Claims for Patent: 8,252,929

Summary for Patent: 8,252,929

Title:	8-carboxamido-2,6-methano-3-benzazocines
Abstract:	8-Substituted-2,6-methano-3-benzazocines of general structure I in which A is —CH2—OH, —CH2NH2, —NHSO2CH3, and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. 8-Carboxamides, thiocarboxamides, hydroxyamidines and formamides are preferred.
Inventor(s):	Mark P. Wentland
Assignee:	Rensselaer Polytechnic Institute
Application Number:	US13/103,599
Patent Claims:	1. A compound of formula: wherein A is Y is chosen from O and S; R1 is —NHR8; R2 and R2a are both hydrogen or taken together R2 and R2a are ═O; R3 is chosen from hydrogen, lower alkyl, alkenyl, aryl, heterocyclyl, benzyl and hydroxyalkyl; R4 is chosen from hydrogen, hydroxy, amino, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxy or carbonyl; R5 is lower alkyl; R6 is lower alkyl; R7 is chosen from hydrogen and hydroxy; or together R4, R5, R6 and R7 may form from one to three rings, said rings having optional additional substitution; and R8 is hydrogen. 2. A compound according to claim 1 wherein A is chosen from the group consisting of: —CONH2 and —C(═S)NH2. 3. A 2,6-methano-3-benzazocine according to claim 1 wherein: R4 is chosen from hydrogen, hydroxy, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxy or carbonyl; R5 is lower alkyl; R6 is lower alkyl; and R7 is hydrogen or hydroxy. 4. A 2,6-methano-3-benzazocine according to claim 3 wherein: R3 is chosen from hydrogen, cyclopropyl, cyclobutyl, phenyl, vinyl, dimethylvinyl, hydroxycyclopropyl, furanyl, and tetrahydrofuranyl; R4 is chosen from hydrogen and 3-oxo-5-cyclopentyl-1-pentanyl; R5 is methyl; and R6 is methyl or ethyl. 5. A morphinan according to claim 1 wherein together R5, R6 and R7 form two rings, said morphinan having the structure: wherein R4 is hydrogen, hydroxy, amino or lower alkoxy; R9 is hydrogen or lower alkyl; R10 is chosen from hydrogen, lower alkyl and hydroxy(lower alkyl); or together, R9 and R10 form a spiro-fused carbocycle of 5 to 10 carbons; R11 is hydrogen; R12 is chosen from hydroxy, lower alkoxy —NH2, —N(CH2CH2Cl)2, and —NHC(O)CH═CHCOOCH3; or together, R11 and R12 form a carbonyl or a vinyl substituent; or together, R4 and R11 form a sixth ring. 6. A morphinan according to claim 5, wherein R4 and R11 form a sixth ring, of formula 7. A morphinan according to claim 6 wherein R9 is hydrogen; R10 is hydroxy(lower alkyl); and R12 is lower alkoxy. 8. A morphinan according to claim 5, wherein R11 and R12 form a carbonyl substituent, of formula: 9. A morphinan according to claim 8 wherein R2 and R2a are both hydrogen; R4 is chosen from hydrogen, hydroxy, amino and lower alkoxy; and R9 and R10 are both hydrogen or together, R9 and R10 form a spiro-fused carbocycle of 5 to 10 carbons. 10. A morphinan according to claim 9 wherein R9 and R10 are both hydrogen. 11. A morphinan according to claim 5, wherein R11 and R12 form a vinyl substituent, of formula: 12. A morphinan according to claim 11 wherein R2 and R2a are both hydrogen; R4 is hydroxy; and R9 and R10 are both hydrogen. 13. A morphinan according to claim 5 wherein R2 and R2a are both hydrogen; R4 is hydroxy; R9 and R10 are both hydrogen; and R12 is chosen from: —NH2, —N(CH2CH2Cl)2, and —NHC(O)CH═CHCOOCH3. 14. A morphinan according to claim 1 wherein together R5, R6 and R7 form two rings, said morphinan having the structure: 15. A morphinan according to claim 5, wherein R4 and R11 form a sixth ring, of formula wherein R9 is hydrogen; R10 is hydroxy(lower alkyl); and R12 is lower alkoxy. 16. A 3-carboxamide substituted morphinan compound. 17. The morphinan compound of claim 16 having the formula: Wherein, R2 and R2a are both hydrogen; R3 is chosen from hydrogen, lower alkyl, alkenyl, aryl, heterocyclyl, benzyl and hydroxyalkyl; R4 hydroxyl; and, R9 and R10 are both hydrogen.