Somatostatin antagonists and agonists that act at the SST subtype 2 receptor

A compound according to the formula

• A—Z—W (formula I)
• or a pharmaceutically acceptable salt, solvate, or hydrate thereof;
• wherein
• A is selected from the groups consisting of:
• A′—(CH2)n—, A′—(CH2)nSO2—, and A′—(CH2)nCO—, where n is 0 to 4;
• and
• A′ is selected from
• (a) (C6-C10)aryl-, selected from phenyl or naphthyl;
• or
• (b) (C1-C9)heteroaryl-, selected from the group consisting of furyl-, thienyl- thiazolyl-, pyrazolyl-, isothiazolyl-, oxazolyl-, isoxazolyl-, pyrrolyl-, triazolyl-, tetrazolyl-, imidazolyl-, 1,3,5-oxadiazolyl-, 1,2,4-oxadiazolyl-, 1,2,3-oxadiazolyl-, 1,3,5-thiadiazolyl-, 1,2,3-thiadiazolyl-, 1,2,4-thiadiazolyl-, pyridyl- pyrimidyl-, pyrazinyl-, pyridazinyl-, 1,2,4-triazinyl-, 1,2,3-triazinyl, 1,3,5-triazinyl-, pyrazolo[3,4-b]pyridinyl-, cinnolinyl-, pteridinyl-, purinyl-, 6,7-dihydro-5H-[1]pyrindinyl-, benzo[b]thiophenyl-, 5, 6, 7, 8-tetrahydro-quinolin-3-yl, benzoxazolyl, benzothiazolyl, benzisothiazolyl-, benzisoxazolyl-, benzimidazolyl-, thianaphthenyl-, isothianaphthenyl-, benzofuranyl-, isobenzofuranyl-, isoindolyl-, indolyl-, indolizinyl-, indazolyl-, isoquinolyl- quinolyl-, phthalazinyl-, quinoxalinyl-, quinazolinyl-, and benzoxazinyl-;
• wherein said A′ group (a) or (b) is optionally substituted by zero to seven groups, each independently selected from:
• hydroxy, halo, amino, trifluoromethyl-, carboxy, (C1-C6)alkoxy-, (C1-C6)acyloxy-, (C1-C6)alkylamino-, ((C1-C6)alkyl)2amino-, (C1-C6)acylamino-, cyano, nitro, (C1-C6)alkyl-, (C2-C6)alkenyl-, (C2-C6)alkynyl-, (C1-C6)acylamino-, cyano(C1-C6)alkyl-, trifluoromethyl(C1-C6)alkyl-, nitro(C1-C6)alkyl-, (C1-C3)alkyl(difluoromethylene)(C1-C3)alkyl-, (C1-C6)acylamino(C1-C6)alkyl-, (C1-C6)alkoxy(C1-C6)acylamino-, amino(C1-C6)acyl-, amino(C1-C6)acyl(C1-C6) alkyl-, (C1-C6)alkylamino(C1-C6)acyl-, ((C1-C6)alkyl)2amino(C1-C6)acyl-, (C3-C10)cycloalkyl(C1-C6)alkyl-, (C1-C6)acyloxy(C1-C6)alkyl-, (C2-C6)alkoxy(C1-C6)alkyl-, piperazinyl(C1-C6)alkyl-, (C1-C6)acylamino(C1-C6)alkyl-, (C6-C10)aryl(C1-C6)alkoxy(C1-C6)alkyl-, (C1-C9)heteroaryl(C1-C6)alkoxy(C1-C6)alkyl-, (C1-C6)alkylthio(C1-C6)alkyl-, (C6-C10 )arylthio(C1-C6)alkyl-, (C1-C6)alkylsulfinyl(C1-C6)alkyl-, (C6-C10)arylsulfinyl(C1-C6)alkyl-, (C1-C6)alkylsulfonyl(C1-C6)alkyl-, (C6-C10)arylsulfonyl(C1-C6)alkyl-, amino(C1-C6)alkyl-, (C1-C6)alkylamino(C1-C6)alkyl-, (C1-C6)alkyl(difluoromethylene)-, (C1-C3)alkyl(difluoromethylene)(C1-C3)alkyl-, (C1-C6)alkoxy(C1-C6)acyl-, (C1-C6)alkylamino(C1-C6)acyl-, ((C1-C6)alkyl)2amino(C1-C6)acyl-, (C6-C10)aryl-, (C1-C9)heteroaryl-, (C6-C10)aryl(C1-C6)alkyl-, (C1-C9)heteroaryl(C1-C6)alkyl-, (C6-C10)aryl(C6-C10)aryl-, (C6-C10)aryl(C6-C10)aryl(C1-C6)alkyl-, (C3-C10)cycloalkyl-, (C3-C6)cycloalkyl(C1-C6)alkyl-, (C3-C10)heterocycloalkyl-, (C3-C10)heterocycloalkyl(C1-C6)alkyl-, hydroxy(C2-C6)alkyl-, (C1-C6)acyloxy(C2-C6)alkyl-, (C1-C6)alkoxy(C2-C6)alkyl-, piperazinyl(C1-C6)alkyl-, (C1-C6)acylamino(C1-C6)alkyl-, (C6-C10)aryl(C1-C6)alkoxy(C1-C6)alkyl-, (C1-C9)heteroaryl(C1-C6)alkoxy(C1-C6)alkyl-, (C1-C6)alkylthio(C1-C6)alkyl-, (C6-C10)arylthio(C1-C6)alkyl-, (C1-C6)alkylsulfinyl(C1-C6)alkyl-, (C6-C10)arylsulfinyl(C1-C6)alkyl-, (C1-C6)alkylsulfonyl(C1-C6)alkyl-, (C6-C10)arylsulfonyl(C1-C6)alkyl-, amino(C1-C6)alkyl-, (C1-C6)alkylamino(C1-C6alkyl-, ((C1-C6)alkyl)2amino(C1-C6)alkyl-;
• Z is selected from group (i)
• where R13 is H, or (C1-C6)alkyl optionally substituted by one or more halo groups;
• R14 is H, (C1-C6)alkyl, trifluoro(C1-C6)alkyl-, or phenyl(CH2)—, wherein said alkyl and phenyl groups are each optionally substituted by one or more halo groups, or R14 is selected from the groups A above, optionally substituted by one or more halo groups;
• R15 is selected from hydrogen, hydroxy, halo, (C1-C6)alkyl- optionally substituted by one or more halo, and (C1-C6)alkoxy- optionally substituted by one or more halo;
• and
• J is S, O, —NH—, or NCH3;
• W is (a):
• wherein n is 2-5,
• R3 and R6 are independently selected from H, (C1-C8)alkyl-, phenyl (CH2)-, wherein said alkyl and phenyl groups are optionally substituted by one or more halo groups;
• R4 is selected from H, (C1-C8)alkyl-, and phenyl(CH2)-, wherein said alkyl and phenyl groups are optionally substituted by one or more halo groups;or is
• where groups R10, R11 and R11, are each, independently, selected from H, (C1-C8)alkyl-, and phenyl(CH2)—, wherein said alkyl and phenyl groups are optionally substituted by one or more halo groups;
• R5 is H, (C1-C8)alkyl-, and phenyl(CH2)-, wherein said alkyl and phenyl groups are optionally substituted by one or more halo groups;
• or is
• wherein R12 and R12′ are each independently selected from H, (C1-C8)alkyl-, and phenyl(CH2)—, wherein said alkyl and phenyl groups are optionally substituted by one or more halo groups;
• or W is (b)
• wherein Q is selected from the group consisting of:
• (i) (C6-C10)aryl-, selected from phenyl or naphthyl;
• (ii) (C1-C9)heteroaryl-, selected from the group consisting of furyl-, thienyl- thiazolyl-, pyrazolyl-, isothiazolyl-, oxazolyl-, isoxazolyl-, pyrrolyl-, triazolyl-, tetrazolyl-, imidazolyl-, 1,3,5-oxadiazolyl-, 1,2,4-oxadiazolyl-, 1,2,3-oxadiazolyl-, 1,3,5-thiadiazolyl-, 1,2,3-thiadiazolyl-, 1,2,4-thiadiazolyl-, pyridyl-, pyrimidyl-, pyrazinyl-, pyridazinyl-, 1,2,4- triazinyl-, 1,2,3-triazinyl-, 1,3,5-triazinyl-, pyrazolo[3,4-b]pyridinyl-, cinnolinyl-, pteridinyl-, purinyl-, 6,7-dihydro-5H-[1]pyrindinyl-, benzo[b]thiophenyl-, 5, 6, 7, 8-tetrahydro-quinolin-3-yl, benzoxazolyl-, benzothiazolyl-, benzisothiazolyl-, benzisoxazolyl-, benzimidazolyl-, thianaphthenyl-, isothianaphthenyl-, benzofuranyl-, isobenzofuranyl-, isoindolyl-, indolyl-, indolizinyl-, indazolyl-, isoquinolyl- quinolyl-, phthalazinyl-, quinoxalinyl-, quinazolinyl-, and benzoxazinyl-;
• (iii) (C3-C10)cycloalkyl that is selected from the group consisting of cyclopropyl-, cyclobutyl-, cyclopentyl-;
• cyclohexyl-, cycloheptyl-, cyclopropenyl-, cyclobutenyl- cyclopentenyl-, cyclohexenyl-, cycloheptenyl-, 1,3-cyclobutadienyl-, 1,3-cyclopentadienyl-, 1,3-cyclohexadienyl-, 1,4-cyclohexadienyl-1,3-cycloheptadienyl-, 1,4-cycloheptadienyl-, 1,3,5-cycloheptatrienyl- bicyclo[3.2.1]octane, bicyclo [2.2.1] heptane and the norborn-2-ene unsaturated form thereof;
• and
• (iv) (C3-C10)heterocycloalkyl that is selected from the group consisting of pyrrolidinyl-, tetrahydrofuranyl- dihydrofuranyl-, tetrahydropyranyl-, pyranyl-, thiopyranyl-, aziridinyl-, oxiranyl-, methylenedioxyl-, chromenyl-, isoxazolidinyl-, 1,3-oxazolidin-3-yl- isothiazolidinyl-, 1,3-thiazolidin-3-yl-, 1,2-pyrazolidin-2-yl-, 1,3-pyrazolidin-1-yl-, piperidinyl-, thiomorpholinyl-, 1,2-tetrahydrothiazin-2-yl-, 1,3-tetrahydrothiazin-3-yl-, tetrahydrothiadiazinyl-, morpholinyl-, 1,2-tetrahydrodiazin-2-yl-, 1,3-tetrahydrodiazin-1-yl-, tetrahydroazepinyl-, piperazinyl-, and chromanyl;
• and R7, R8, and R9 are each independently selected from H, (C1-C8)alkyl-, and phenyl(CH2)—, wherein said alkyl and phenyl groups are optionally substituted by one or more halo groups.