IP Library › Granted Patent US 12,590,123
Granted Patent B2
US 12,590,123 · App. 17/620,169 · Granted Mar 31, 2026

Compounds and methods for treating cancer, viral infections, and allergic conditions

Inventors: James W. Janetka (St. Louis, MO); Vishnu Damalanka (St. Louis, MO)
Assignee: Washington University
C07K5/126A61K45/06A61K47/545A61P31/14C07K5/1024
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Quick Facts
Patent No.
US 12,590,123
App. No.
17/620,169
Granted
Mar 31, 2026
Kind
B2
Abstract

The present invention generally relates to compounds that are useful for inhibiting one or more trypsin-like S1 serine proteases, HGFA, matriptase, hepsin, KLK5 and/or TMPRSS2 as well as cysteine proteases including trypsin-like cysteine proteases (e.g. Cathepsin B). The present invention also relates to various methods of using the inhibitor compounds to treat or prevent viral infections, including those caused by coronaviruses and influenza, conditions associated with KLK5, various malignancies, pre-malignant conditions, and cancer.

Claims (26)

1 . A compound of Formula (IIA), (IIB), (IIC), (IID), (IIE), (IIF), (IIG), or (IIH) a salt thereof, or a stereoisomer thereof:

wherein:

each n is independently 1 or 2;

each P 3 is independently hydrogen or a side chain of a natural or unnatural amino acid;

each X is independently hydrogen or methyl;

each Y is independently hydrogen, acetyl, tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethyloxycarbonyl (Fmoc), benzyl, —C(O)R, —SOOR, —COOR, —C(O)NHR, substituted or unsubstituted —(CH 2 ) x aryl, substituted or unsubstituted —(CH 2 ) x heteroaryl, substituted or unsubstituted —(CH 2 ) x cycloalkyl, or substituted or unsubstituted —(CH 2 ) x heterocycle;

each x is independently 0, 1, or 2;

each R is independently C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted alkylheterocycle, aralkyl, or aryl; and

each Z is independently

R 1 is hydrogen,

R 2 and R 3 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroarylalkyl;

R 4 is hydrogen, substituted or unsubstituted alkyl, or a residue of an amino acid, or R 3 and R 4 can form a ring;

each R 5 is independently hydrogen, substituted or unsubstituted alkyl, or R 5 moieties can form a ring; and

each R 6 is substituted or unsubstituted aryl.

2 . The compound of claim 1 wherein the compound of Formula (IIA)-(IIH) includes one or more of the following:

each Y is independently hydrogen, acetyl, tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), or fluorenylmethyloxycarbonyl (Fmoc);

each P 3 is independently a side chain of Ala, Gly, Val, Leu, Lys, Arg, Asn, Phe, Gln, Thr, D-Trp, Tyr, Met, Agp, hCha, hTyr, hPhe, Orn, DAB, DAB(Z), Nle(O-Bzl), Arg(NO 2 ), Arg(Z) 2 , Lys(2-ClZ), hLeu, Dht, Idc, IgI, Chg, hAbu, Hyp, Glu(Bz), Met(O), Dap, Phe(F5), Glu(Me), hArg; or a combination thereof.

3 . The compound of claim 1 wherein R 2 and R 3 are each independently hydrogen, alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroarylalkyl.

4 . The compound of claim 1 wherein R 4 is hydrogen, alkyl, or a residue of an amino acid, or R 3 and R 4 can form a piperazine or piperidine ring.

5 . The compound of claim 1 wherein each R 5 is independently hydrogen, alkyl, or the R 5 moieties can form a ring.

6 . The compound of claim 1 wherein each R 6 is aryl.

7 . The compound of claim 1 wherein each Z is independently:

wherein A is —O— or NH and R 11 is H, methyl, benzyl, optionally substituted alkyl, optionally substituted aryl, heterocycle, or a residue of an α-amino acid.

8 . The compound of claim 7 wherein A is NH and A and R 11 form a residue of an α-amino acid.

9 . A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 or a salt thereof.

10 . A compound selected from the group consisting of:

Assignments (2)
CONFIRMATORY LICENSE Recorded Jul 26, 2023
From: WASHINGTON UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064388/0583 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 17, 2021
From: JANETKA, JAMES W.; DAMALANKA, VISHNU
To: WASHINGTON UNIVERSITY
Reel/Frame 058413/0472 →
Continuity (3)
Provisional Application 63031340 · May 28, 2020
Provisional Application 62866069 · Jun 25, 2019
Related Publication 20220380407A1 · Dec 1, 2022
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