Derivatives of tryptamine and analogous compounds, and pharmaceutical formulations containing them

Abstract

This invention relates to the administration of novel substituted tryptamines and related derivatives for the treatment of several types of medical conditions, such as prostate conditions, impotence, cardiovascula disorders, central nervous system and psychiatric disorders (such as sleep disorders, epilepsy and other convulsive disorders, anxiety, neurodegenerative diseases), chronobiological-based disorders (such as jet lag, delayed sleep syndrome, shift-work-associated sleep disorder or seasonal affective disorder), endocrine indications, neoplastic conditions, conditions associated with senescence, ophthalmological diseases, cluster headaches and migraines, and weight gain disorders.

1 . A method for treating a mammal suffering from a medical condition susceptible to alleviation by treatment with a medicament which interacts with the melatoninergic system which comprises administering to the mammal an effective amount of a pharmaceutical formulation comprising at least one member of the group consisting of the compounds of formula I  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable acid addition salt thereof wherein  
       each of R 1 , R 2  and R 3  is independently selected from among hydrogen, halogen, C 1-4  alkyl, C 1-4  alkoxy, NR′R″, N(R′)C(:O)R°, nitro, aryl, aryl-C 1-4  alkyl, or aryl-C 1-4  alkoxy, R° is C 1-4  alkyl or aryl, and each of R′ and R″ is independently H or C 1-4  alkyl, or R′=R″=ClCH 2 CH 2 , or NR′R″ constitutes a saturated heterocyclic ring containing 3-8 ring members; m is 0-4; t is 0-3; and X is NH, N—C 1-4  alkyl, O or S; provided that X is not NH when simultaneously (R 1 ) m  is 5-methoxy, R 2  is H or I and t=0, and that X is not S when simultaneously R 2  is H and m=t=0.  
     
     
         2 . The method of  claim 1 , wherein the medical condition comprises a prostate condition, impotence, cardiovascular disorder, central nervous system or psychiatric disorder, chronobiological-based disorder, endocrine indication, neoplastic condition, immune system disorder, condition associated with senescence, ophthamological disease, cluster headache and migraine, Tardive dyskinesia, diabetes or a weight gain disorder.  
     
     
         3 . The method of  claim 2 , wherein said prostate condition comprises benign or cancerous prostate growth.  
     
     
         4 . The method of  claim 2 , wherein said cardiovascular disorder comprises hypertension, undesired blood coagulation, ischemic stroke or brain damage from stroke.  
     
     
         5 . The method of  claim 2 , wherein said central nervous system or psychiatric disorder comprises a sleep disorder, epilepsy or other convulsive disorder, anxiety, depression, mania, neuropathy, a neurodegenerative disease, MS, ALS, condition associated with dementia or cognitive impairment, fever or analgesia.  
     
     
         6 . The method of  claim 2 , wherein said chronobiological-based disorder comprises jet lag, a circadian sleep disorder or seasonal-related disorder.  
     
     
         7 . The method of  claim 6 , wherein said carcadian sleep disorder comprises delayed sleep syndrome or shift-work sleep disorder.  
     
     
         8 . The method of  claim 6 , wherein said seasonal-related disorder is seasonal affective disorder.  
     
     
         9 . The method of  claim 2 , wherein said endocrine indication comprises infertility, precocious puberty, premenstrual sysndrome, hyperprolactinemia, or growth hormone deficiency.  
     
     
         10 . The method of  claim 2 , wherein said compound is administered as a contraceptive agent.  
     
     
         11 . The method of  claim 2 , wherein said immune system disorder is AIDS.  
     
     
         12 . The method of  claim 2 , wherein said weight gain disorder comprises leptin or obesity.  
     
     
         13 . The method of  claim 2 , wherein said pharmaceutical formulation is characterized by at least one of the following features: 
 (i) it is adapted for oral, rectal, parenteral, transbuccal, intrapulmonary or transdermal administration;    (ii) it is in unit dosage form, each unit dosage comprising an amount of said at least one member which lies within the range of 0.0025-1000 mg;    (iii) it is a controlled release formulation, wherein said at least one member is released at a predetermined controlled rate.    
     
     
         14 . A method of treating a non-human mammal so as to regulate said mammal's fertility, puberty or pelage color which comprises administering to the mammal an effective amount of a pharmaceutical formulation comprising at least one member of the group consisting of the compounds of formula I or a pharmaceutically acceptable acid addition salt thereof,  
       wherein each of R 1 , R 2  and R 3  is independently selected from among hydrogen, halogen, C 1-4  alkyl, C 1-4  alkoxy, NR′R″, N(R′)C(:O)R°, nitro, aryl, aryl-C 1-4  alkyl, or aryl-C 1-4  alkoxy, R° is C 1-4  alkyl or aryl, and each of R′ and R″ is independently H or C 1-4  alkyl, or R′=R″=ClCH 2 CH 2 , or NR′R″ constitutes a saturated heterocyclic ring containing 3-8 ring members; m is 0-4; t is 0-3; and X is NH, N—C 1-4  alkyl, O or S; provided that X is not NH when simultaneously (R 1 ) m  is 5-methoxy, R 2  is H or I and t=0, and that X is not S when simultaneously R 2  is H and m=t=0.  
     
     
         15 . A method for preventing a medical condition in a mammal which is susceptible to alleviation by treatment with a medicament which interacts with the mammal's melatoninergic system which comprises administering to the mammal an effective amount of a pharmaceutical formulation comprising at least one member of the group consisting of the compounds of formula I or an acid addition salt thereof,  
       wherein each of R 1 , R 2  and R 3  is independently selected from among hydrogen, halogen, C 1-4  alkyl, C 1-4  alkoxy, NR′R″, N(R′)C(:O)R°, nitro, aryl, aryl-C 1-4  alkyl, or aryl-C 1-4  alkoxy, R° is C 1-4  alkyl or aryl, and each of R′ and R″ is independently H or C 1-4  alkyl, or R′=R″=ClCH 2 CH 2 , or NR′R″ constitutes a saturated heterocyclic ring containing 3-8 ring members; m is 0-4; t is 0-3; and X is NH, N—C 1-4  alkyl, O or S; provided that X is not NH when simultaneously (R 1 ) m  is 5-methoxy, R 2  is H or I and t=0, and that X is not S when simultaneously R 2  is H and m=t=0.  
     
     
         16 . The method of  claim 15 , wherein said condition comprises a prostate condition, impotence, cardiovascular disorder, central nervous system or psychiatric disorder, chronobiological-based disorder, endocrine indication, neoplastic condition, immune system disorder, condition associated with senescence, ophthamological disease, cluster headache and migraine, Tardive dyskinesia, diabetes or a weight gain disorder.