Heterocyclic compounds and methods for their use

摘要

The present invention relates to heterocyclic compounds useful for antagonizing angiotensin II Type 2 (AT2) receptor. More particularly the invention relates to piperidine compounds, compositions containing them and their use in methods of treating or preventing disorders or diseases associated with AT2 receptor function including neuropathic pain, inflammatory pain, conditions associated with neuronal hypersensitivity, impaired nerve conduction velocity, cell proliferation disorders, disorders associated with an imbalance between bone resorption and bone formation and disorders associated with aberrant nerve regeneration.

主权项

1. A compound of formula (I): wherein R1 is —C(═O)CH(aryl)(aryl), —C(═O)CH(aryl)(cycloalkyl), —C(═O)CH(cycloalkyl)(cycloalkyl), —C(═O)N(aryl)(aryl), —C(═O)N(aryl)(cycloalkyl) or —C(═O)N(cycloalkyl)(cycloalkyl); R2 is —CH2phenyl, —CH2CH2phenyl, —CH2CH2CH2phenyl, —OCH2phenyl, —OCH2CH2phenyl, —OCH2CH2CH2phenyl, —CH2CH═CHphenyl, —OCH2CH═CHphenyl, —OCH2C≡Cphenyl, —CH2C≡Cphenyl, —CH2OCH2phenyl, —CH2Ophenyl, —N(CH3)(2-phenypropyl), —N(CH3)(3-phenylpropyn-1-yl), —N(CH3)(phenethyl), -3-benzylmorpholine, —N(CH3)(benzyl), —N(CH3)(CH2C≡CCH3), —N(CH3)(CH2C≡CCH(CH3)2, —N(CH3) (CH2C≡C-4-fluorophenyl), —N(CH3)(CH2-4-phenyl-5-tetrazolyl), —N(CH3)(CH2-2-phenyl-1-cyclopent-1-enyl), —OCH2C≡C-4-fluorophenyl, —N(CH3)(CH2C≡CCF3), —N(CH3)(CH2C≡C—C(CH3)3, -3-phenylpiperidine, —N(CH3)(CH2C≡Cphenyl); 2-(5-phenyl)oxazolyl or 2-(5-benzyl)oxazolyl) R3b is hydrogen and R3a is —CO2H, —CH2CO2H, —C(═O)C(═O)OH, —C(═O)NH2, —CN, tetrazolyl —C(═O)NHSO2N(C1-6alkyl)2, —C(═O)NHSO2C1-6alkyl, —C(═O)NHSO2phenyl, —C(═O)NHSO2CF3—SO3H or —PO3H2; R4 is hydrogen; or a pharmaceutically acceptable salt thereof.