Inhibitors of cyclic adp ribose hydrolase and methods of use thereof
AssigneeFlagship Pioneering Innovations VI, LLC
InventorsBenito Munoz, Hairuo Peng
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Abstract
The disclosure provides compounds, in part, compounds of Formula I or Formula II and their use in treating medical diseases or disorders, such as neurodegenerative diseases, e.g., Parkinson's disease. Pharmaceutical compositions and methods of making compounds of the disclosure are provided. The compounds are contemplated to be modulators, e.g., inhibitors, of cyclic ADP ribose hydrolase (CD38).
Claims33
A compound represented by Formula I:
- or a pharmaceutically acceptable salt and/or a stereoisomer thereof, wherein:
- R1 is 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl;
- wherein R1 may optionally be substituted by one or more substituents each independently selected from R11;
- R2 is selected from the group consisting of —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, and —C3-6cycloalkyl;
- wherein R2 may optionally be substituted by one or more substituents each independently selected from R22,
- R3 is selected from the group consisting of 5-6 membered monocyclic heteroaryl, 8-10 membered bicyclic heteroaryl, 4-10 membered heterocyclyl, and phenyl;
- wherein R3 may optionally be substituted by one or more substituents each independently selected from R33;
- R4 is selected from the group consisting of hydrogen and —C1-3alkyl optionally substituted by one or more halogens;
- R5 is selected from the group consisting of hydrogen, deuterium, halogen, hydroxyl, —C1-6alkyl, —C1-6alkoxy, —CN, —NRaRb, —C(O)—NRaRb, and —NRa—C(O)—Rb;
- R11, R22 and R33 are independently selected for each occurrence from the group consisting of halogen, hydroxyl, —C1-6alkyl, —C1-6alkoxy, —C3-6cycloalkyl, phenyl, —CN, —CF3 —NRaRb, —C(O)—NRaRb, —NRa—C(O)—Rb, and deuterium;
- wherein —C1-6alkyl and —C1-6alkoxy may optionally be substituted by one or more substituents each independently selected from hydroxyl and halogen;
- and
- Ra and Rb are independently selected for each occurrence from the group consisting of hydrogen and —C1-3alkyl optionally substituted by one or more halogens.
The compound of any of claims 1-4, wherein R3 is selected from the group consisting of
A compound represented by Formula II:
- or a pharmaceutically acceptable salt and/or a stereoisomer thereof, wherein:
- R1 is 5-6 membered heteroaryl containing at least one ring nitrogen;
- wherein R1 may optionally be substituted by one, two or three substituents each independently selected from the group consisting of halogen, hydroxyl, —NH2, —C1-3alkyl, —C1-3alkyl-OH, and —C1-3alkoxy;
- R2 is —C1-6alkyl or —C3-6cycloalkyl;
- wherein R2 may optionally be substituted by one or more substituents each independently selected from the group consisting of halogen, hydroxyl, —C1-3alkyl, —C1-3alkoxy, and —NRaRb;
- and
- Ra and Rb are independently selected for each occurrence from the group consisting of hydrogen and —C1-3alkyl.
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt and/or a stereoisomer thereof.
The method of claim 30, wherein the patient suffering from fibrosis also suffers from systemic sclerosis.
The method of claim 30 or 31, wherein the fibrosis is selected from the group consisting of skin fibrosis, lung fibrosis, and peritoneal fibrosis.
Dependencies are inferred from the claim text.