Antagonists of RF-amide neuropeptides
Disclosed are compounds having the formula: where R 1 =H, C 1 -C 6 alkyl, cycloalkyl, R 2 =H, C 1 -C 6 alkyl, cycloalkyl W=C n H 2n-m —NH (n=1-6, m=0, 2, or 4), X= R 3 = Y= Z=CONR 8 (CH 2 ) n , CONR 8 (CH 2 ) n CO, P(CH 3 )OCHR 8 OCOR 9 , SO 2 , SO 2 (CH 2 ) n , SO 2 (CH 2 ) n CO, SO 2 NR 8 (CH 2 ) n , SO 2 NR 8 (CH 2 ) n CO, n=1-4 R 4 =H, (CH 2 ) n OH, (CH 2 ) n OCOR 10 , (CH 2 ) n NR 10 R 11 , (CH 2 ) n CONR 10 R 11 , n=0-4 R 5 =H, (CH 2 ) n NR 12 R 13 , n=0-4 R 6 =H, (CH 2 ) n NR 14 R 15 , n=0-4 R 7 =H, C 1 -C 6 alkyl, cycloalkyl; R 8 =H, C 1 -C 6 alkyl, cycloalkyl; R 9 =H, C 1 -C 6 alkyl, cycloalkyl; R 10 =H, C 1 -C 6 alkyl, cycloalkyl; R 11 =H, C 1 -C 6 alkyl, cycloalkyl; R 12 =H, C 1 -C 6 alkyl, cycloalkyl; R 13 =H, C 1 -C 6 alkyl, cycloalkyl; R 14 =H, C 1 -C 6 alkyl, cycloalkyl; R 15 =H, C 1 -C 6 alkyl, cycloalkyl. Dashed lines: optional; conformational constraint by (CH 2 ) n , n=1-3, R′=H or O(═) as well as pharmaceuticals compositions and methods for the treatment of opiate addiction, opiate dependence, opiate tolerance, opiate related abstinence syndrome, nicotine addition and obesity based thereon.
1. An article of manufacture comprising packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent is effective for the treatment of a subject suffering from opiate addiction, and wherein said packaging material comprises a label which indicates that said pharmaceutical agent can be used for ameliorating the symptoms associated with opiate addiction, and wherein said pharmaceutical agent is selected from the group consisting of compounds having the formula:
where
R 1 =H, C 1 -C 6 alkyl, cycloalkyl,
R 2 =H, C 1 -C 6 alkyl, cycloalkyl
W=C n H 2n-m —NH (n=1-6, m=0, 2, or 4),
X=
R 3 =
Y=
Z=CONR 8 (CH 2 ) n , CONR 8 (CH 2 ) n CO, P(CH 3 )OCHR 8 OCOR 9 , SO 2 , SO 2 (CH 2 ) n , SO 2 (CH 2 ) n CO, SO 2 NR 8 (CH 2 ) n , SO 2 NR 8 (CH 2 ) n CO, n=1-4
R 4 =H, (CH 2 ) n OH, (CH 2 ) n OCOR 10 , (CH 2 ) n NR 10 R 11 , (CH 2 ) n CONR 10 R 11 , n=0-4
R 5 =H, (CH 2 ) n NR 12 R 13 , n=0-4
R 6 =H, (CH 2 ) n NR 14 R 15 , n=0-4
R 7 =H, C 1 -C 6 alkyl, cycloalkyl; R 8 =H, C 1 -C 6 alkyl, cycloalkyl; R 9 =H, C 1 -C 6 alkyl, cycloalkyl;
R 10 =H, C 1 -C 6 alkyl, cycloalkyl; R 11 =H, C 1 -C 6 alkyl, cycloalkyl; R 12 =H, C 1 -C 6 alkyl, cycloalkyl;
R 13 =H, C 1 -C 6 alkyl, cycloalkyl; R 14 =H, C 1 -C 6 alkyl, cycloalkyl; R 15 =H, C 1 -C 6 alkyl, cycloalkyl
Dashed lines: optional; conformational constraint by (CH 2 ) n , n=1-3; R′=H or O(═).
2. An article of manufacture comprising packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent is effective for the treatment of a subject suffering from opiate dependence, and wherein said packaging material comprises a label which indicates that said pharmaceutical agent can be used for ameliorating the symptoms associated with opiate dependence, and wherein said pharmaceutical agent is selected from the group consisting of compounds of claim 1 .
3. An article of manufacture comprising packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent is effective for the treatment of a subject suffering from opiate tolerance, and wherein said packaging material comprises a label which indicates that said pharmaceutical agent can be used for ameliorating the symptoms associated with opiate tolerance, and wherein said pharmaceutical agent is selected from the group consisting of compounds of claim 1 .
4. An article of manufacture comprising packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent is effective for the treatment of a subject suffering from opiate related abstinence syndrome, and wherein said packaging material comprises a label which indicates that said pharmaceutical agent can be used for ameliorating the symptoms associated with opiate related abstinence syndrome, and wherein said pharmaceutical agent is selected from the group consisting of compounds of claim 1 .
5. An article of manufacture comprising packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent is effective for the treatment of a subject suffering from nicotine addiction, and wherein said packaging material comprises a label which indicates that said pharmaceutical agent can be used for ameliorating the symptoms associated with nicotine addiction, and wherein said pharmaceutical agent is selected from the group consisting of compounds of claim 1 .
6. An article of manufacture comprising packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent is effective for the treatment of a subject suffering from obesity, and wherein said packaging material comprises a label which indicates that said pharmaceutical agent can be used for ameliorating the symptoms associated with obesity, and wherein said pharmaceutical agent is selected from the group consisting of compounds of claim 1 .