IP Library Granted Patent US 9,155,727
Granted Patent B2
US 9,155,727 · App. 14/287,332 · Granted Oct 13, 2015

Chemical compounds

Inventors: Robert Hugh Bradbury (Macclesfield, GB); David Buttar (Macclesfield, GB); Christopher De Savi (Waltham, MA); Craig Samuel Donald (Macclesfield, GB); Richard Albert Norman (Macclesfield, GB); Alfred Arthur Rabow (Macclesfield, GB); Gordon Stuart Currie (Macclesfield, GB); Heather Marie Redfearn (Macclesfield, GB); Nadim Akhtar (Macclesfield, GB); Helen Elizabeth Williams (Macclesfield, GB); Matthew Osborne (Macclesfield, GB); Neda Yavari (Macclesfield, GB)
Assignee: AstraZeneca AB
A61K31/437A61K45/06C07D471/04C07D487/04
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Quick Facts
Patent No.
US 9,155,727
App. No.
14/287,332
Granted
Oct 13, 2015
Kind
B2
Abstract

The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R 1 to R 5 have any of the meanings defined hereinbefore in the description: processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

Claims (28)

1. A compound of the Formula (I)

wherein:

R 1 and R 2 are each independently H or F;

R 3 is H or methyl; and

either:

a) R 4 is H and R 5 is F; or

b) R 4 is F and R 5 is H;

or a pharmaceutically-acceptable salt thereof.

2. A compound as claimed in claim 1 , or a pharmaceutically-acceptable salt thereof, wherein the compound is a compound of formula (IA)

3. A compound as claimed in claim 1 , or a pharmaceutically-acceptable salt wherein R 3 is hydrogen.

4. A compound as claimed in claim 1 , or a pharmaceutically-acceptable salt thereof wherein R 3 is methyl.

5. A compound as claimed in claim 1 , or a pharmaceutically-acceptable salt thereof wherein R 4 is hydrogen and R 5 is fluoro.

6. A compound as claimed in claim 1 , or a pharmaceutically-acceptable salt thereof wherein R 5 is hydrogen and R 4 is fluoro.

7. A compound as claimed in claim 1 or a pharmaceutically-acceptable salt thereof which compound is selected from:

(E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;

(E)-3-(4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;

(E)-3-(3,5-difluoro-4-((1R,3R)-2-((S)-3-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;

(E)-3-(4-((1R,3R)-2-((S)-3-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;

(E)-3-(3,5-difluoro-4-(2-((S)-3-fluoro-2-methylpropyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;

(E)-3-(3,5-difluoro-4-(2-(2-fluoro-2-methylpropyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;

(E)-3-(4-(2-((S)-3-fluoro-2-methylpropyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;

(E)-3-(4-(2-(2-fluoro-2-methylpropyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid;

(E)-3-(3-fluoro-4-(2-((S)-3-fluoro-2-methylpropyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid; and

(E)-3-[4-[(1R,3R)-1-deuterio-2-(2-fluoro-2-methyl-propyl)-3-methyl-4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl]-3,5-difluoro-phenyl]prop-2-enoic acid.

8. A compound as claimed in claim 7 , which is (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid, or a pharmaceutically-acceptable salt thereof.

9. A pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically-acceptable salt thereof, as claimed in claim 1 , and a pharmaceutically-acceptable diluent or carrier.

10. The compound of claim 8 .

11. The pharmaceutically acceptable salt of the compound of claim 8 .

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 9, 2014
From: BRADBURY, ROBERT HUGH; DONALD, CRAIG SAMUEL; NORMAN, RICHARD ALBERT; RABOW, ALFRED ARTHUR; BUTTAR, DAVID; CURRIE, GORDON STUART; REDFEARN, HEATHER MARIE; AKHTAR, NADIM; WILLIAMS, HELEN ELIZABETH; OSBORNE, MATTHEW; YAVARI, NEDA
To: ASTRAZENECA UK LIMITED
Reel/Frame 033919/0913 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 9, 2014
From: DE SAVI, CHRISTOPHER
To: ASTRAZENECA UK LIMITED
Reel/Frame 033919/0957 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 9, 2014
From: ASTRAZENECA UK LIMITED
To: ASTRAZENECA AB
Reel/Frame 033920/0029 →
Continuity (3)
Provisional Application 61827951 · May 28, 2013
Provisional Application 61915685 · Dec 13, 2013
Related Publication 20140357661A1 · Dec 4, 2014