Methods of using [3.2.0] heterocyclic compounds and analogs thereof

Abstract

Disclosed are methods of treating cancer, inflammatory conditions, and/or infectious disease in an animal comprising: administering to the animal, a therapeutically effective amount of a heterocyclic compound. The animal is a mammal, preferably a human or a rodent.

1 . A method of treating a neoplastic disease in an animal, the method comprising: 
 administering to the animal, a therapeutically effective amount of a compound of a formula selected from Formulae I-V, and pharmaceutically acceptable salts and pro-drug esters thereof:    
     
     
         2 . The method of  claim 1 , wherein the neoplastic disease is cancer.  
     
     
         3 . The method of  claim 2 , wherein the cancer is selected from the group consisting of breast cancer, sarcoma, leukemia, ovarian cancer, uretal cancer, bladder cancer, prostate cancer, colon cancer, rectal cancer, stomach cancer, lung cancer, lymphoma, multiple myeloma, pancreatic cancer, liver cancer, kidney cancer, endocrine cancer, skin cancer, melanoma, angioma, and brain or central nervous system (CNS) cancer.  
     
     
         4 . The method of  claim 3 , wherein the cancer is a multiple myeloma, a colorectal carcinoma, a prostate carcinoma, a breast adenocarcinoma, a non-small cell lung carcinoma, an ovarian carcinoma or a melanoma.  
     
     
         5 . The method of  claim 2 , wherein the cancer is a drug resistant cancer.  
     
     
         6 . The method of  claim 5 , wherein the drug-resistant cancer displays at least one of the following: elevated levels of the P-glycoprotein efflux pump, increased expression of the multidrug-resistance associated protein 1 encoded by MRP1, reduced drug uptake, alteration of the drug's target or increasing repair of drug-induced DNA damage, alteration of the apoptotic pathway or the activation of cytochrome P450 enzymes.  
     
     
         7 . The method of  claim 5 , wherein the drug resistant cancer is a sarcoma or a leukemia.  
     
     
         8 . The method of  claim 1 , wherein the animal is a mammal.  
     
     
         9 . The method of  claim 1 , wherein the animal is a human.  
     
     
         10 . The method of  claim 1 , wherein the animal is a rodent.  
     
     
         11 . The method of  claim 1 , wherein the the compound is:  
       
         
           
           
               
               
           
         
         wherein R 8  is selected from the group consisting of H, F, Cl, Br and I.  
       
     
     
         12 . The method of  claim 1 , wherein the compound is:  
       
         
           
           
               
               
           
         
         wherein R 8  is selected from the group consisting of H, F, Cl, Br, and I.  
       
     
     
         13 . The method of  claim 1 , further comprising the steps of: 
 identifying a subject that would benefit from administration of an anticancer agent;    performing the method on the subject.    
     
     
         14 . A pharmaceutical composition comprising a compound of a formula selected from Formulae I-V, and pharmaceutically acceptable salts and pro-drug esters thereof.  
     
     
         15 . The pharmaceutical composition of  claim 14 , further comprising an anti-microbial agent.  
     
     
         16 . A method of inhibiting the growth of a cancer cell, comprising contacting a cancer cell with a compound of a formula selected from Formulae I-V, and pharmaceutically acceptable salts and pro-drug esters thereof.  
     
     
         17 . The method of  claim 16 , wherein the cancer cell is a multiple myeloma, a colorectal carcinoma, a prostate carcinoma, a breast adenocarcinoma, a non-small cell lung carcinoma, an ovarian carcinoma and a melanoma.  
     
     
         18 . A method of inhibiting proteasome activity comprising the step contacting a cell with a compound of a formula selected from Formulae I-V, and pharmaceutically acceptable salts and pro-drug esters thereof.  
     
     
         19 . A method of inhibiting NF-κB activation comprising the step contacting a cell with a compound of a formula selected from Formulae I-V, and pharmaceutically acceptable salts and pro-drug esters thereof.  
     
     
         20 . A method for treating an inflammatory condition, comprising administering an effective amount of a compound of a formula selected from Formulae I-V to a patient in need thereof.  
     
     
         21 . The method of  claim 20 , wherein the inflammatory condition is selected from the group consisting of rheumatoid arthritis, asthma, multiple sclerosis, psoriasis, stroke, and myocardial infarction.  
     
     
         22 . A method for treating a microbial illness comprising administering an effective amount of a compound of a formula selected from Formulae I-V to a patient in need thereof.  
     
     
         23 . The method of  claim 22 , wherein the microbial illness is caused by a microbe selected from the group consisting of  B. anthracis, Plasmodium, Leishmania,  and  Trypanosoma.