Tricyclic Amino Containing Compounds for Treatment or Prevention of Symptoms Associated with Endocrine Dysfunction

Abstract

The disclosure provides methods of use of certain compounds that are useful for treating certain symptoms of endocrine disturbances, and in particular those associated with hot flashes.

What is claimed: 
     
         1 . A method of treating or preventing hot flashes comprising administering a pharmaceutical composition comprising a compound of Formula I, 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, ester or prodrug thereof to a subject in need thereof wherein
 each K is independently N or CH; 
 Q, T, U, V, W, X, Y and Z are independently selected from H, R, acyl, F, Cl, Br, I, OH, OR, NH 2 , NHR, NR 2 , SR, SR, S 2 R, S—NHR, S 2 —NHR, S—NRR′, S 2 —NRR′, NHacyl, N(acyl) 2 , CO 2 H, CO 2 R, 
 R and R′ are independently selected from straight chain, branched or cyclic alkyl or aralkyl groups, as well as aryl and heteroaryl groups; and 
 R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are independently selected from H, straight chain, branched or cyclic alkyl, aralkyl, aryl heteroaryl, acyl and imidoyl. 
 
       
     
     
         2 . The method of  claim 1 , wherein the subject is menopausal or perimenopausal woman. 
     
     
         3 . The method of  claim 1 , wherein the subject is menstruating or expecting to menstruate with a week. 
     
     
         4 . The method of  claim 1 , wherein the subject is a woman diagnosed with vulvodynia. 
     
     
         5 . The method of  claim 1 , wherein the pharmaceutical composition is administered in combination with another active agent. 
     
     
         6 . The method of  claim 1 , wherein the pharmaceutical composition is administered in combination with an agonist or antagonist of an estrogen receptor. 
     
     
         7 . The method of  claim 1 , wherein the pharmaceutical composition is administered in combination with tamoxifen. 
     
     
         8 . The method of  claim 1 , wherein the pharmaceutical composition is administered in combination with an antiandrogen. 
     
     
         9 . The method of  claim 1 , wherein the subject is a man with prostate cancer. 
     
     
         10 . The method of claim, wherein the pharmaceutical composition is administered in combination with spironolactone, cyproterone, flutamide, nilutamide, bicalutamide, finasteride, or dutasteride. 
     
     
         11 . The method of  claim 1 , wherein said compound is N-(4-((pyrimidin-2-ylamino)methyl)benzyl)-pyrimidin-2-amine or pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 1 , further comprising the step of administering the pharmaceutical composition to the subject after, before, or during a surgery selected from a hysterectomy, oophorectomy, partial oophorectomy, unilateral salpingo-oophorectomy, bilaterial salpingo-oophorectomy or combination thereof. 
     
     
         13 . The use of a compound of  claim 1  in the production of a medicament for the treatment or prevention of hot flashes.