Bicyclic metabotropic glutamate receptor ligands

A compound of formula I:

• wherein
• R1, R2, R3, R4, R7, R8, R9, and R10 are each independently hydrogen, carboxy, tetrazolyl, —SO2OH, —PO(OH)2, —B(OH)2, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1-C6)alkoxycarbonyl, cyano, halo, —CONRaRb, —NRcRd, —SRe, aryl, heteroaryl, aryl(C1-C6)alkyl, diaryl(C1-C6)alkyl, or heteroaryl(C1-C6)alkyl, wherein any aryl or heteroaryl may optionally be substituted with 1, 2 or 3 substituents selected from the group consisting of halo, hydroxy, (C1-C6)alkoxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1-C6)alkoxycarbonyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, and carboxy;
• R5 is carboxy, tetrazolyl, (C1-C6)alkoxycarbonyl, —SO2OH, —B(OH)2, or —PO(OH)2;
• R6 is hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, aryl, aryl(C1-C6)alkyl, heteroaryl, heteroaryl(C1-C6)alkyl, (C1-C6)alkoxycarbonyl, or (C1-C6)alkanoyl;
• X is —C(Rf)(Rg)—;
• each Ra Rb and Re is independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heteroaryl, benzyl, or phenethyl;
• each Rc or Rd is independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, aryl, heteroaryl, benzyl, or phenethyl;
• or Rc and Rd together with the nitrogen to which they are attached are triazolyl, imidazolyl, oxazolidinyl, isoxazolidinyl, pyrrolyl, morpholino, piperidino, pyrrolidino, pyrazolyl, indolyl, or tetrazolyl;
• Rf and Rg are each independently hydrogen, carboxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1-C6)alkoxycarbonyl, cyano, halo, —CONRhRi, —NNjRk, —SRm, aryl, heteroaryl, aryl(C1-C6)alkyl, or heteroaryl(C1-C6)alkyl, wherein any aryl or heteroaryl may optionally be substituted with 1, 2 or 3 substituents selected from the group consisting of halo, hydroxy, (C1-C6)alkoxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1C6)alkoxycarbonyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, and carboxy;
• or Rf and Rg together are oxo (═O) or thioxo (═S);
• each Rh, Ri and Rm is independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heteroaryl, benzyl, or phenethyl;
• and
• each Rj or Rk is independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, aryl, heteroaryl, benzyl, or phenethyl;
• or Rj and Rk together with the nitrogen to which they are attached are triazolyl, imidazolyl, oxazolidinyl, isoxazolidinyl, pyrrolyl, morpholino, piperidino, pyrrolidino, pyrazolyl, indolyl, or tetrazolyl;or a pharmaceutically acceptable salt or prodrug thereof;
• wherein at least one of R1, R2, R3, R4, R9, and R10 is carboxy, tetrazolyl, —SO2OH, —PO(OH)2,or —B(OH)2.