Mixed
This invention features opioid compounds having activity at kappa and mu receptors, methods for preparing the mu/kappa opioids, and methods for the treatment of pain or a dopamine dysregulation disease, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), attention deficit hyperactivity disorder (ADD), Parkinson's disease, hyperprolactinemia, depression, and addiction.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein
X includes the carbon atoms at positions 1 and 2 and is selected from
Y is H, oxo, or methyl;
R is selected from H, C 1-7 alkyl, C 2-7 alkenyl, C 2-7 alkynyl, C 2-6 heterocyclyl, C 6-12 aryl, C 7-14 alkaryl, C 3-10 alkheterocyclyl, and C 1-7 heteroalkyl;
R 1 is H;
R 4 is H and R 2 and R 3 combine to form a fused six-membered ring in which position 4 is connected to position 5 by
Z is —NHR 5 ; and
R 5 is H.
2. The compound of claim 1 , wherein said compound is described by formulas II or III:
or a pharmaceutically acceptable salt thereof, wherein R is selected from H, C 1-7 alkyl, C 2-7 alkenyl, C 2-7 alkynyl, C 2-6 heterocyclyl, C 6-12 aryl, C 7-14 alkaryl, C 3-10 alkheterocyclyl, and C 1-7 heteroalkyl.
3. The compound of claim 1 , wherein said compound is described by formula IX:
or a pharmaceutically acceptable salt thereof, wherein R is selected from H, C 1-7 alkyl, C 2-7 alkenyl, C 22-7 alkynyl, C 2-6 heterocyclyl, C 6-12 aryl, C 7-14 alkaryl, C 3-10 alkheterocyclyl, and C 1-7 heteroalkyl.
4. The compound of claim 2 or 3 , wherein R is selected from CH 3 , CH 2 (cyclo-C 4 H 7 ), CH 2 (cyclo-C 3 H 5 ), CH(CH 3 )(cyclo-C 3 H 5 ), CH 2 CH 2 CH 2 F, CH 2 CH 2 OCH 3 , CH 2 CH 2 OCF 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH═CH 2 , trans-CH 2 CH═CHI, CH 2 C≡CH, benzyl, phenethyl, 3,4-dichlorophenethyl, 3-furanylmethyl, 2-furanylmethyl, 3-tetrahydrofuranylmethyl, and 2-tetrahydrofuranylmethyl.
5. The compound of claim 4 , wherein said compound has the structure
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising an effective amount of a compound of any of claims 1 , 2 , 3 , or 5 , or a suitable salt thereof together with a pharmaceutically acceptable carrier or diluent.
7. A method of treating pain in a patient in need thereof, said method comprising the step of administering to said patient a pharmaceutical composition of claim 6 in an amount sufficient to treat said pain.