Beta adrenergic agonist and methods of using the same

Abstract

The present disclosure is directed to chemical compounds and to the use of such compounds in the treatment of diseases associated with an adrenergic receptor.

What is claimed is: 
     
         1 . A compound according to Formula (I′): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         A′, B′, and X′ are each independently nitrogen or carbon; 
         each R 1′  is independently halogen, —R′, —CN, —NO 2 , —SF 5 , —OR x , —NR x   2 , —NHR x , —SO 2 R′, —C(O)R′, —C(O)NR′ 2 ; 
         each R′ is independently hydrogen or an optionally substituted group selected from: C 1-6  aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic partially unsaturated or aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic partially unsaturated or heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; 
         each R x  is independently an optionally substituted group selected from: C 1-6  aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic partially unsaturated or aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic partially unsaturated or heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; 
         m′ is an integer selected from 0 to 4; 
         R 2′ , R 3′ , and R 4′  are each independently halogen, —R′, —CN, —NO 2 , —OR′, —NR′ 2 , 
       
       
         
           
           
               
               
           
         
         R 2′  and R 3′  together with the carbon form an optionally substituted 3-7 membered saturated carbocyclic ring; an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an optionally substituted 3-7 membered saturated or a partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 
         L′ is optionally substituted Ci-s alkylene; 
         Y 1′ , Y 2′ , Y 3′ , and Y 4′  are each independently a covalent bond, a carbon, an oxygen, or a nitrogen, optionally substituted with hydrogen, an optionally substituted C 1-6  alkyl, or an optionally substituted 3-7 membered saturated carbocyclic ring; 
         Z′ is O or S; 
         R 5′  and R 6′  are each independently hydrogen or optionally substituted alkyl, or 
         R 5′  and R 6′  are cyclically linked and, together with Y 2′ , to form an optionally substituted 3-7 membered saturated carbocyclic ring; an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an optionally substituted 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 
         each R 7′  is independently —R′, halogen, —CN, —NO 2 , —NR′ 2 , or —OR′; 
         n′ is an integer selected from 0 to 4; 
         R 8′  is hydrogen, —CN, optionally substituted alkyl, or an optionally substituted aryl ring; and 
         each R 9′  is independently hydrogen, halogen, —CN, —OR′, —NR′ 2 , or optionally substituted alkyl; and 
         R 10′  and R 11′  are each independently hydrogen or optionally substituted C 1-2  aliphatic. 
       
     
     
         2 . A compound according to Formula (II′): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         A′, B′, and X′ are each independently nitrogen or carbon; 
         each R 1′  is independently halogen, —R′, —CN, —NO 2 , —SF 5 , —OR x , —NR x   2 , —NHR x , —SO 2 R′, —C(O)R′, —C(O)NR′ 2 ; 
         each R′ is independently hydrogen or an optionally substituted group selected from: C 1-6  aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic partially unsaturated or aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic partially unsaturated or heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; 
         each R x  is independently an optionally substituted group selected from: C 1-6  aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic partially unsaturated or aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic partially unsaturated or heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; 
         m′ is an integer selected from 0 to 4; 
         R 2′ , R 3′ , and R 4′  are each independently halogen, —R′, —CN, —NO 2 , —OR′, —NR′ 2 , 
       
       
         
           
           
               
               
           
         
       
       or
 R 2′  and R 3′  together with the carbon form an optionally substituted 3-7 membered saturated carbocyclic ring; an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an optionally substituted 3-7 membered saturated or a partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 
 L′ is optionally substituted Ci-s alkylene; 
 Y 1′ , Y 2′  Y 3′ , and Y 4′  are each independently a covalent bond, a carbon, an oxygen, or a nitrogen, optionally substituted with hydrogen, an optionally substituted C 1-6  alkyl, or an optionally substituted 3-7 membered saturated carbocyclic ring; 
 Z′ is O or S; 
 R 5′  and R 6′  are each independently hydrogen or optionally substituted alkyl, or 
 R 5′  and R 6′  are cyclically linked and, together with Y 2′ , to form an optionally substituted 3-7 membered saturated carbocyclic ring; an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an optionally substituted 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 
 each R 7′  is independently —R′, halogen, —CN, —NO 2 , —NR′ 2 , or —OR′; 
 n′ is an integer selected from 0 to 4; 
 R 8′  is hydrogen, —CN, optionally substituted alkyl, or an optionally substituted aryl ring; and 
 each R 9′  is independently hydrogen, halogen, —CN, —OR′, —NR′ 2 , or optionally substituted alkyl.3. 
 
     
     
         3 . The compound according to any one of  claims 1 - 2 , wherein R 1′  is halogen, —CN, or an optionally substituted C 1-6  aliphatic. 
     
     
         4 . The compound according to any one of  claims 1 - 2 , wherein R 1′  is —CN. 
     
     
         5 . The compound according to any one of  claims 1 - 2 , wherein R 1′  is an optionally substituted C 1-6  aliphatic. 
     
     
         6 . The compound according to any one of  claims 1 - 2 , wherein R 1′  is methyl. 
     
     
         7 . The compound according to any one of  claims 1 - 2 , wherein R 1′  is —CF 3 . 
     
     
         8 . A pharmaceutical composition comprising the compound according to any one of  claims 1 - 2 .