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1. WO2020112700 - DÉRIVÉS AMINO TRIAZOLO QUINAZOLINE 9-SUBSTITUÉS UTILES EN TANT QU'ANTAGONISTES DU RÉCEPTEUR DE L'ADÉNOSINE, COMPOSITIONS PHARMACEUTIQUES ET LEUR UTILISATION

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]
WHAT IS CLAIMED IS:

1. A compound having a structural Formula (I):


or a pharmaceutically acceptable salt thereof, wherein:

R1 is selected from F, Cl, (Ci-Ce)alkyl, and 0(Ci-Ce)alkyl;

R2 is selected from H, F, Cl, (Ci-Ce)alkyl, and 0(Ci-C6)alkyl;

ring A is a moiety selected from:


R3 is selected from pyrazolyl, triazolyl, and pyridinyl, wherein said pyrazolyl and said triazolyl, are substituted with 1 or 2 R3A groups, and wherein said pyridinyl is substituted with 1, 2, or 3 R3A groups, wherein:

each R3A is independently selected from (Ci-C6)alkyl, 0(Ci-C6)alkyl, (Ci-Ce)alkyl-OH, (Ci-C6)haloalkyl, 0(Ci-C6)haloalkyl, oxo, (Ci-C4)alkylC(0)(Ci-C )alkyl, (Ci- C4)alkylCH(OH)(Ci-C3)alkyl, (Ci-C4)alkylS(0)2(Ci-C3)alkyl, -(CH2)n(C3-C7)cycloalkyl, and -(CH2)n4-7 membered monocyclic heterocycloalkyl comprising 1 or 2 ring heteroatoms selected from oxygen and nitrogen, wherein said (C3-C7)cycloalkyl, and said 4-7 membered monocyclic heterocycloalkyl are each unsubstituted or substituted with 1, 2, or 3 groups independently selected from F, Cl, OH, (Ci-C6)alkyl, and (Ci-C6)haloalkyl;

n is 0, 1, or 2;

RA1 is selected from H, and (Ci-C4)alkyl;

RA2 is selected from H, F, and (Ci-C4)alkyl;

RA3 is selected from H, F, and (Ci-C4)alkyl;

RA4 is selected from H and OH; and

RA5 is selected from H, F, and (Ci-C4)alkyl.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from F, Cl, and OCH3; and

R2 is selected from H, F, Cl, CH3, and OCH3.

3. The compound of any of claims 1 or 2, or a pharmaceutically acceptable salt thereof, wherein:

ring A is a moiety selected from:


wherein:

each R3A is a moiety selected from:

and

each R3Aa is independently selected from (Ci-C4)alkyl, 0(Ci-C4)alkyl, (Ci-C4)haloalkyl, and 0(Ci-C4)haloalkyl.

4. The compound of any of claims 1 or 2, or a pharmaceutically acceptable salt thereof, wherein

ring A is the moiety:


wherein:

each R3A is a moiety selected from:

and

each R3Aa is independently selected from (Ci-C4)alkyl, 0(Ci-C4)alkyl, (Ci-C4)haloalkyl, and 0(Ci-C4)haloalkyl.

5. The compound of any of claims 1 or 2, or a pharmaceutically acceptable salt thereof, wherein:

ring A is the moiety:


wherein:

each R3A is a moiety selected from:

and

each R3Aa is independently selected from (Ci-C4)alkyl, 0(Ci-C4)alkyl, (Ci-C4)haloalkyl, and 0(Ci-C4)haloalkyl.

6. The compound of any of claims 1 or 2, or a pharmaceutically acceptable salt thereof, wherein:

ring A is the moiety:


wherein:

each R3A is a moiety selected from:

and

each R3Aa is independently selected from (Ci-C4)alkyl, 0(Ci-C4)alkyl, (Ci-C4)haloalkyl, and 0(Ci-C4)haloalkyl.

7. The compound of any of claims 1 or 2, or a pharmaceutically acceptable salt thereof, wherein:

ring A is the moiety:


wherein:

each R3A is a moiety selected from:


and

each R3Aa is independently selected from (Ci-C4)alkyl, 0(Ci-C4)alkyl, (Ci-C4)haloalkyl, and 0(Ci-C4)haloalkyl.

8. The compound of any of claims 1 or 2, or a pharmaceutically acceptable salt thereof, wherein:

ring A is the moiety:


wherein:

each R3A is a moiety selected from:


and each R3Aa is independently selected from (Ci-C4)alkyl, 0(Ci-C4)alkyl, (Ci- C4)haloalkyl, and 0(Ci-C4)haloalkyl.

9. The compound of any of claims 1 or 2, or a pharmaceutically acceptable salt thereof, wherein:

ring A is the moiety:

wherein:

each R3A is a moiety selected from:


each RAa is independently selected from (Ci-C4)alkyl, 0(Ci-C4)alkyl, (Ci-C4)haloalkyl, and 0(Ci-C4)haloalkyl;

10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from:













11. A pharmaceutical composition comprising a compound of any of claims 1 to 10, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

12. A method of treating cancer comprising administering an effective amount of a compound of any of Claims 1 to 10, or a pharmaceutically acceptable salt thereof, to a person in need thereof.

13. The method of claim 12, wherein said cancer is selected from melanoma, head & neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, gastric cancer, cervical cancer, primary mediastinal large-B-cell lymphoma, microsatellite instability-high cancer, non-small cell lung cancer, hepatocellular carcinoma, clear cell kidney cancer, colorectal cancer, breast cancer, squamous cell lung cancer, basal carcinoma, sarcoma, bladder cancer, endometrial cancer,

pancreatic cancer, liver cancer, gastrointestinal cancer, multiple myeloma, renal cancer, mesothelioma, ovarian cancer, anal cancer, biliary tract cancer, esophageal cancer, salivary cancer, and prostate cancer, and metastatic castration resistant prostate cancer.

14. The method of claim 13, wherein said compound, or a pharmaceutically acceptable salt thereof, is administered in combination with another therapeutic agent.

15. The method of claim 14, wherein said additional therapeutic agent is a PD-1 antagonist.

16. The method of claim 15, wherein said additional therapeutic agent is selected from pembrolizumab nivolumab, atezolizumab, dunvalumab, and avelumab.

17. The method of claim 15, wherein said additional therapeutic agent is pembrolizumab.