Spiro-lactam compounds, process and uses thereof

Abstract

The present disclosure relates to a new class of antimicrobial agents. In particular, this disclosure provides the identification and characterization of novel spiro-lactam compounds as anti-HIV/AIDS and anti-malarial agents. Furthermore, this disclosure also provides the preparation of spiro-β-penicillanic acids, which proved to be potent inhibitors of HIV.

1 - 31 . (canceled) 
     
     
         32 . A method of treating a patient infected with one or more infectious diseases, the method comprising:
 administering a composition to the patient, wherein the composition comprises   a therapeutically effective amount of one of the following compounds:   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         33 . The method of  claim 32 , wherein the infectious diseases are caused by pathogenic agents selected from a virus, a protozoan, and mixtures thereof. 
     
     
         34 . The method of  claim 32 , wherein the infectious diseases are selected from acquired immunodeficiency syndrome, malaria, hepatitis A, hepatitis B, hepatitis C, hepatitis D or hepatitis E, herpes simplex infection, human papillomavirus infection, and respiratory infections caused by viruses. 
     
     
         35 . The method of  claim 32 , wherein the infectious disease is caused by an agent selected from: human immunodeficiency virus, human immunodeficiency virus-2 group A, human immunodeficiency virus-2 group B, human immunodeficiency virus-1 group M, human immunodeficiency virus-1 group O, human immunodeficiency virus-1 group N, human immunodeficiency virus-1 group P, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, herpes simplex virus 1, herpes simplex virus 2, human filovirus, togavirus, alphavirus, arenavirus, bunyavirus, flavivirus, human papillomavirus, human influenza A and B viruses, Asian flu virus, herpes zoster, severe acute respiratory syndrome coronaviruses, Respiratory Syncytial virus type A and B, and  Plasmodium  spp. 
     
     
         36 . The method of  claim 32 , wherein the infectious disease is a human immunodeficiency virus infection or  Plasmodium  spp. infection. 
     
     
         37 . The method of  claim 32 , wherein the patient is co-infected with HIV and  Plasmodium , and wherein the compound exhibits inhibitory activity against human immunodeficiency virus (HIV) and  Plasmodium  species. 
     
     
         38 . The method of  claim 33 , wherein the infectious disease is caused by a virus, and wherein the virus is human immunodeficiency virus-2 group A, human immunodeficiency virus-2 group B, human immunodeficiency virus-1 group M, human immunodeficiency virus-1 group O, human immunodeficiency virus-1 group N, or human immunodeficiency virus-1 group P. 
     
     
         39 . The method of  claim 33 , wherein the infectious disease is caused by a protozoan, and wherein the protozoan is a  Plasmodium  species selected from the group consisting of:  Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, Plasmodium malariae , and  Plasmodium knowlesi.    
     
     
         40 . The method of  claim 32 , wherein the composition administered to the patient further comprises an additional active ingredient, wherein the additional active ingredient is a HIV protease inhibitor (PI), a HIV nucleoside reverse transcriptase inhibitor (NRTI), a HIV non-nucleoside reverse transcriptase inhibitor (NNRTI), a HIV integrase inhibitor, a HIV entry inhibitor, or mixtures thereof. 
     
     
         41 . The method of  claim 32 , wherein the composition administered to the patient further comprises an antiviral agent, an anti-malarial agent, an immunomodulator agent, an analgesic agent, an anti-inflammatory agent, an antibiotic agent or a diuretic agent.