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 --CH.sub.2--OH, --CH.sub.2NH.sub.2, --NHSO.sub.2CH.sub.3, ##STR00001## and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. ##STR00002## 8-Carboxamides, thiocarboxamides, hydroxyamidines and formamides are preferred.
Inventor(s):	Wentland; Mark P. (Watervliet, NY)
Assignee:	Rensselaer Polytechnic Institute (Troy, NY)
Application Number:	13/103,599
Patent Claims:	1. A compound of formula: ##STR00034## wherein A is ##STR00035## Y is chosen from O and S; R.sup.1 is --NHR.sup.8; R.sup.2 and R.sup.2a are both hydrogen or taken together R.sup.2 and R.sup.2a are .dbd.O; R.sup.3 is chosen from hydrogen, lower alkyl, alkenyl, aryl, heterocyclyl, benzyl and hydroxyalkyl; R.sup.4 is chosen from hydrogen, hydroxy, amino, lower alkoxy, C.sub.1-C.sub.20 alkyl and C.sub.1-C.sub.20 alkyl substituted with hydroxy or carbonyl; R.sup.5 is lower alkyl; R.sup.6 is lower alkyl; R.sup.7 is chosen from hydrogen and hydroxy; or together R.sup.4, R.sup.5, R.sup.6 and R.sup.7 may form from one to three rings, said rings having optional additional substitution; and R.sup.8 is hydrogen. 2. A compound according to claim 1 wherein A is chosen from the group consisting of: --CONH.sub.2 and --C(.dbd.S)NH.sub.2. 3. A 2,6-methano-3-benzazocine according to claim 1 wherein: R.sup.4 is chosen from hydrogen, hydroxy, lower alkoxy, C.sub.1-C.sub.20 alkyl and C.sub.1-C.sub.20 alkyl substituted with hydroxy or carbonyl; R.sup.5 is lower alkyl; R.sup.6 is lower alkyl; and R.sup.7 is hydrogen or hydroxy. 4. A 2,6-methano-3-benzazocine according to claim 3 wherein: R.sup.3 is chosen from hydrogen, cyclopropyl, cyclobutyl, phenyl, vinyl, dimethylvinyl, hydroxycyclopropyl, furanyl, and tetrahydrofuranyl; R.sup.4 is chosen from hydrogen and 3-oxo-5-cyclopentyl-1-pentanyl; R.sup.5 is methyl; and R.sup.6 is methyl or ethyl. 5. A morphinan according to claim 1 wherein together R.sup.5, R.sup.6 and R.sup.7 form two rings, said morphinan having the structure: ##STR00036## wherein R.sup.4 is hydrogen, hydroxy, amino or lower alkoxy; R.sup.9 is hydrogen or lower alkyl; R.sup.10 is chosen from hydrogen, lower alkyl and hydroxy(lower alkyl); or together, R.sup.9 and R.sup.10 form a spiro-fused carbocycle of 5 to 10 carbons; R.sup.11 is hydrogen; R.sup.12 is chosen from hydroxy, lower alkoxy --NH.sub.2, --N(CH.sub.2CH.sub.2Cl).sub.2, and --NHC(O)CH.dbd.CHCOOCH.sub.3; or together, R.sup.11 and R.sup.12 form a carbonyl or a vinyl substituent; or together, R.sup.4 and R.sup.11 form a sixth ring. 6. A morphinan according to claim 5, wherein R.sup.4 and R.sup.11 form a sixth ring, of formula ##STR00037## 7. A morphinan according to claim 6 wherein R.sup.9 is hydrogen; R.sup.10 is hydroxy(lower alkyl); and R.sup.12 is lower alkoxy. 8. A morphinan according to claim 5, wherein R.sup.11 and R.sup.12 form a carbonyl substituent, of formula: ##STR00038## 9. A morphinan according to claim 8 wherein R.sup.2 and R.sup.2a are both hydrogen; R.sup.4 is chosen from hydrogen, hydroxy, amino and lower alkoxy; and R.sup.9 and R.sup.10 are both hydrogen or together, R.sup.9 and R.sup.10 form a spiro-fused carbocycle of 5 to 10 carbons. 10. A morphinan according to claim 9 wherein R.sup.9 and R.sup.10 are both hydrogen. 11. A morphinan according to claim 5, wherein R.sup.11 and R.sup.12 form a vinyl substituent, of formula: ##STR00039## 12. A morphinan according to claim 11 wherein R.sup.2 and R.sup.2a are both hydrogen; R.sup.4 is hydroxy; and R.sup.9 and R.sup.10 are both hydrogen. 13. A morphinan according to claim 5 wherein R.sup.2 and R.sup.2a are both hydrogen; R.sup.4 is hydroxy; R.sup.9 and R.sup.10 are both hydrogen; and R.sup.12 is chosen from: --NH.sub.2, --N(CH.sub.2CH.sub.2Cl).sub.2, and --NHC(O)CH.dbd.CHCOOCH.sub.3. 14. A morphinan according to claim 1 wherein together R.sup.5, R.sup.6 and R.sup.7 form two rings, said morphinan having the structure: ##STR00040## 15. A morphinan according to claim 5, wherein R.sup.4 and R.sup.11 form a sixth ring, of formula ##STR00041## wherein R.sup.9 is hydrogen; R.sup.10 is hydroxy(lower alkyl); and R.sup.12 is lower alkoxy. 16. A 3-carboxamide substituted morphinan compound. 17. The morphinan compound of claim 16 having the formula: ##STR00042## Wherein, R.sup.2 and R.sup.2a are both hydrogen; R.sup.3 is chosen from hydrogen, lower alkyl, alkenyl, aryl, heterocyclyl, benzyl and hydroxyalkyl; R.sup.4 hydroxyl; and, R.sup.9 and R.sup.10 are both hydrogen.