US 2008/0167332 A1 · Novel Compounds 243

Abstract

Compounds of formula (I) wherein R1, R3, R4, R5, R6, R7, and R10 are as defined in the specification, are described. The present invention also relates to pharmaceutical composition comprising said compounds and to the use of said compounds in therapy. The present invention further relates to processes for the preparation of said compounds and to new intermediates useful in the preparation thereof. Beside, the invention relates to salts and polymorphic forms of the new compounds as well as the preparation thereof.

Claims67

Dependent claims

A compound of formula

wherein:
R1 is halogen;
R3 is hydrogen or hydroxyl;
R10 is hydrogen or C1-3alkyl;
R4 is —CONR8R9, —N(H)C(O)R11 or —N(H)C(O)NR8R9, where R8 and R9 are independently selected from hydrogen, C1-6 alkyl or C3-7cycloalkyl, or
R8 and R9 together with the nitrogen atom to which they are attached, form a 4-7 membered heterocyclic ring which is optionally substituted with one or more hydroxy groups;
R11 is C1-6alkyl, C2-6alkenyl, C3-6cycloalkyl, adamantyl, C5-6cycloalkenyl, phenyl or a saturated or unsaturated 5-10 membered heterocyclic ring system comprising at least one heteroatom selected from nitrogen, oxygen, and sulphur, each of which may be optionally substituted by one or more substituents independently selected from nitro, hydroxyl, oxo, halo, carboxyl, C1-6 alkyl, C1-6alkoxy, C1-6alkylthio, C1-6alkycarbonyl, C1-6alkoxycarbonyl, phenyl or —NHC(O)R2;
R2 is C1-6alkyl, amino or phenyl;
R5 is hydrogen or halo;
R6 and R7 are independently selected from hydrogen or C1-6alkyl, or
R6 and R7 together with the carbon atom to which they are attached form a 3-7 membered saturated cycloalkyl group, or a pharmaceutically acceptable salt thereof.

8 more elements

A compound selected from:

(4-(acetylamino)-2-chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}phenoxy)acetic acid;
(4-(acetylamino)-3-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}phenoxy)acetic acid;
(4-(acetylamino)-2-chloro-5-{[(2S)-3-(5-fluoro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}phenoxy)acetic acid;
{2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(methylamino)carbonyl]phenoxy}acetic acid;
2-{2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(methylamino)carbonyl]phenoxy}-2-methylpropanoic acid;
{2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(dimethylamino)carbonyl]phenoxy}acetic acid;
2-{2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(dimethylamino)carbonyl]phenoxy}-2-methylpropanoic acid;
(2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-{[(3)-3-hydroxypyrrolidin-1-yl]carbonyl}phenoxy)acetic acid;
2-{2-Chloro-5-{[(2R)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(methylamino)carbonyl]phenoxy}-2-methylpropanoic acid;
2-{2-Chloro-5-{3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(dimethylamino)carbonyl]phenoxy}-2-methyl-propanoic acid;
and
2-[5-{[(2S)-3-(7-tert-Butyl-5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-2-chloro-4-(methylcarbamoyl)phenoxy]-2-methylpropanoic acid, or a pharmaceutically acceptable salt thereof.

9 more elements

A compound selected from:

(4-(acetylamino)-2-chloro-5-{[(2S)-3-(5-fluoro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}phenoxy)acetic acid, hydrochloride;
2-{2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(methylamino)carbonyl]phenoxy}-2-methylpropanoic acid sodium hydroxide;
2-{2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(dimethylamino)carbonyl]phenoxy}-2-methylpropanoic acid hydrochloride;
2-{2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(dimethylamino)carbonyl]phenoxy}-2-methyl-propanoic acid trifluoracetate;
2-{2-Chloro-5-{[(2S)-3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(dimethylamino)carbonyl]phenoxy}-2-methyl-propanoic acid p-toluensulfonat;
2-{2-Chloro-5-{3-(5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-4-[(dimethylamino)carbonyl]phenoxy}-2-methyl-propanoic acid trifluoracetate;
and
2-[5-{[(2S)-3-(7-tert-Butyl-5-chloro-1′H,3H-spiro[1-benzofuran-2,4′-piperidin]-1′-yl)-2-hydroxypropyl]oxy}-2-chloro-4-(methylcarbamoyl)phenoxy]-2-methylpropanoic acid trifluoroacetate.

5 more elements

Dependencies are inferred from the claim text.

Novel Compounds 243

Life of this patent

Novel Compounds 243

Life of this patent

Abstract

Claims67