Substituted bisphenylalkylurea compounds and methods of treating inflammatory conditions

Abstract

Disclosed is a composition and method for a therapeutic treatment that is able to combat triple negative breast cancers (TNBCs). The class of urea compounds acts by blocking at inhibiting the mTOR signaling pathway, which, as a central regulator of mammalian metabolism and physiology that when inhibited leads to the induction of autophagocytosis. The disclosed compounds are further capable of reinitiating the p53 cycle as well as inhibition of the BNIP3/BNIP3L pathway. The disclosed compounds also shows the ability to cross the blood-brain-barrier where metastases can form. This new drug has the potential to be a powerful new treatment to combat invasive TNBCs.

1 - 22 . (canceled) 
     
     
         23 . A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein: 
         R1 is selected from a group consisting of hydrogen, hydroxy, alkyloxy, halogen, haloalkoxy, alkyl ester, amine, alkylamine, dialkylamine, thio, thioalkyl, and alkyl ethers; 
         R4-R5 are independently selected from a group consisting of trifluoromethyl radical (CF 3 ), nitro (NO 2 ), hydrogen, halogen, alkyl, alkyl ester, and amine; and 
         n is an integer number representing a repeating unit of the compound. 
       
     
     
         24 . The compound of  claim 23 , wherein R1 is a halogen and the halogen is fluorine (F). 
     
     
         25 . The compound of  claim 24 , wherein R4 is nitro (NO 2 ) and R5 is trifluoromethyl radical (CF 3 ). 
     
     
         26 . The compound of  claim 24 , wherein R5 is nitro (NO 2 ). 
     
     
         27 . The compound of  claim 26 , wherein R4 is trifluoromethyl radical (CF 3 ). 
     
     
         28 . The compound of  claim 23 , wherein the compound reduces inflammation to treat a disease causing inflammation in a patient. 
     
     
         29 . The compound of  claim 23 , wherein the compound reduces neuroinflammation by inhibiting H1 and H2 receptors in a patient. 
     
     
         30 . The compound of  claim 23 , wherein the compound comprises an aqueous solution and one or more pharmaceutically acceptable excipients, additives, carriers or adjuvants. 
     
     
         31 . The compound of  claim 23 , wherein the compound further comprises one or more excipients, carriers, additives, adjuvants, or binders in a tablet or capsule. 
     
     
         32 . A method for of treating an inflammatory disease in a mammal comprising the step of: administering to a patient a pharmaceutical acceptable amount of a compound being a bisphenylalkylurea compound selected from a group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         33 . The method of  claim 32 , wherein the compound further comprises one or more excipients, carriers, additives, adjuvants, or binders in a tablet or capsule. 
     
     
         34 . The method of  claim 32  further comprising administering the compound via an oral, intraperitoneal, intravascular, peripheral circulation, subcutaneous, intraorbital, ophthalmic, intraspinal, intracisternal, topical, infusion, implant, aerosol, inhalation, scarification, intracapsular, intramuscular, intranasal, buccal, transdermal, pulmonary, rectal, or vaginal route. 
     
     
         35 . The method of of  claim 32  further comprising:
 reducing neuroinflammation to treat the inflammatory disease causing neuroinflammation in the patient. 
 
     
     
         36 . The compound of  claim 32 , wherein the reducing neuroinflammation occurs as result of the compound inhibiting H1 and H2 receptors in the patient. 
     
     
         37 . A method for treating an inflammatory disease in a mammal comprising the step of: administering to a patient a pharmaceutical acceptable amount of a compound being a bisphenylalkylurea compound: 
       
         
           
           
               
               
           
         
         wherein R1, R4, and R5 are independent functional groups each comprising one or more chemical elements, and 
         n is an integer number representing a repeating unit of the compound. 
       
     
     
         38 . The method of  claim 37 , wherein R1 is selected from a group consisting of hydrogen, hydroxy, alkyloxy, halogen, haloalkoxy, alkyl ester, amine, alkylamine, dialkylamine, thio, thioalkyl, alkyl ethers; and R4-R5 are independently selected from a group consisting of trifluoromethyl radical (CF 3 ), nitro (NO 2 ), hydrogen, halogen, alkyl, alkyl ester, and amine. 
     
     
         39 . The method of  claim 37 , wherein the bisphenylalkylurea compound is selected from a group consisting of Formula I, Formula II, Formula III, Formula IV Formula V, Formula VI Formula VII, Formula VIII Formula IX, Formula X and Formula XI. 
     
     
         40 . The method of  claim 37  further comprising administering the compound via an oral, intraperitoneal, intravascular, peripheral circulation, subcutaneous, intraorbital, ophthalmic, intraspinal, intracisternal, topical, infusion, implant, aerosol, inhalation, scarification, intracapsular, intramuscular, intranasal, buccal, transdermal, pulmonary, rectal, or vaginal route. 
     
     
         41 . The method of of  claim 37  further comprising:
 reducing neuroinflammation to treat the neuroinflammatory disease causing neuroinflammation in the patient. 
 
     
     
         42 . The compound of  claim 41 , wherein the reducing neuroinflammation occurs as result of the compound inhibiting H1 and H2 receptors in the patient. 
     
     
         43 . A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein: 
         X is selected from a group consisting of carbon and nitrogen; 
         R1 is selected from a group consisting of hydrogen, hydroxy, alkyloxy, halogen, haloalkoxy, alkyl ester, amine, alkylamine, dialkylamine, thio, thioalkyl, and alkyl ethers; 
         R4-R5 are independently selected from a group consisting of trifluoromethyl radical (CF 3 ), nitro (NO 2 ), hydrogen, halogen, alkyl, alkyl ester, and amine; and 
         n is an integer number representing a repeating unit of the compound. 
       
     
     
         44 . The compound of  claim 43 , wherein X is carbon. 
     
     
         45 . The compound of  claim 44 , wherein the compound reduces inflammation to treat a disease causing inflammation in a patient. 
     
     
         46 . The compound of  claim 44 , wherein the compound reduces neuroinflammation by inhibiting H1 and H2 receptors in a patient. 
     
     
         47 . The compound of  claim 43 , wherein X is nitrogen. 
     
     
         48 . The compound of  claim 43 , wherein R1 is a halogen and the halogen is fluorine (F). 
     
     
         49 . The compound of  claim 43 , wherein R4 is a halogen and R5 is trifluoromethyl radical (CF 3 ). 
     
     
         50 . The compound of  claim 49 , wherein R4 is chlorine (Cl). 
     
     
         51 . The compound of  claim 43 , wherein R4 is a halogen and the halogen is chlorine (Cl). 
     
     
         52 . The compound of  claim 43 , wherein the compound reduces neuroinflammation to treat a disease causing neuroinflammation in a patient. 
     
     
         53 . The compound of  claim 43 , wherein the compound reduces neuroinflammation by inhibiting H1 and H2 receptors in a patient. 
     
     
         54 . The compound of  claim 43 , wherein the compound reduces neuroinflammation by inhibiting H1 and H2 receptors in a patient. 
     
     
         55 . The compound of  claim 43 , wherein the compound comprises an aqueous solution and one or more pharmaceutically acceptable excipients, additives, carriers or adjuvants. 
     
     
         56 . The compound of  claim 43 , wherein the compound further comprises one or more excipients, carriers, additives, adjuvants, or binders in a tablet or capsule. 
     
     
         57 . A method for treating an inflammatory disease in a mammal comprising the step of: administering to a patient a pharmaceutical acceptable amount of a compound being a bisphenylalkylurea compound: 
       
         
           
           
               
               
           
         
         wherein X, R1, R4, and R5 are independent functional groups each comprising one or more chemical elements, and 
         n is an integer number representing a repeating unit of the compound. 
       
     
     
         58 . The method of  claim 57 , wherein X is nitrogen; R1 is a halogen; and R4-R5 are independently selected from a group consisting of trifluoromethyl radical (CF 3 ), hydrogen, halogen, alkyl, alkyl ester, and amine. 
     
     
         59 . The method of  claim 58 , wherein R1 is fluorine (F); R4 is a halogen; and R5 is a trifluoromethyl radical (CF 3 ). 
     
     
         60 . The method of  claim 57  further comprising administering the compound via an oral, intraperitoneal, intravascular, peripheral circulation, subcutaneous, intraorbital, ophthalmic, intraspinal, intracisternal, topical, infusion, implant, aerosol, inhalation, scarification, intracapsular, intramuscular, intranasal, buccal, transdermal, pulmonary, rectal, or vaginal route. 
     
     
         61 . The method of of  claim 57  further comprising:
 reducing neuroinflammation to treat the inflammatory disease causing neuroinflammation in the patient. 
 
     
     
         62 . The compound of  claim 61 , wherein the reducing neuroinflammation occurs as result of the compound inhibiting H1 and H2 receptors in the patient.