Polycyclic compounds and methods related thereto

Abstract

The invention relates to a novel compound of the formula or pharmaceutically acceptable salts thereof as well as pharmaceutical, nutraceutical, and botanical drug compositions and therapeutic methods related thereto. In certain embodiments, the compounds are used for the treatment of abnormal cell growth, hyperproliferative disorders, and inflammatory diseases in mammals. In other embodiments, the invention encompasses methods to isolate and synthesize the compounds.

What is claimed is: 
     
         1 . A method for the treatment of cancer in a mammal comprising administering to said mammal a pharmaceutically effective amount of a compound of the formula I or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein:
 X is a divalent moiety selected from: —O—; —S(O)—; —N(R y )—; —CH 2 O—; —OCH 2 —; —C(O)O—; —OC(O)—; —CH 2 N(R y )—; —C(O)N(R y )—; —N(R y )CH 2 —; —NR y C(O)—; and —(CR y ) 2 —; 
 Y is a divalent moiety selected from: —O—; —S(O)—; —N(R y )—; —CH 2 O—; —OCH 2 —; —C(O)(O)—, —OC(O)—; —CH 2 N(R y )—; —C(O)N(R y )—, —N(R y )CH 2 —; —NR y C(O)—; and —C(R y ) 2 —; 
 Z is selected from: ═C(R 4 ) 2 ; ═O; ═NR y ; ═NOR z ; ═NN(R y ) 2 ;
 —N(R y ) 2 ; —OR z ; —S(O) X R y ; C 1-20  aliphatic; C 1-20  heteroaliphatic having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; 6- to 14-membered aryl; 5- to 14-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and 4-7-membered heterocyclic having 1-3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur; 
 
 each R 1 , may be the same or different, each R 2  may be the same or different, and each R 3  may be the same or different and, at each occurrence are independently halogen; CN; —S(O) x R y —; —NR y C(O)R y ; —OC(O)R y ; —CO 2 R y ; NCO; —N 3 , OR z ; —OC(O)N(R y ) 2 ; N(R y ) 2 ; —NR y C(O)R y  and —NR y C(O)OR y ; or an optionally substituted group selected from the group consisting of C 1-20  aliphatic; C 1-20  heteroaliphatic having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur; 6-14-membered aryl; 5 to 14 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur and 4- to 7-membered heterocyclic having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, where two or more adjacent R 1 , R 2  and R 3  groups can be taken together with any intervening atoms to form an optionally substituted saturated, partially unsaturated or aromatic 5 to 12 membered ring containing 0 to 4 heteroatoms; and where two R 1 , R 2  or R 3  groups attached to the same carbon may be taken together to form a moiety selected from ═O, ═NOR Z , ═NN(R y ) 2 , ═C(R y ) 2  and an optionally substituted saturated, partially unsaturated 3-8 membered spirocyclic ring containing 0 to 4 heteroatoms selected from nitrogen, oxygen and sulfur; 
 R 4  is, at each occurrence, independently selected from: hydrogen; or an optionally substituted moiety selected from C 1-20  aliphatic; C 1-20  heteroaliphatic having 1-4 heteroatoms; 6- to 14-membered aryl; 5- to 10-membered heteroaryl; and 4- to 7-membered heterocyclic, where two R 4  groups may be taken together to form a moiety selected from the group consisting of: ═O; ═NOR z ; ═NN(R y ) 2 ; ═C(R y ) 2 ; and an optionally substituted saturated or partially unsaturated 3- to 8-membered spirocyclic ring containing 0 to 4 heteroatoms, 
 R y  is at each occurrence, independently selected from the group consisting of: hydrogen and an optionally substituted C 1-12  aliphatic group, 
 R z  is at each occurrence, independently selected from: hydrogen, an optionally substituted C 1-12  aliphatic, an optionally substituted C 2-20  acyl group, 
 
       
         
           
           
               
               
           
         
         R X  is hydrogen or an optionally substituted moiety selected from C 1-20  aliphatic; C 1-20  heteroaliphatic having 1-4 heteroatoms; 6- to 14-membered aryl; 5- to 10-membered heteroaryl; and 4- to 7-membered heterocyclic; 
         x is 0, 1, or 2, 
         a is 0, 1, 2, 3, 4, or 5, 
         b is 0, 1, 2, 3, 4, 5, 6, 7, or 8, 
         c is 0, 1, 2, 3, 4, 5, or 6, and 
            represents an optionally substituted bond that is either a single bond or a double bond.