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US 6,887,868 B2Granted
Therapeutic 5-HT ligand compounds
AssigneePharmacia & Upjohn Company
InventorJian-Min Fu
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of Formula (I): wherein: R1, R2, R3, R4, R5, R6 R7, R8, n, m, and X have any of the values defined in the specification, as well as pharmaceutical compositions comprising the compounds. The invention also provides therapeutic methods as well as processes and intermediates useful for preparing compounds of Formula (I). The compounds are 5-HT ligands and are useful for treating diseases wherein modulation of 5-HT activity is desired.
Claims34
A compound of Formula I:
- wherein:
- R1 and R2 are independently hydrogen, C1-8alkyl, substituted C1-8alkyl, aryl(C1-8)alkylene, cycloalkyl, substituted cycloalkyl or heteroaryl (C1-8)alkylene;
- R3 and R4 are independently hydrogen, C1-8alkyl, aryl(C1-8)alkylene, or heteroaryl (C1-8)alkylene;
- R5 and each R6 are independently hydrogen, C1-8alkyl, aryl, heteroaryl, aryl(C1-8)alkylene or heteroaryl(C1-8)alkylene;
- each R7 is independently halo, cyano, nitro, trifluoromethyl, azido, C1-8alkyl, hydroxy, NRaRb, C1-8alkoxy, aryloxy, —C(═O)NRaRb, —C(═S)NRaRb, —C(═NRc)NRaRb, —NRcC(═NRc)NRaRb, —NRcC(═S)NRaRb, —NRcC(O)NRaRb, —NRcC(NCN)NRaRb, aryl or heteroaryl;
- X is O;
- n is 0, 1, 2, or 3;
- m is 1;
- Ra and Rb are each independently hydrogen, C1-8alkyl, aryl, aryl(C1-8)alkylene, heteroaryl, or heteroaryl(C1-8)alkylene;
- or Ra and Rb, together with the nitrogen to which they are attached, form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;
- each Rc is independently hydrogen, C1-8alkyl, aryl(C1-8)alkylene or heteroaryl(C1-8)alkylene;
- Rd and Re are each independently hydrogen, C1-8alkyl, aryl, aryl(C1-8)alkylene, heteroaryl, or heteroaryl(C1-8)alkylene;
- the bond represented by ——— is a single bond or a double bond;
- R8 is absent when the bond represented by ——— is a double bond;
- or when the bond represented by ——— is a single bond, R8 is hydrogen, halo, hydroxy, C1-8alkyl, C1-8alkoxy, aryl(C1-8)alkylene, heteroaryl(C1-8)alkylene, aryloxy(C1-8)alkylene or heteroaryloxy(C1-8)alkylene;
- wherein any aryl or heteroaryl of R1-R8 and Ra-Re is optionally substituted with one to four halo, cyano, nitro, trifluoromethyl, azido, C1-8alkyl, hydroxyl, NRfRg, C1-8alkoxy, aryloxy, —C(═O)NRfRg, —C(═S)NRf Rg, —C(═NRh)NRfRg, —NRhC(═NRh) NRfRg, —NRhC(═S) NRfRg, —NRhC(O)NRfRg, —NRhC(NCN)NRfRg, aryl or heteroaryl;
- wherein Rf and Rg are each independently hydrogen, C1-8alkyl, aryl, aryl(C1-8)alkylene, heteroaryl, or heteroaryl(C1-8)alkylene;
- or Rf and Rg, together with the nitrogen to which, they are attached, form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;
- each Rh is independently hydrogen, C1-8alkyl, aryl(C1-8)alkylene or heteroaryl(C1-8)alkylene;
- wherein any alkylene is optionally partially unsaturated;
- or a pharmaceutically acceptable salt thereof.
18 more elements
A compound according to Formula IV:
- wherein
- R3 and R4 are independently hydrogen, C1-8alkyl, aryl(C1-8)alkylene, or heteroaryl(C1-8)alkylene;
- R5 and each R6 are independently hydrogen, C1-8alkyl, aryl, heteroaryl, aryl(C1-8)alkylene or heteroaryl(C1-8)alkylene;
- each R7 is independently halo, cyano, nitro, trifluoromethyl, azido, C1-8alkyl, hydroxy, NRaRb, C1-8alkoxy, aryloxy, —C(═O)NRaRb, —C(═S)NRaRb, —C(═NRc)NRaRb, —NRcC(═NRc)NRaRb, —NRcC(═S)NRaRb, —NRcC(O)NRaRb, —NRcC(NCN)NRaRb, aryl or heteroaryl;
- X is O;
- n is 0, 1, 2, or 3;
- m is 1;
- Ra and Rb are each independently hydrogen, C1-8alkyl, aryl, aryl(C1-8)alkylene, heteroaryl, or heteroaryl(C1-8)alkylene;
- or Ra and Rb, together with the nitrogen to which they are attached, form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;
- each Rc is independently hydrogen, C1-8alkyl, aryl(C1-8)alkylene or heteroaryl(C1-8)alkylene;
- Rd and Re are each independently hydrogen, C1-8alkyl, aryl, aryl(C1-8)alkylene, heteroaryl, or heteroaryl(C1-8)alkylene;
- the bond represented by ——— is a single bond or a double bond;
- R8 is absent when the bond represented by ——— is a double bond;
- or when the bond represented by ——— is a single bond, R8 is hydrogen, halo, hydroxy, C1-8alkyl, C1-8alkoxy, aryl(C1-8)alkylene, heteroaryl(C1-8)alkylene, aryloxy(C1-8)alkylene or heteroaryloxy(C1-8)alkylene;
- wherein any aryl or heteroaryl of R1—R8 and Ra—Re is optionally substituted with one to four halo, cyano, nitro, trifluoromethyl, azido, C1-8alkyl, hydroxyl, NRfRg, C1-8alkoxy, aryloxy, —C(═O)NRfRg, —C(═S)NRf Rg, —C(═NRh)NRfRg, —NRhC(═NRh)NRfRg, —NRhC(═S)NRfRg, —NRhC(O)NRfRg, —NRhC(NCN)NRfRg, aryl or heteroaryl;
- wherein Rf and Rg are each independently hydrogen, C1-8alkyl, aryl, aryl(C1-8)alkylene, heteroaryl, or heteroaryl(C1-8)alkylene;
- or Rf and Rg, together with the nitrogen to which they are attached, form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;
- and
- each Rh is independently hydrogen, C1-8alkyl, aryl(C1-8)alkylene or heteroaryl(C1-8)alkylene;
- wherein any alkylene is optionally partially unsaturated.
17 more elements
Dependencies are inferred from the claim text.