PARATHYROID HORMONE 1 AND INCRETIN RECEPTOR AGONISTS COMPRISING SUBSTITUTED OR MODIFIED DIAMINOMETHYLENE-PYRIMIDINI-2,4,6-TRIONES

Claims

Compounds that are parathyroid hormone receptor 1 agonists and methods useful for preventing or treating osteoporosis, fractures, osteomalacia, arthritis, thrombocytopenia, hypoparathyroidism, hyperphosphatemia, or tumor calcinosis are described. GLP-1R, GCGR, and / or GIPR agonists and methods for treating various therapeutic indications by administering an effective amount of a GLP-1R, GCGR, and / or GIPR agonist are also described.

1. A compound characterized in that it conforms to formula (1) or a pharmaceutically acceptable salt thereof; wherein: R1 is (C1-C6)alkyl; R2 is hydrogen or (C1-C6)alkyl optionally substituted with hydroxy or heterocylcylalkyl of between 4 and 7 members; R3 is (C1-C6)alkyl optionally substituted with (C3-C8)cycloalkyl or phenyl; R4a and R4b are independently hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more instances of fluoro, hydroxy, or heterocycloalkyl of between 4 and 7 members; or R4a and R4b taken together with the nitrogen atom to which they are attached form a heterocycloalkyl of between 4 and 7 members; and R 5a and R 5b are independently hydrogen or (C1-C6)alkyl, wherein (C1-C6)alkyl is optionally substituted with one or more fluoro, hydroxy, or heterocycloalkyl instances of between 4 and 7 members;or R 5a and R 5b taken together with the nitrogen atom to which they are attached form a heterocycloalkyl of between 4 and 7 members; wherein at least one of R 4a and R 4b , R 5a and R 5b is hydrogen, and at least one of R 4a and R 4b , R 5a and R 5b is not hydrogen; provided that the compound is not: of formula (2). ; 72. A pharmaceutical composition characterized in that it comprises a compound of any one of claims 1 to 71, or a pharmaceutically acceptable salt thereof; and at least one pharmaceutically acceptable excipient.