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1. (WO2017093938) TETRAHYDROISOQUINOLINE DERIVATIVES
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

 

What is claimed is:

1. A compound of Formula I:

Formula I

wherein:

each Y is independently C=O, CH-R6, or N-L-R3 R3 with the proviso that at least one Y must be CH-R6;

X is O or CH2;

R1 is C1-6alkyl wherein said alkyl may contain cycloalkyl portions;

W is a bond, -CH=CH-, -C=C-, C1-3alkylene, -CH2C(O)NH-, -NHC(O)-, -N(CH3)C(O)-, -N(CH3)C(O)CH2-, -C(O)-, -CH2(CO)-, or -NHC(O)CH2-, wherein each W is optionally substituted by 1 or 2 methyl groups;

R2 is H, C1-6alkyl, C5-14aryl, C3-7cycloalkyl, C3-7cycloalkenyl, C3-9heterocycle, or C5- 9heteroaryl, wherein each R2 group is optionally substituted by one to four substituents selected from halo, C1-6alkyl, C1-6hetereoalkyl, or C1-6alkylene or C1-6hetereoalklylene wherein said C1-6alkylene or C1-6hetereoalklylene is bonded to adjacent carbon atoms on said C5-14aryl, C3-7cycloalkyl, C3-7cycloalkenyl, C3-9heterocycle, or C5-9heteroaryl to form a fused ring;

each L is independently a bond, -CH2(CO)-, -C1-3alkylene-, -SO2-, -C(O)-, -C(S)-, -C(NH)-, -C(O)NH-, -C(O)NHCH2-,-C(O)N-, -C(O)OCH2-, -C(O)O-, -C(O)C(O)-, -SO2-NH- , or–CH2C(O)-;

each R3 is independently H, CN, oxo, C1-6alkyl, C5-14aryl, CH2C5-14aryl, CH2C3- 7cycloalkyl, C3-7cycloalkyl, C3-7spirocycloalkyl, C3-7cycloalkenyl, C3-9heterocycle, or C5- 9heteroaryl, or an R3 may join together with an R6 or an R3 to form a fused 5-7 membered ring, and wherein each R3 group is optionally substituted by one to four substituents selected from halo, oxo, C1-6alkyl, C3-7cycloalkyl, C1-3fluoroalkyl, -OC1-6alkyl, -C(O)R4, -C(O)NR4, -C(O)NHR4, C5-14aryl, C1-6hetereoalkyl, -B(OH)2, C3-9heterocycle, C5-9heteroaryl,

 

 

-C(O)OC1-6alkyl, or two substituents may bond together to form a fused, spiro, or bridged ring and that fused, spiro, or bridged ring may optionally be substituted with R4;

R4 is CN, halo, -OC1-6alkyl, C1-6alkyl, C3-7cycloalkyl, C3-9heterocycle, or C5-14aryl; each R5 is independently H, C1-3alkyl, C3-6cycloalkyl, CH2F, CHF2, or CF3;

each R6 is independently H, oxo, C1-3alkyl, C5-14aryl, C3-9heterocycle, C5-9heteroaryl, -C(O)NR4, or -C(O)NHR4, or both R6 may together comprise 2-4 carbon atoms and join together to form a bridged ring system, or R6 may represent a gem di-C1-3alkyl;

and wherein each heterocycle, heteroaryl, heteroalkyl, and heteroalkylene comprises one to three heteroatoms selected from S, N, B, or O.

2. A compound according to Claim 1 wherein R1 is C1-6alkyl.

3. A compound according to Claim 1 or Claim 2 wherein W is a bond.

4. A compound according to any of Claims 1-3 wherein each R6 is H.

5. A compound according to any of Claims 1-4 wherein R2 is optionally substituted phenyl.

6. A compound according to Claim 5 wherein R2 is phenyl substituted by one to four substituents selected from fluorine, methyl, -CH2CH2CH2O- wherein said -CH2CH2CH2O- is bonded to adjacent carbon atoms on said phenyl to form a bicyclic ring, or -NHCH2CH2O-wherein said -NHCH2CH2O- is bonded to adjacent carbon atoms on said phenyl to form a bicyclic ring.

7. A compound according to any of Claims 1-6 wherein each R3 is independently C1-6alkyl, phenyl, naphthyl, cyclopentyl, cyclohexyl, pyridyl, or tetrahydropyranyl, each of which is optionally substituted by 1-3 substituents selected from halogen, C1-6alkyl, -OC1-6alky, C1- 3fluoroalkyl, or phenyl.

8. A compound according to any of Claims 1-7 wherein each R5 is methyl.

9. A compound according to any of Claims 1-8 wherein X is O.

10. A compound according to any of Claims 1-9 wherein one Y group is N-L-R3.

 

 

11. A compound according to any of Claims 1-10 wherein the stereochemistry on the carbon to which XR1 is bound is as depicted below.

12. A pharmaceutically acceptable salt of a compound according to any of Claims 1-11.

13. A pharmaceutical composition comprising a compound or salt according to any of Claims 1-12.

14. A method for treating a viral infection in a patient mediated at least in part by a virus in the retrovirus family of viruses, comprising administering to said patient a composition according to Claim 13.

15. The method of Claim 14 wherein said viral infection is mediated by the HIV virus.

16. A compound or salt as defined in any of Claims 1-12 for use in medical therapy.

17. A compound or salt as defined in any of Claims 1-12 for use in the treatment of a viral infection in a human.

18. The use of a compound or salt as defined in any of Claims 1-12 in the manufacture of a medicament for use in the treatment of a viral infection in a human.