Compounds and therapies for the prevention of vascular and non-vascular pathologies

A therapeutic method for preventing or treating a condition or symptom associated with Parkinson's disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is hydrogen or phenyl optionally substituted by 1, 2, or 3 V;
• R9 is heteroaryl, heteroaryl(C1-C3)alkyl, (C1-C4)alkoxycarbonyl(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2, or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for preventing or treating a condition or symptom associated with Alzheimer's disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl,(C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is hydrogen or phenyl optionally substituted by 1, 2, or 3 V;
• R9 is heteroaryl, heteroaryl(C1-C3)alkyl, (C1-C4)alkoxycarbonyl C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2, or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for preventing or treating a condition or symptom associated with an autoimmune disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is hydrogen or phenyl optionally substituted by 1 2, or 3 V;
• R9 is heteroaryl, heteroaryl(C1-C3)alkyl, (C1-C4)alkoxycarbonyl(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2 or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for lowering serum cholesterol comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V,
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is hydrogen or phenyl optionally substituted by 1, 2, or 3 V;
• R9 is heteroaryl, heteroaryl(C1-C4)alkyl, (C1-C4)alkoxycarbonyl(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2, or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for enhancing or promoting wound healing, comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is hydrogen or phenyl optionally substituted by 1, 2, or 3 V;
• R9 is heteroaryl, heteroaryl(C1-C3)alkyl, (C1-C4)alkoxycarbonyl(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2, or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(C2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administer to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is hydrogen or phenyl option substituted by 1, 2, or 3 V;
• R9 is heteroaryl, heteroaryl(C1-C3)alkyl, (C1-C4)alkoxycarbonyl(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2, or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoroethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro to together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof;
• and provided that Z is not —CH2— when R6 is phenyl, substituted only at the 4-position with —O(CH2)1-3Rk;
• wherein Rk is pyrrolidino, piperidino, 4-morpholino, dimethylamino, diethylamino, or hexamethyleneimino.

A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is hydrogen or phenyl optionally substituted by 1, 2, or 3 V;
• R9 is heteroaryl, heteroaryl(C1-C3)alkyl, (C1-C4)alkoxycarbonyl(C1-C6)alkyl, (C314 C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2, or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C6)alkylthio, halo, trifluoromethyl, pentafluoroethyl nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof;
• and provided that Z is not —CH2— when R6 is phenyl, substituted only at the 4-position with —O(CH2)1-3 Rk;
• wherein Rk is pyrrolidino, piperidino, morpholino, dimethylamino, diethylamino, or hexamethyleneimino.

A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C6)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C1-C6)cycloalkenyl;
• R8 is hydrogen or phenyl optionally substituted by 1, 2, or 3 V;
• R9 is heteroaryl, heteroaryl(C1-C3)alkyl, (C1-C4)alkoxycarbonyl(C1-C6)alkyl(C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2, or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm) or S;
• Z is —O—, —OCH2—, —CH2O—, —C(═O)O—, or —N(Rq)—;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkoxy,(C1-C6)alkylcyclo(C1 -C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is hydrogen or phenyl optionally substituted by 1, 2, or 3 V;
• R9 is heteroalkyl, heteroaryl(C1-C3)alkyl, (C1-C4)alkoxycarbonyl(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl, wherein any aryl or heteroaryl may optionally be substituted by 1, 2, or 3, V;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Rn), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• the compound is MER25;
• or a pharmaceutically acceptable salt thereof;
• provided R6 is not phenyl or phenyl substituted by 1 or 2 V.

A therapeutic method for preventing or treating a condition or symptom associated with Marfan's syndrome, fibrosis, or senile dementia, comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —S—, —O—, —N(H)—, —N{(C1-C6)alkyl}—, —OCH2—, —OC{(C1-C6)alkyl}2—, or —CH═CH—;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, (CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(C2)1-3—, —O—, OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(Rl), S, or nonperoxide O, wherein Rl is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which the are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for preventing or treating a condition or symptom associated with Parkinson's disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —S—, —O—, —N(H)—, —N{(C1-C6)alkyl}—, —OCH2—, —OC{(C1-C6)alkyl}2—, or —CH═CH—;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V iS OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof;
• provided that R9 and Rj together are not —S— when Z is C═O;
• R6 is a phenyl radical substituted only at the 4-position with a group O(CH2)2Rk;
• Rk is pyrrolidino, piperidino, or hexamethyleneimino;
• R7 is phenyl substituted only at the 4-position with hydroxy, (C1-C2)alkoxy, —C(═O)(C1-C6)alkyl, or benzoyl;
• R8 is phenyl substituted only at the 4-position with hydroxy, (C1-C2)alkoxy, —C(═O)(C1-C6)alkyl, or benzoyl and at the 2-position with Rj;
• and — — — — — is a single bond.

A therapeutic method for preventing or treating a condition or symptom associated with Alzheimer's disease comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —S—, —O— —N(H)—, —N{(C1-C6)alkyl}—, —OCH2—, —OC{(C1-C6)alkyl}2—, or —CH═CH—;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro) cyano, trifluoroethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof;
• and provided that R9 and Rj together are not —CH2CH2—, —S—, —O— or —CH═CH— when Z is C═O;
• R6 is a phenyl radical substituted only at the 4-position with a group —O(CH2)1-4Rk, Rk is piperazino, heptamethyleneiminyl, imidazolinyl, pyrrolidino, piperidino, morpholinyl or hexamethyleneimino;
• R7 is phenyl substituted only at the 4-position with hydroxy, halo, (C1-C6)alkoxy, or —OC(═O)(C1-C6)alkyl;
• R8 is phenyl, substituted only at the 4-position with hydroxy, halo, (C1-C6)alkoxy, or —OC(═O)(C1-C6)alkyl and at the 2-position with Rj;
• and — — — — — is a single bond.

A therapeutic method for preventing or treating a condition or symptom associated with an autoimmune diseaSe comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —S—, —O— —N(H)—, —N{(C1-C6)alkyl}—, —OCH2—, —OC{(C1-C6)alkyl}2—, or —CH═CH—;
• — — — — — is a single bond or —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein R1 is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5 or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof;
• and provided that R9 and Rj together are not —S— when Z is C═O;
• R6 is a phenyl radical substituted only at the 4-position with a group —O(CH2)2Rk;
• Rk is pyrrolidino, piperidino, or hexamethyleneimino;
• R7 is phenyl substituted only at the 4-position with hydroxy, (C1-C2)alkoxy, —C(═O)(C1-C6)alkyl, or benzoyl;
• R8 is phenyl substituted only at the 4-position with hydroxy, (C1-C2)alkoxy, —C(═O)(C1-C6)alkyl, or benzoyl and at the 2-position with Rj;
• and — — — — — is a single bond.

A therapeutic method for lowering serum cholesterol comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —S—, —O— —N(H)—, —N{(C1-C6)alkyl}—, or —CH═CH—;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(Rl), S, or nonperoxide O, wherein Rl is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof;
• provided the compound of formula VI is not raloxifene.

A therapeutic method for enhancing or promoting wound healing, comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —S—, —O— —N(H)—, —N{(C1-C6)alkyl}—, —OCH2—, —OC{(C1-C6)alkyl}2—, or —CH═CH—;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(Rl), S, or nonperoxide O, wherein Rl is H(C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —S—, —O—, —N(H)—, —N{(C1-C6)alkyl}-, or —CH═C—;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C6)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(R1), S, or nonperoxide O, wherein Rl is H (C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof;
• and provided that Z is not —CH2— when R6 is phenyl, substituted only at the 4-position with —O(CH2)1-3Rk;
• wherein Rk is pyrrolidino, piperidino, 4-morpholino, dimethylamino, diethylamino, or hexamethyleneimino.

A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are R9 and Rj together are —CH2CH2—, —O—, —N(H)—, —N{(C1-C6)alkyl}-, or —CH═CH—,
• — — — — 13 is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORl, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(Rl), S, or nonperoxide O, wherein Rl is H(C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof;
• and provided that Z is not —CH2— when R6 is phenyl, substituted only at the 4-position with —O(CH2)1-3Rk;
• wherein Rk is pyrrolidino, piperidino, 4-morpholino, dimethylamino, diethylamino, or hexamethyleneimino.

A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl, or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —O—, —N(H)—, —N{(C1-C6)alkyl}-, —OCH2—, —OC{(C1-C6)alkyl}2—, or —CH═CH—;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl, or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH2)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —O—, —OCH2—, —CH2O—, —C(═O)O—, or —N(Rq)—;
• Rk is amino optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(Rl), S, or nonperoxide O, wherein Rl is H(C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rq are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof.

A therapeutic method for preventing or treating a condition or symptom associated with osteoporosis comprising administering to a mammal in need of such therapy, an effective amount of a compound of formula VI:

• wherein
• R6 is (C1-C6)alkyl, or aryl, optionally substituted by 1, 2, or 3 V;
• R7 is phenyl, optionally substituted by 1, 2, or 3 V;
• or R7 is (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkylcyclo(C1-C6)alkyl, (C3-C6)cycloalkenyl or (C1-C6)alkyl(C3-C6)cycloalkenyl;
• R8 is phenyl substituted at the 2-position with Rj, and optionally substituted by 1, 2, or 3 V;
• R9 and Rj together are —CH2CH2—, —S—, —O—, —N(H)—, —N{(C1-C6)alkyl}-, —OCH2—, —OC{(C1-C6)alkyl}2-, or —CH═CH—;
• — — — — — is a single bond or is —C(B)(D)—, wherein B and D are each independently hydrogen, (C1-C6)alkyl or halo;
• V is OPO3H2, (C1-C6)alkyl, (C1-C6)alkoxy, mercapto, (C1-C4)alkylthio, halo, trifluoromethyl, pentafluoroethyl, nitro, N(Rn)(Ro), cyano, trifluoromethoxy, pentafluoroethoxy, benzoyl, hydroxy, —(CH2)0-4C(═O)(C1-C6)alkyl, —UC(═O)(C1-C6)alkyl, benzyl, —OSO2(CH2)0-4CH3, —U(CH2)1-4COORp, —(CH2)0-4COORp, —U(CH2)2-4ORp, —(CH2)0-4ORp, —U(CH2)1-4C(═O)Rk, —(CH2)0-4C(═O)Rk, —U(CH2)1-4Rk, —(CH)0-4Rk, or —U(CH2)2-4OC(═O)Rp;
• wherein U is O, N(Rm), or S;
• Z is —(CH2)1-3—, —O—, —OCH2—, —CH2O—, —C(═O)O—, —N(Rq)—, C═O, or a covalent bond;
• Rk is amino, optionally substituted with one or two (C1-C6)alkyl;
• or an N-heterocyclic ring optionally containing 1 or 2 additional N(Rl), S, or nonperoxide O, wherein Rl is H(C1-C6)alkyl, phenyl, or benzyl;
• Rn and Ro are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or Rn and Ro together with the nitrogen to which they are attached are a 3, 4, 5, or 6 membered heterocyclic ring;
• Rp is H or (C1-C6)alkyl;
• and
• Rm and Rl are independently hydrogen, (C1-C6)alkyl, phenyl, benzyl, or (C1-C6)alkanoyl;
• or a pharmaceutically acceptable salt thereof;
• provided R6 is not phenyl or phenyl substituted by 1 or 2 V.