New use of angiotensin ii type 2 receptor agonist

Abstract

There is provided N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutyl-thiophene-2-sulfonamide, or a pharmaceutically-acceptable salt thereof, for use in a method of treatment of respiratory virus-induced tissue damage. Such damage may be caused by coronaviruses, including severe acute respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus. N-Butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide alleviate symptoms of diseases caused by those viruses (including coronavirus disease 2019 or COVID-19), such as cough, dyspnea, pneumonia, respiratory distress, respiratory failure and/or fibrosis of organs such as the lungs, the heart or the kidneys, and may thus prevent respiratory virus-induced morbidity and/or mortality. In particular, it has been found in a clinical study that the proportion of patients with COVID-19 needing oxygen treatment was significantly lower for patients that were administered N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide compared to placebo.

1 . A method of treatment of respiratory virus-induced tissue damage in a subject, which method comprises administering N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide, or a pharmaceutically-acceptable salt thereof, to a subject in need of such treatment. 
     
     
         2 . A method of treatment as claimed in  claim 1 , wherein the tissue is lung tissue. 
     
     
         3 . A method of treatment as claimed in  claim 1 , wherein the tissue is the respiratory epithelium. 
     
     
         4 . A method as claimed in  claim 1 , wherein the respiratory virus is a coronavirus. 
     
     
         5 . A method, as claimed in  claim 1 , wherein the virus is severe acute respiratory syndrome coronavirus or severe acute respiratory syndrome coronavirus 2. 
     
     
         6 . A method as claimed in  claim 5 , wherein the treatment of respiratory tissue damage includes treatment of a disease that is being, or has been, caused by the virus. 
     
     
         7 . A method as claimed in  claim 6 , wherein the disease is a severe acute respiratory syndrome. 
     
     
         8 . A method as claimed in  claim 6 , wherein the disease is coronavirus disease 2019. 
     
     
         9 . A method as claimed in  claim 5 , wherein the treatment includes treatment of the symptoms of the disease that is being, or has been, caused by the virus. 
     
     
         10 . A method as claimed in  claim 9 , wherein the symptoms of the damage or the disease include one or more of cough, dyspnea, respiratory distress and/or respiratory failure. 
     
     
         11 . A method as claimed in  claim 9 , wherein the symptoms of the damage or the disease include one or more of pneumonia and/or fibrosis in one or more internal organs. 
     
     
         12 . A method as claimed in  claim 11 , wherein the one or more internal organs are selected from the lungs, the heart and/or the kidneys. 
     
     
         13 . A method as claimed in  claim 1 , wherein the treatment includes prevention of respiratory virus-induced morbidity and/or mortality. 
     
     
         14 . A method as claimed in  claim 1 , wherein the salt is a sodium salt. 
     
     
         15 . A pharmaceutical formulation including N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide, or a pharmaceutically-acceptable salt thereof; a therapeutic agent that is useful in the treatment of a viral infection; and a pharmaceutically-acceptable adjuvant, diluent or carrier. 
     
     
         16 . A kit of parts comprising components:
 (A) a pharmaceutical formulation including N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide, or a pharmaceutically-acceptable salt thereof, in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier; and   (B) a pharmaceutical formulation including a therapeutic agent that is useful in the treatment of a viral infection, in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier,   
       which components (A) and (B) are each provided in a form that is suitable for administration in conjunction with the other. 
     
     
         17 . A kit of parts as claimed in  claim 16 , wherein the therapeutic agent that is useful in the treatment of a viral infection is selected from the group: antiviral agents, non-steroidal antiinflammatory agents, analgesics, antitussive agents, passive antibody therapies, antifibrotics, vitamins, mucolytics, corticosteroids, H2 receptor blockers, anticoagulants, anti-platelet drugs, statins, antimicrobial agents and anti-allergic/anti-asthmatic drugs. 
     
     
         18 . A kit of parts as claimed in  claim 16 , wherein the therapeutic agent that is useful in the treatment of a viral infection is selected from the group: oseltamivir, remdesivir, favilavir, simeprevir, daclatasvir, sofosbuvir, ribavirin, umifenovir, lopinavir, ritonavir, teicoplanin, camostat, Actembra, TZLS-501, AT-100 (rhSP-D), OYA1, BPI-002, ifenprodil, galidesivir, REGN3048-3051, kevzara, ibuprofen, ketorolac, naproxen, chloroquine, hydroxychloroquine, interferon beta, interferon beta-1a, tocilizumab, lenalidomide, pomalidomide, thalidomide, paracetamol, an opioid, dextromethorphan, nintedanib, pirfenidone), vitamin B, vitamin C, vitamin D), acetylcysteine, ambroxol, cortisol (hydrocortisone), aldosterone, corticosterone, cortisone, pregnenolone, progesterone, 11-deoxycortisol, 21-deoxycortisol, 11-dehydrocorticosterone, 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone, 18-hydroxycorticosterone, 21-deoxycortisone, 11β-hydroxypregnenolone, 11β,17α,21-trihydroxypregnenolone, 17α,21-dihydroxypregnenolone, 17α-hydroxypregnenolone, 21-hydroxypregnenolone, 11-ketoprogesterone, 11β-hydroxyprogesterone, 17α-hydroxyprogesterone, 18-hydroxyprogesterone, cortisone acetate, hydrocortisone aceponate, hydrocortisone acetate, hydrocortisone buteprate, hydrocortisone butyrate, hydrocortisone valerate, tixocortol and tixocortol pivalate, prednisolone, methylprednisolone, prednisone, chloroprednisone, cloprednol, difluprednate, fludrocortisone, fluocinolone, fluperolone, fluprednisolone, loteprednol, prednicarbate, triamcinolone, amcinonide, budesonide, desonide, fluocinolone cetonide, fluocinonide, halcinonide, triamcinolone acetonide, ciclesonide, deflazacort, formocortal, fludroxycortide, flunisolide, fluocinolone acetonide, beclomethasone, betamethasone, betamethasone dipropionate, betamethasone valerate, dexamethasone, fluocortolone, halometasone, mometasone, mometasone furoate, alclometasone, alclometasone dipropionate, clobetasol, clocortolone, desoximetasone, diflorasone, difluocortolone, fluclorolone, flumetasone, fluocortin, fluprednidene, fluticasone, meprednisone, paramethasone, prednylidene, rimexolone, ulobetasol, flugestone, fluorometholone, medrysone, prebediolone acetate, chlormadinone acetate, cyproterone acetate, medrogestone, medroxyprogesterone acetate, megestrol acetate and segesterone acetate, cortivazol, 6-methyl-11β,17β-dihydroxy-17α-(1-propynyl)androsta-1,4,6-trien-3-one, famotidine, bemiparin, nadroparin, reviparin, enoxaparin, parnaparin, certoparin, dalteparin, tinzaparin, dabigatran, argatroban, rivaroxaban, apixaban, edoxaban, betrixaban, darexaban, otamixaban, letaxaban, eribaxaban, hirudin, lepirudin, coumarin, acenocoumarol, phenprocoumon, atromentin, fondaparinux, idraparinux, idrabiotaparinux, triflusal, cangrelor, clopidogrel, prasugrel, ticagrelor, ticlopidine, cilostazol, vorapaxar, abciximab, eptifibatide, tirofiban, dipyridamole, terutroban, ramatroban, seratrodast, picotamide, atorvastatin, simvastatin, rosuvastatin, azithromycin, ceftriaxone, cefuroxime, doxycycline, fluconazole, piperacillin, tazobactam, teicoplanin, chlorphenamine, levocetirizine and montelukast. 
     
     
         19 . A kit of parts as claimed in  claim 16 , wherein the therapeutic agent is selected from prednisolone, methylprednisolone, dexamethasone, remdesivir, interferon beta and interferon beta-1a.