JPWO2021211919A5 - - Google Patents

Claims (22)

A RIPK1 inhibitor comprising (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide, and/or a pharma- ceutically acceptable salt, tautomer, stereoisomer or mixture of stereoisomers thereof, for use in treating a subject at risk for or having cytokine release syndrome (CRS) or systemic inflammatory response syndrome (SIRS). A RIPK1 inhibitor comprising (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide, and/or a pharma- ceutically acceptable salt, tautomer, stereoisomer or mixture of stereoisomers thereof, for use in treating a subject having a hyperinflammatory condition. A RIPK1 inhibitor comprising (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide, and/or a pharma- ceutically acceptable salt, tautomer, stereoisomer or mixture of stereoisomers thereof, for use in reducing inflammation or organ damage in a subject at risk for or having cytokine release syndrome (CRS) or systemic inflammatory response syndrome (SIRS). A RIPK1 inhibitor comprising (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide, and/or a pharma- ceutically acceptable salt, tautomer, stereoisomer or mixture of stereoisomers thereof, for use in reducing symptoms associated with a viral infection in a subject in need thereof. The RIPK1 inhibitor according to claim 4, wherein the viral infection is caused by COVID-19/2019-nCoV/SARS-CoV-2, SARS-CoV, and/or MERS-CoV. The RIPK1 inhibitor for use according to any one of claims 1 to 5, wherein the RIPK1 inhibitor is (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide, and/or a pharma- ceutically acceptable salt thereof. The RIPK1 inhibitor for use according to any one of claims 1 to 5, wherein a dose of about 5 mg to about 1000 mg of the RIPK1 inhibitor is administered. The RIPK1 inhibitor for use according to claim 7, wherein the dose is 400 mg. The RIPK1 inhibitor for use according to claim 7, wherein the dose is 600 mg. The RIPK1 inhibitor for use according to claim 7, wherein the dose is 800 mg. The RIPK1 inhibitor for use according to claim 7, wherein the dose is 1000 mg. The RIPK1 inhibitor for use according to claim 7, wherein the RIPK1 inhibitor is administered daily. The RIPK1 inhibitor for use according to claim 7, wherein the RIPK1 inhibitor is administered in conjunction with antiviral therapy. The RIPK1 inhibitor for use according to claim 13, wherein the antiviral therapy is selected from remdesivir, hydroxychloroquine, galidesivir, oseltamivir, paramivir, zanamivir, ganciclovir, acyclovir, ribavirin, lopinavir, ritonavir, favipiravir, darunavir and combinations thereof. The RIPK1 inhibitor for use according to claim 7, wherein the RIPK1 inhibitor is administered in conjunction with corticosteroid treatment. The RIPK1 inhibitor for use according to claim 15, wherein the corticosteroid treatment is selected from dexamethasone, betamethasone, prednisone, prednisolone, methylprednisolone, cortisone, hydrocortisone, triamcinolone, ethametasone and combinations thereof. The RIPK1 inhibitor for use according to claim 7, wherein the RIPK1 inhibitor is administered orally. The RIPK1 inhibitor for use according to claim 7, wherein the RIPK1 inhibitor is administered via a gastric feeding tube. The RIPK1 inhibitor for use according to any one of claims 1 to 5, wherein the condition of the subject includes a systemic hyperinflammatory response. The RIPK1 inhibitor for use according to claim 19, wherein the systemic hyperinflammatory response is indicated by an increase in CRP, a decrease in white blood cell count, a change in neutrophil count, a decrease in neutrophil to lymphocyte ratio, and/or an increase in IL-6. The RIPK1 inhibitor for use according to any one of claims 1 to 5, wherein the subject's condition exhibits innate immune activation. The RIPK1 inhibitor for use according to claim 21, wherein innate immune activation is indicated by an increase in CRP, a change in neutrophil count, and/or an increase in IL-6.