Novel pharmaceutical compounds
AssigneeConcert Pharmaceuticals, Inc.
InventorRoger Tung
Life of this patent
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Abstract
The present invention relates to derivatives of tadalafil, substituted with fluorine on the methylene carbon atom situated between the oxygens of the benzodioxol ring, and optionally further substituted with deuterium atoms in place of normally abundant hydrogen, and 13C in place of normally abundant 12C. These compounds are selective PDE5 inhibitors and possess advantageous biopharmaceutical and pharmacokinetic properties. The invention further provides compositions comprising these compounds and methods of treating diseases and conditions that are responsive to PDE5 inhibition, alone and in combination with additional agents.
Claims89
An isolated compound of Formula II:
- or a prodrug or a prodrug salt thereof;
- or a hydrate or a solvate or a polymorph of any of the foregoing;
- wherein:
- X1 and X2 are simultaneously fluoro;
- or X1 is deuterium and X2 is selected from hydrogen or deuterium;
- each Y is independently selected from deuterium or hydrogen;
- the hydrogen attached to the indole nitrogen is optionally replaced by deuterium;
- and
- each carbon is independently optionally replaced by 13C.
A compound of formula XIIIa
- wherein:
- D is deuterium;
- Y is selected from hydrogen or deuterium;
- each carbon atom is optionally replaced by 13C;
- and
- each hydrogen atom is optionally replaced by deuterium.
A compound of formula
- wherein:
- X1 and X2 are simultaneously fluoro;
- or X1 is deuterium and X2 is selected from hydrogen or deuterium;
- Y is selected from hydrogen or deuterium;
- E is an ester group labile to ring closure during cyclic amide formation;
- each carbon atom is optionally 13C;
- and
- each hydrogen is optionally replaced by deuterium.
A compound of formula XV:
- wherein:
- X1 and X2 are simultaneously fluoro;
- or X1 is deuterium and X2 is selected from hydrogen or deuterium;
- Z is a leaving group;
- each Y is independently selected from hydrogen or deuterium;
- E is an ester group labile to ring closure during cyclic amide formation;
- the hydrogen attached to each nitrogen is optionally replaced by deuterium;
- and
- each carbon atom is optionally replaced by 13C.
A diagnostic kit comprising, in separate vessels, Compound 1 and a metabolizing enzyme source.
Dependencies are inferred from the claim text.