JP-2022514254-A5 -

Dates

Publication Date

20221226

Application Date

20191217

Description

While several aspects of several embodiments have been described, various modifications, refinements, and improvements will be readily apparent to those skilled in the art. Such modifications, refinements, and improvements are intended to be part of the disclosure and within the scope of the spirit of the disclosure. Accordingly, the foregoing description and drawings are merely illustrative. The invention described in the original claims of this application is listed below. [Claim 1] Equation (I) (Here R1 is selected from the group consisting of -OR a and 5-6 member heteroaryls; R2 and R3 are each independently selected from the group consisting of H, C1-6 alkyl, -ORb , -C0-6 alkylene - SO2R4 , and -C (O)OR5 ; R4 is -OR5 , C1-6 alkyl, C1-6 haloalkyl, heteroC1-6 alkyl , C1-6 hydroxyalkyl, C3-8 cycloalkyl, C0-6 alkyl ; R 5 is H or C 1-6 alkyl; Ra is selected from the group consisting of H, -P(O)(Rb ) 2 , -C(O) Rc , -C(O)ORc , C1-6 alkyl , and C1-6 hydroxyalkyl ; Each R b is independently selected from the group consisting of H and C1-6 alkyl groups; and Each Rc is independently selected from the group consisting of H, C1-6 alkyl , and C1-6 hydroxyalkyl. A compound of or a pharmaceutically acceptable salt thereof. [Claim 2] The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R1 is -OR a . [Claim 3] The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R1 is a 5-6 membered heteroaryl compound. [Claim 4] R1 is hydroxyl, A compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, selected from the group consisting of and five-membered heteroaryl compounds. [Claim 5] R2 and R3 are each independently selected from the group consisting of H and -ORb , the compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof. [Claim 6] R2 and R3 are each independently selected from the group consisting of H, C1-6 alkyl , and -C0-6 alkylene - SO2R4 , the compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof. [Claim 7] R2 and R3 are each independently selected from the group consisting of H, hydroxyl, -C0-6 alkylene - SO2R4 , and -C(O)OR5 , the compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof. [Claim 8] The compound described in claim 1 or a pharmaceutically acceptable salt thereof (Here R1 is hydroxy, Selected from the group consisting of; R2 and R3 are each independently selected from the group consisting of H, C1-6 alkyl, -ORb , -C0-6 alkylene - SO2R4 , and -C (O)OR5 ; R4 is -OR5 , C1-6 alkyl , C1-6 haloalkyl, heteroC1-6 alkyl, C1-6 hydroxyalkyl, and C3-8 cycloalkyl C0-6 alkyl ; and R5 is H or C1-6 alkyl ) . [Claim 9] Structural formula (I)-A or (I)-B: A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, having the above. [Claim 10] Structural formula (I)-C or (I)-D: A compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, having the above. [Claim 11] Structural formula (I)-E or (I)-F: A compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, having the above. [Claim 12] The compound is selected from the following: the compound according to claim 1 or a pharmaceutically acceptable salt thereof. [Claim 13] A pharmaceutical composition comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 12, and one or more pharmaceutically acceptable carriers. [Claim 14] A combination of pharmaceuticals comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 12, and one or more therapeutically active substances. [Claim 15] A method for treating a disorder or disease mediated by the mTOR pathway in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 13, or a combination of pharmaceuticals according to claim 14. [Claim 16] A method for treating a disease or disorder in a subject, wherein a target tissue, organ, or cell related to the pathophysiology of the disease or disorder has an FKBP12 level insufficient to inhibit mTORC1, and the method comprises administering a therapeutically effective amount of a compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 13, or a combination of pharmaceuticals according to claim 14, to the subject in need. [Claim 17] The method according to claim 16, wherein the compound of formula (I) or a pharmaceutically acceptable salt thereof has a higher binding affinity to FKBP12, FKBP25, FKBP51, and/or FKBP52