Claims for Patent: 5,827,871

Summary for Patent: 5,827,871

Title:	Medicaments 1,2,3,4-tetrahydrocarbazoles and 5-HT1 agonist use thereof
Abstract:	Use of a compound of general formula (I): Formula (I) wherein R1 represents hydrogen, halogen, trifluoromethyl, nitro, hydroxy, C1-6alkyl, C1-6alkoxy, arylC1-6alkoxy, -CO2R4, -(CH2)nCN, -(CH2)nCONR5R6, -(CH2)nSO2NR5R6, C1-6alkanoylamino(CH2)n, or C1-6alkylsulphonylamino(CH2)n; R4 represents hydrogen, C1-6alkyl or arylC1-6alkyl; R5 and R6 each independently represent hydrogen or C1-6alkyl, or R5 and R6 together with the nitrogen atom to which they are attached form a ring; n represents 0, 1 or 2; and R2 and R3 each independently represent hydrogen, C1-6alkyl or benzyl or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or hexahydroazepino ring; or a physiologically acceptable salt thereof, in the manufacture of a medicament for the treatment of a condition where a 5-HT1-like agonist is indicated, for example migraine. Novel compounds of formula (I), processes for preparing them and pharmaceutical compositions containing them are also described.
Inventor(s):	Francis David King, Laramie Mary Gaster, Alberto Julio Kaumann, Rodney Christopher Young
Assignee:	Endo Pharmaceuticals Inc
Application Number:	US08/442,720
Patent Claims:	1. A method of treatment of a condition wherein a 5-HT1 -like agonist is indicated, which comprises administering to a subject in need thereof an effective amount of a compound of general formula (I): ##STR9## wherein R1 represents hydrogen, halogen, trifluoromethyl, nitro, hydroxy, C1-6 alkyl, C1-6 alkoxy, arylC1-6 alkoxy, --CO2 R4, --(CH2)n CN, --(CH2)n CONR5 R6, --(CH2)n SO2 NR5 R6, C1-6 alkanoylamino(CH2)n, or C1-6 alkylsulphonylamino(CH2)n ;R4 represents hydrogen, C1-6 alkyl or arylC1-6 alkyl; R5 and R6 each independently represent hydrogen or C1-6 alkyl, or R5 and R6 together with the nitrogen atom to which they are attached form a 5 to 7-membered saturated heterocyclic ring, which may optionally contain a further heteroatom selected from oxygen, sulphur or nitrogen; n represents 0, 1 or 2; and R2 and R3 each independently represent hydrogen, C1-6 alkyl or benzyl or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or hexahydroazepino ring; or a physiologically acceptable salt, solvate or hydrate thereof. 2. The method according to claim 1 wherein the condition is migraine. 3. The method according to claim 1 wherein in the compound of formula (I) R1 represents halogen, CF3, C1-6 alkoxy, --(CH2)n CN, --(CH2)n CONR5 R6, --(CH2)n SO2 RN5 R6 or C1-6 alkanoylamino, and R5 and R6 are as hereinbefore defined. 4. The method according to claim 1 wherein in the compound of formula (I) R1 is a group --(CH2)n CONR5 R6 wherein n is zero and R5 and R6 each independently represent hydrogen, methyl, ethyl or propyl; and R2 and R3 each independently represent hydrogen, methyl or ethyl. 5. The method according to claim 2 wherein in the compound of formula (I) R1 is a group --(CH2)n CONR5 R6 wherein n is zero and R5 and R6 each independently represent hydrogen, methyl, ethyl or propyl; and R2 and R3 each independently represent hydrogen, methyl or ethyl. 6. The method according to claim 4 wherein in the compound of formula (I) R5 and R6 each independently represent hydrogen or methyl. 7. The method according to claim 5 wherein in the compound of formula (I) R5 and R6 each independently represent hydrogen or methyl. 8. A compound of formula (IA): ##STR10## wherein R1 represents nitro, --CO2 R4, CN, --(CH2)n CONR5 R6, --(CH2)n SO2 NR5 R6, or C1-6 alkylsulphonylamino(CH2)n ;R4 represents arylC1-6 alkyl; R5 and R6 each independently represent hydrogen or C1-6 alkyl, or R5 and R6 together with the nitrogen atom to which they are attached form a 5 to 7-membered saturated heterocyclic ring, which may optionally contain a further heteroatom selected from oxygen, sulphur or nitrogen; and n represents 0, 1 or 2; or a physiologically acceptable salt, solvate or hydrate thereof. 9. A compound of formula (IA) according to claim 8 wherein R1 represents --(CH2)n CONR5 R6, wherein n represents 0 and R5 and R6 each independently represent hydrogen, methyl, ethyl or propyl. 10. A compound of formula (IA) according to claim 9 wherein R5 and R6 each independently represent hydrogen or methyl. 11. A compound of formula (I) according to claim 8, which is selected from:3-Amino-6-cyano-1,2,3,4-tetrahydrocarbazole; 3-amino-6-(N-methylsulphonamidomethyl)-1,2,3,4-tetrahydrocarbazole; 3-amino-6-sulphonamido-1,2,3,4-tetrahydrocarbazole; 3-amino-6-nitro-1,2,3,4-tetrahydrocarbazole; 3-amino-6-(piperidin-1-ylcarbonyl)-1,2,3,4-tetrahydrocarbazole; 3-amino-6-(pyrrolidin-1-ylcarbonyl)-1,2,3,4-tetrahydrocarbazole; 3-amino-6-methanesulphonamido-1,2,3,4-tetrahydrocarbazole;or a physiologically acceptable salt, solvate or hydrate thereof. 12. A compound of formula (I) according to claim 8, which is selected from:3-amino-6-(N-methylcarboxamido)-1,2,3,4-tetrahydrocarbazole; 3-amino-6-(N,N-dimethylcarboxamido)-1,2,3,4-tetrahydrocarbazole; 3-amino-6-(N,N-diethylcarboxamido)-1,2,3,4-tetrahydrocarbazole;or a physiologically acceptable salt, solvate or hydrate thereof. 13. A compound of formula (I) according to claim 8, which is selected from:3-amino-6-carboxamidomethyl-1,2,3,4-tetrahydrocarbazole; 3-amino-6-(2-carboxamidoethyl)-1,2,3,4-tetrahydrocarbazole;or a physiologically acceptable salt, solvate or hydrate thereof. 14. A compound of formula (I) according to claim 8, which is (+)-3-amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole or a physiologically acceptable salt, solvate or hydrate thereof. 15. A compound of formula (I) according to claim 8, which is (-)-3-amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole or a physiologically acceptable salt, solvate or hydrate thereof. 16. A compound of formula (I) according to claim 8 wherein the said physiologically acceptable salt is formed from hydrochloric, sulphuric, phosphoric, succinic, maleic, acetic or fumaric acid. 17. A pharmaceutical composition comprising a compound of formula (I) according to claim 8, or a physiologically acceptable salt, solvate or hydrate thereof and a physiologically acceptable carrier.