Spiropyrrolidine derived antiviral agents
Inventors
Cao, Hui • Zhang, Jiajun • Xing, Xuechao • Rhodes, Matthew C. • Gao, Xuri • Li, Wei • Or, Yat Sun
Assignees
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Publication Number
US-12145942-B2
Publication Date
2024-11-19
Expiration Date
Abstract
The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof: which inhibit picornavirus, norovirus or coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a virus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.
Core Innovation
The invention relates to a compound represented by Formula (I), or a pharmaceutically acceptable salt thereof. The compounds are defined by selecting substituents and structural components from enumerated classes, including optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups. Several substituent pairs are taken together to form optionally substituted carbocyclic or heterocyclic rings, including partially unsaturated ring variants.
The structural scope further specifies the selection of R4 as hydrogen, optionally substituted alkyl, alkenyl, cycloalkyl, or particular functional and prodrug moiety options, and defines B as an optionally substituted aryl or optionally substituted heteroaryl. X is selected from a set of moieties that include cyano, carbonyl-containing groups, sulfonyl-containing substituent forms, and various unsaturated linkage patterns, with w selected from 1, 2, 3, 4, or 5. R13 and R14 are independently selected from the enumerated substituent classes, with an alternative where they are taken together with a nitrogen atom to form an optionally substituted heterocyclic ring.
Preferred compound embodiments are represented by multiple enumerated structural variants, including Formulae (IV-1A) to (IV-5A), Formulae (V-1) to (V-5), Formulae (V-1A) to (V-5A), and further structural classes including VI, VI′, VI″, VI‴, VII, VIII, VIII′, VIII-A, VIII-B, IX-1 to IX-5 and IX-1A to IX-5A, X-1 to X-5 and X-1A to X-5A, XI-1 to XI-3, XII-1 to XII-3, XIII-1 to XIII-3, and XIV-1 to XIV-3. The excerpt also notes applicability to pharmaceutically acceptable salts, esters, and prodrugs.
Claims Coverage
The provided claims center on one independent compound claim and one independent method claim. In total, 2 inventive features are identified across the independent claims.
Formula (I) compound or pharmaceutically acceptable salt
A compound represented by Formula (I), or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, R21, R22, and R23 are each independently selected from hydrogen; optionally substituted C1–C8 alkyl, C2–C8 alkenyl, or C2–C8 alkynyl; optionally substituted C3–C8 cycloalkyl; optionally substituted 3- to 8-membered heterocycloalkyl; optionally substituted aryl, arylalkyl, heteroaryl, and heteroarylalkyl; and further ring-forming alternatives where selected substituents are taken together to form optionally substituted carbocyclic or heterocyclic rings or optionally substituted partially unsaturated rings. The claim further defines R24, R25, R4, B, X, R13, R14, R15, and R16 through enumerated selections and ring-forming alternatives, including options where R13 and R14 form an optionally substituted heterocyclic ring, and where R23 and R24 are taken together with the nitrogen atom to form an optionally substituted heterocyclic ring.
Virus 3C protease or 3CL protease inhibition in a mammal
A method for inhibiting viral 3C protease or viral 3CL protease in a mammal by administering a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.
The claims cover a Formula (I) compound with broadly enumerated substituent classes and ring-forming combinations, together with a method centered on inhibiting viral 3C protease or viral 3CL protease in a mammal using a therapeutically effective amount of the claim 1 compound.
Stated Advantages
Provides antiviral agents that inhibit viral 3C/3CL-like proteases.
Useful for treating or preventing virus infection by administering a therapeutically effective amount in a mammal.
Enables treatment of respiratory disorder by administering a therapeutically effective amount of the defined compound.
Antiviral activity for treating and preventing viral infections including picornavirus, norovirus, and coronavirus.
Documented Applications
Inhibiting viral 3C protease or viral 3CL protease in a mammal by administering a therapeutically effective amount of a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof.
Treating a respiratory disorder by administering a therapeutically effective amount of a compound represented by Formula (I) or a pharmaceutically acceptable salt to a subject in need thereof.
Performing the method using a coronavirus selected from 229E, NL63, OC43, HKU1, SARS-COV, or MERS coronavirus.
Treating or preventing virus infection by administering a therapeutically effective amount of the defined compound in a mammal.
Treating and preventing viral infections (picornavirus, norovirus, coronavirus) using Formula (I) compounds.
Inhibiting viral 3C protease or viral 3CL protease in a mammal by administering a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof.
Treating a respiratory disorder by administering a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt, to a subject in need thereof.
Performing the method of claim 8 using a coronavirus selected from 229E, NL63, OC43, HKU1, SARS-COV, or MERS coronavirus.
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