Aminoalkyl substituted 5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole and 5,6,7,8-tetrahydro-9H-pyrimidino[4,5-b]indole derivatives: CRF1 specific ligands

Abstract

Disclosed are compounds of the formula: wherein Ar, R 1 , W, X and m are substituents as defined herein. These compounds are modulators of CRF receptors and are therefore useful for treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of Formula I.

What is claimed is:  
     
         1 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       or the pharmaceutically acceptable salts thereof wherein: 
 Ar is phenyl, 1- or 2-naphthyl, 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, optionally mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, carboxamido, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, with the proviso that at least one of the positions ortho or para to the point of attachment of Ar to the tricyclic ring system is substituted;  
 R 1  is hydrogen, halogen, trifluoromethyl, C 1 -C 6  alkyl, or (C 1 -C 6  alkyl)-G 1 -R 2  where G 1  is oxygen or sulfur and R 2  is hydrogen or C 1 -C 6  alkyl;  
 W is N or C—R 3  where R 3  is hydrogen or C 1 -C 6  alkyl;  
 m is 0, 1, or 2;  
 X is  
                     
  wherein 
 V 1  and V 2  are CH 2 , CO, CS, SO 2  or CH(C 1 -C 6  alkyl), with the proviso that both V 1  and V 2  cannot both be CO, CS or SO 2 ;  
 Y 1  and Y 2  independently represent a bond or C 1 -C 6  alkylene;  
 A 1  is NR 4 R 5  wherein R 4  and R 5  are independently 
 hydrogen or a C 1 -C 6  alkyl group which and optionally forms a heterocycloalkyl group with Y 1 ;  
 acetyl or sulfonyl with the proviso that R 4  and R 5  cannot both be acetyl or sulfonyl; or  
 NR 4 R 5  taken together form a C 3 -C 6  heterocycloalkyl or a group of the formula:  
                     wherein e and f are independently 1, 2, or 3 and the sum of e and f is at least 3; and    G is     NR 6  wherein R 6  is hydrogen or C 1 -C 6  alkyl, or     CH(C 0 -C 6  alkylene)-G 3 -R 7  wherein G 3  is CONH, CONH(C 1 -C 6  alkyl), NH, NH(C 1 -C 6  alkyl) and R 7  is hydrogen or C 1 -C 6  alkyl; or     CONH 2 , CO[N(C 1 -C 6  alkyl)R 8 ] wherein R 8  is hydrogen or C 1 -C 6  alkyl;    
 
 A 2  is hydrogen, C 1 -C 6  alkyl, (C 1 -C 6  alkylene)-G 4 -R 9  wherein G 4  is oxygen or sulfur and R 9  is hydrogen, trifluoromethyl or C 1 -C 6  alkyl;  
                     wherein heteroaryl is 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono- or disubstituted with halogen, trifluoromethyl, amino, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, with the proviso that tetraazolinyl can have at most one substituent;    Z is C 1 -C 6  alkyl; and    V 2 , Y 2  and A 2  are as defined above;                           wherein 
 Z 2  is carbon or nitrogen;  
 wherein  
  when Z 2  is CH, n is 0, 1, 2 or 3 and p is 1, 2, or 3, R 10  is carboxamido, or (C 1 -C 6  alkylene)-G 5 -R 11  wherein G 5  is NH, NH(C 1 -C 6  alkyl) and R 11  is hydrogen or C 1 -C 6  alkyl;  
  when Z 2  is carbon, n is 1 or 2 and p is 1 or 2, R 10  is amino; or  
  when Z 2  is nitrogen, n is 1 or 2 and p is 1 or 2, R 10  is hydrogen; or  
 (iv) a nitrogen heterocycle of the formula:  
                     
  wherein the N-ring represents triazolyl, tetrazolyl, imidazolyl, pyrazolyl, each of which is optionally substituted with amino, trifluoromethyl, carboxamido, or (C 1 -C 6  alkylene)-G 6 -R 12  wherein G 6  is NH, NH(C 1 -C 6  alkyl) and R 12  is hydrogen or C 1 -C 6  alkyl.  
   
 
 
     
     
         2 . A compound according to  claim 1 , wherein V 1  and V 2  represent methylene; Y 1  is a bond; A 1  represents pyrrolidinyl, morpholinyl; piperazinyl, or mono- or di-C 1 -C 6  alkyl; Y 2  represents a bond or methylene; and A 2  represents C 1 -C 6  alkyl or C 1 -C 6  alkoxymethyl.  
     
     
         3 . A compound according to  claim 1 , wherein each R a  independently represents C 1 -C 6  alkyl; and A 2  is C 1 -C 6  cycloalkyl.  
     
     
         4 . A compound according to  claim 1 , where A 2  is (C 3 -C 5 ) cycloalkyl (C 1 -C 4 ) alkyl.  
     
     
         5 . A compound according to  claim 1 , where 
 A 1  is 
 NR 4 R 5  where R 4  and R 5  are independently hydrogen, C 1 -C 6  alkyl; or  
 NR 4 R 5  forms a 5 or 6-membered nitrogen heterocycle optionally containing an oxygen or second nitrogen atom;  
   Y 1  is C 1 -C 6  alkylene;    Y 2  is a bond or C 1 -C 6  alkylene;    V 1  is methylene; and V 2  is methylene.    
     
     
         6 . A compound according to  claim 5 , wherein A 2  is (C 3 -C 5 ) cycloalkyl.  
     
     
         7 . A compound according to  claim 6 , wherein R 4  and R 5  are independently C 1 -C 6  alkyl.  
     
     
         8 . A compound according to  claim 5 , wherein at least one R a  is methyl; Y 2  is a bond; and R 4  and R 5  are the same and represent C 1 -C 3  alkyl.  
     
     
         9 . A compound according to  claim 1 , wherein m is 1 and R 1  is C 1 -C 3  alkyl.  
     
     
         10 . A compound according to  claim 1 , which is  
       
         
           
           
               
               
           
         
         wherein X, m, and R 1  are as defined in  claim 1;  and each R a  is halogen, trifluoromethyl, hydroxy, amino, C 1 -C 6  alkyl, or C 1 -C 6  alkoxy.  
       
     
     
         11 . A compound according to  claim 10 , wherein V 1  and V 2  represent methylene; Y 1  is a bond; Al represents pyrrolidinyl, morpholinyl; piperazinyl, or mono- or di-C 1 -C 6  alkyl; Y 2  represents a bond or methylene; and A 2  represents C 1 -C 6  alkyl or C 1 C 6  alkoxymethyl.  
     
     
         12 . A compound according to  claim 10 , where 
 at least one R a  is C 1 -C 6  alkyl and the other R a  groups are independently C 1 -C 6  alkyl, halogen, C 1 -C 6  alkoxy or trifluoromethyl;    A 2  is (C 3 -C 5 )cycloalkyl(C 1 -C 4 )alkyl or (C 3 -C 4 )cycloalkyl;    A 1  is 
 NR 4 R 5  where R 4  and R 5  are independently hydrogen, C 1 -C 6  alkyl; or  
 NR 4 R 5  forms a 5 or 6-membered nitrogen heterocycle optionally containing an oxygen or second nitrogen atom;  
   Y 1  is C 1 -C 6  alkylene;    Y 2  is a bond or C 1 -C 6  alkylene;    V 1  is methylene; and V 2  is methylene.    
     
     
         13 . A compound according to  claim 10 , wherein A 2  is cyclopropyl(C 1 -C 3 )alkyl or (C 3 -C 5 )cycloalkyl; and R 4  and R 5  are independently C 1 -C 6  alkyl.  
     
     
         14 . A compound according to  claim 12 , wherein A 2  is (C 3 -C 5 )cycloalkyl; Y 2  is a bond; and R 4  and R 5  are the same and represent C 1 -C 3  alkyl.  
     
     
         15 . A compound according to  claim 12 , where each R a  is methyl; A 2  is cyclopropyl; Y 2  is a bond; and R 4  and R 5  are the same and represent C 1 -C 3  alkyl.  
     
     
         16 . A compound according to  claim 1 , which is  
       
         
           
           
               
               
           
         
         wherein X, m, and R 1  are as defined in  claim 1;  and each R a  is halogen, trifluoromethyl, hydroxy, amino, C 1 -C 6  alkyl, or C 1 -C 6  alkoxy.  
       
     
     
         17 . A compounds according to  claim 16 , wherein V 1  and V 2  represent methylene; Y 1  is a bond; A 1  represents pyrrolidinyl, morpholinyl; piperazinyl, or mono- or di-C 1 -C 6  alkyl; Y 2  represents a bond or methylene; and A 2  represents C 1 -C 6  alkyl or C 1 -C 6  alkoxymethyl.  
     
     
         18 . A compound according to  claim 16 , wherein each R a  independently represents C 1 -C 6  alkyl; 
 A 2  is (C 3 -C 5 )cycloalkyl(C 1 -C 4 )alkyl or (C 3 -C 5 )cycloalkyl;    A 1  is 
 NR 4 R 5  where R 4  and R 5  are independently hydrogen, C 1 -C 6  alkyl; or  
 NR 4 R 5  forms a 5 or 6-membered nitrogen heterocycle optionally containing an oxygen or second nitrogen atom;  
   Y 1  is C 1 -C 6  alkylene;    Y 2  is a bond or C 1 -C 6  alkylene; 
 V 1  is methylene; and V 2  is methylene.  
   
     
     
         19 . A compound according to  claim 16 , wherein A 2  is cyclopropyl(C 1 -C 3 )alkyl or (C 3 -C 5 )cycloalkyl; and R 4  and R 5  are independently C 1 -C 6  alkyl.  
     
     
         20 . A compound according to  claim 18 , wherein A 2  is (C 3 -C 5 )cycloalkyl; Y 2  is a bond; and R 4  and R 5  are the same and represent C 1 -C 3  alkyl.  
     
     
         21 . A compound according to  claim 18 , wherein at least one R a  is methyl; A 2  is (C 3 -C 5 ) cycloalkyl; Y 2  is a bond; and R 4  and R 5  are the same and represent C 1 -C 3  alkyl.  
     
     
         22 . A compound according to  claim 18 , wherein each R a  is methyl; A 2  is cyclopropyl; Y 2  is a bond; and R 4  and R 5  are the same and represent C 1 -C 3  alkyl.  
     
     
         23 . A compound according to  claim 18 , wherein m is 1.  
     
     
         24 . A compound according to  claim 16 , wherein m is 2.  
     
     
         25 . A compound according to  claim 21 , m is 1 and R 1  is C 1 -C 3  alkyl.  
     
     
         26 . A compound according to  claim 1  which is: 
 4-(N-(2-Pyrrolidinoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Morpholinoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-2-(4-Methylpiperazinyl)ethyl-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Dimethylaminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Pyrrolidinoethyl)-N-2-methylpropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Dimethylaminoethyl)-N-2-methylpropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-(Ethylmethylamino)ethyl)-N-2-methylpropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Dimethylaminoethyl)-N-2-methoxyethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Dimethylaminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyrimidino[4,5-b]indole; and  
 4-(N-(2-Pyrrolidinoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4-dimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole.  
 
     
     
         27 . A compound according to  claim 1  which is: 
 4-(N-(2-Pyrrolidinoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,6-dimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-(4-Triazolyl)ethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-(2-Methoxyethyl)aminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-(2-Methylimidazolinyl)ethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Dimethylaminoethyl)-N-isopropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-(Phenylmethyl)aminoethyl)-N-isopropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-2-(4-Methylpiperazinyl)ethyl-N-isopropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Pyrrolidinoethyl)-N-isopropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Diethylaminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole; and  
 4-(N-(2-Diethylaminoethyl)-N-2-methylpropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole.  
 
     
     
         28 . A compound according to  claim 1  which is: 
 4-(N-(2-Aminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Aminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,6-dimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Aminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole);  
 4-(N-(2-Aminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4-dimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole;  
 4-(N-(2-Dimethylaminoethyl)-N-butyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole; and  
 4-(N-(2-Dimethylaminoethyl)-N-propyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole.  
 
     
     
         29 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of  claim 1 .  
     
     
         30 . A method for the treatment or prevention of physiological disorders associated with an excess of CRF, which method comprises administration to a patient in need thereof a CRF-reducing amount of a compound according to  claim 1 .  
     
     
         31 . A salt according to  claim 1  which is: 
 4-(N-(2-Morpholinoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole citrate;  
 4-(N-2-(4-Methylpiperazinyl)ethyl-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole phosphate;  
 4-(N-(2-(2-Methoxyethyl)aminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole citrate;  
 4-(N-(2-Pyrrolidinoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride;  
 4-(N-(2-Dimethylaminoethyl)-N-2-methylpropyl)amino -2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole citrate;  
 4-(N-(2-Aminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;  
 4-(N-(2-(Ethylmethylamino)ethyl)-N-2-methylpropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride;  
 4-(N-(2-Pyrrolidinoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4-dimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;  
 4-(N-(2-(2-Methylimidazolinyl)ethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole fumarate;  
 4-(N-(2-Dimethylaminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride; and  
 4-(N-(2-Dimethylaminoethyl)-N-2-methoxyethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride.  
 
     
     
         32 . A salt according to  claim 1  which is: 
 4-(N-2-(4-Methylpiperazinyl)ethyl-N-isopropyl)amino -2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;  
 4-(N-(2-Diethylaminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;  
 4-(N-(2-Dimethylaminoethyl)-N-propyl)amino-2-methyl -9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole maleate;  
 4-(N-(2-Methylaminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;  
 4-(N-(2-(Phenylmethyl)aminoethyl)-N-isopropyl)amino -2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole phosphate;  
 4-(N-(2-Diethylaminoethyl)-N-2-methylpropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole acetate;  
 4-(N-(2-(Ethylmethylamino)ethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole fumarate;  
 4-(N-(2-Dimethylaminoethyl)-N-isopropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole phosphate;  
 4-(N-(2-Dimethylaminoethyl)-N-ethyl)amino-2-methyl -9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride; and  
 4-(N-(2-Dimethylaminoethyl)-N-butyl)amino-2-methyl -9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride.  
 
     
     
         33 . A salt according to  claim 1 , which is: 
 4-(N-(2-Dimethylaminoethyl)-N-cyclopropyloxomethyl)amino -2-methyl-10-(2,4,6-trimethylphenyl)-5,6,7,8,9-pentahydrocyclohepta[1,2-d]pyridino[2,3-b]pyrrole sulfate;    4-(N-(2-Dimethylaminoethyl)-N-cyclopropylmethyl)amino -2-methyl-10-(2,4,6-trimethylphenyl) -5,6,7,8,9-pentahydrocyclohepta[1,2-d]pyridino[2,3-b]pyrrole sulfate;    4-(N-(2-Pyrrolidinoethyl)-N-propyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Dimethylaminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4-dimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Pyrrolidinoethyl)-N-(1-oxobutyl))amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N— (2-Pyrrolidinoethyl) —N— (2-methoxy-1-oxoethyl))amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Aminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4-dimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole citrate;    4-(N-(2-Pyrrolidinoethyl)-N-ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Dimethylaminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Pyrrolidinoethyl)-N-(2-methoxyethyl))amino -2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate; and    4-(N-(2-Pyrrolidinoethyl)-N-butyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate.    
     
     
         34 . A salt according to  claim 1 , which is: 
 4-(N-(2-Dimethylaminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,6-dimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Aminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride;    4-(N-(2-Pyrrolidinoethyl)-N-(1-oxopropyl))amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Pyrrolidinoethyl)-N-(1-oxoethyl))amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Aminoethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,6-dimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole sulfate;    4-(N-(2-Dimethylaminoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyrimidino[4,5-b]indole mesylate;    4-Piperazinyl-2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole tartrate;    4-(N-(2-(Ethylmethylamino)ethyl)-N-2-methylpropyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole mesylate;    4-(N-(2-Pyrrolidinoethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4-dimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride;    4-(N-(2-(2-Methylimidazolinyl)ethyl)-N-cyclopropylmethyl)amino -2-methyl-9-(2,4,6-trimethylphenyl) -5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole mesylate;    4-(N— (2-Pyrrolidinoethyl) —N— (1-oxopropyl))amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole mesylate; and    4-(N-(2-Pyrrolidinoethyl)-N-(1-oxoethyl))amino-2-methyl-9-(2,4,6-trimethylphenyl)-5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole dihydrochloride.    
     
     
         35 . A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of formula in any one of  claim 1 .  
     
     
         36 . The use of a compound for the manufacture of a medicament for the treatment of affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of formula in  claim 1 .  
     
     
         37 . A process for the preparation of a compound as claimed in  claim 1.