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US 2023/0150931 A1Published application
Fabp4/5 inhibitors, methods of use and methods of making
AssigneeNovius Therapeutics, LLC
InventorsLiraz Levi, Tej Pareek, Elizabeth Meyers, Seunghwan Lim, William J. Greenlee, Seong-Jin Kim
Life of this patent
Estimating the term…
Abstract
Disclosed herein are FABP4 and FABP5 inhibitor compounds and their use in pharmaceutical compositions for treating diseases relating to fatty acid metabolism, including cancer. Also disclosed herein are methods for preparing the disclosed compounds.
Claims44
A compound of structural formula I:
- wherein R7, R8, R9, R10, and R11 is each independently selected from hydrogen or a substitution for hydrogen;
- wherein X has the formula:
- wherein Y is —CR5R6—, or a heteroatom selected from —S—, —O—, —SO—, and —SO2—;
- and R5 and R6 are each independently selected from hydrogen, C1-C4 linear or branched alkyl, phenyl, and benzyl;
- wherein R1, R2, R3 and R4 is each independently selected from hydrogen, C1-C4 linear or branched alkyl, phenyl, and benzyl, R1 and R4 can be taken together to form a carbocyclic or heterocyclic ring containing from 5 to 6 atoms, or when Y is a carbon atom R5 and R6 can be taken together with the Y unit to form a ring having from 4 to 7 atoms;
- or a pharmaceutically acceptable salt thereof;
- with the provisos that:
- (i) when Y is —S—, R1, R2, R3, R4, R8, and R11 are hydrogen, and R7 and R9 are Cl, R10 is not isopropoxy, benzyloxy, prop-2-yn-1-yloxy, 2-methoxy, 2-methoxyethoxy, 2-ethoxy-2-oxoethoxy;
- and
- (ii) when Y is —O—, R1, R2, R3, R4, R8, and R11 are hydrogen, and R7 and R9 are Cl, R10 is not hydrogen, or 2-methoxyethoxy.
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A pharmaceutical composition, comprising:
- (a) from about 10% to about 95% by weight of one or more compounds of structural formula I:
- wherein R7, R8, R9, R10, and R11 are each independently selected from hydrogen or a substitution for hydrogen;
- X has the formula:
- wherein Y is —CR5R6—, or a heteroatom selected from —S—, —O—, —SO—, and —SO2—;
- and R5 and R6 are each independently selected from hydrogen, C1-C4 linear or branched alkyl, phenyl, and benzyl;
- wherein R1, R2, R3 and R4 is each independently selected from hydrogen, C1-C4 linear or branched alkyl, phenyl, and benzyl, R1 and R4 can be taken together to form a carbocyclic or heterocyclic ring containing from 5 to 6 atoms, or when Y is a carbon atom R5 and R6 can be taken together with the Y unit to form a ring having from 4 to 7 atoms;
- and
- (b) one or more adjunct ingredients.
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A method for treating a subject having a disease or condition affected by FABP4/5, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising one or more compounds of structural formula I:
- wherein R7, R8, R9, R10, and R11 is each independently selected from hydrogen or a substitution for hydrogen;
- wherein X has the formula:
- wherein Y is —CR5R6—, or a heteroatom selected from —S—, —O—, —SO—, and —SO2—;
- and R5 and R6 are each independently selected from hydrogen, C1-C4 linear or branched alkyl, phenyl, and benzyl;
- wherein R1, R2, R3 and R4 is each independently selected from hydrogen, C1-C4 linear or branched alkyl, phenyl, and benzyl, R1 and R4 can be taken together to form a carbocyclic or heterocyclic ring containing from 5 to 6 atoms, or when Y is a carbon atom R5 and R6 can be taken together with the Y unit to form a ring having from 4 to 7 atoms;
- or
- a pharmaceutically acceptable salt thereof.
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A process for preparing a compound of structural formula III:
- wherein Y is —CR5R6—, or a heteroatom selected from —S—, —O—, —SO—, and —SO2—;
- and R5 and R6 are each independently selected from hydrogen, C1-C4 linear or branched alkyl, phenyl, and benzyl;
- wherein R1, R2, R3 and R4 is each independently selected from hydrogen, C1-C4 linear or branched alkyl, phenyl, and benzyl, R1 and R4 can be taken together to form a carbocyclic or heterocyclic ring containing from 5 to 6 atoms, or when Y is a carbon atom R5 and R6 can be taken together with the Y unit to form a ring having from 4 to 7 atoms;
- wherein R7, R8, R9, R10, and R11 is each independently selected from:
- i) hydrogen;
- ii) halogen;
- iii) C1-C4 linear or branched, saturated or unsaturated alkyl;
- iv) C1-C4 linear or branched, saturated or unsaturated alkoxy;
- v) —(CR12aR12b)qOR13;
- vi) —(CR12aR12b)qC(O)R13;
- vii) —(CR12aR12b)qC(O)OR13;
- viii) —O(CR12aR12b)qC(O)OR13;
- ix) —(CR12aR12b)qN(R13)2;
- x) —CHmXn;
- wherein X is halogen, m is from 0 to 2, m+n=3;
- xi) —(CR12aR12b)qCN;
- and
- xii) —(CR12aR12b)qNO2;
- wherein each R13 is independently hydrogen, C1-C4 linear or branched alkyl, phenyl, or benzyl;
- and wherein R12a and R12b are each independently hydrogen, methyl or ethyl, and the index q is an integer from 0 to 4;
- the process comprising:
- (a) combining in a solvent a compound having the formula:
- wherein R1, R2, R3 and R4 are as defined above;
- with a compound having the formula:
- wherein R7, R8, R9, R10, and R11 are as defined above;
- and
- (b) removing the solvent.
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Dependencies are inferred from the claim text.