US 9,809,553 B2
Isoquinoline compounds, a process for their preparation, and pharmaceutical compositions containing them
Stéfano Chimenti, Paris (FR); Christine Courchay, Igny (FR); Aimee Dessinges, Rueil Malmaison (FR); Françoise Gellibert, Bures-sur-Yvette (FR); Bertrand Goument, Viroflay (FR); Marc Konnert, Deuil-la-Barre (FR); Jean-Louis Peglion, Le Vesinet (FR); Christophe Poitevin, Paris (FR); Jean-Paul Vilaine, Chatenay Malabry (FR); and Nicole Villeneuve, Rueil Malmaison (FR)
Assigned to LES LABORATOIRES SERVIER, Suresnes (FR)
Appl. No. 15/119,173
Filed by LES LABORATOIRES SERVIER, Suresnes (FR)
PCT Filed Feb. 20, 2015, PCT No. PCT/FR2015/050415
§ 371(c)(1), (2) Date Aug. 16, 2016,
PCT Pub. No. WO2015/124877, PCT Pub. Date Aug. 27, 2015.
Claims priority of application No. 14 51389 (FR), filed on Feb. 21, 2014.
Prior Publication US 2017/0137385 A1, May 18, 2017
Int. Cl. C07D 217/02 (2006.01); C07D 217/04 (2006.01); C07D 405/06 (2006.01); A61K 31/472 (2006.01); C07D 217/24 (2006.01)
CPC C07D 217/02 (2013.01) [C07D 217/24 (2013.01); C07D 405/06 (2013.01)] 20 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Drawing
wherein:
X represents —C(═O), —CH(OH)— or —CH2—,
Ri1 represents a hydrogen atom or a hydroxyl group,
it being understood that the compound of formula (I) wherein Ri1 represents a hydroxyl group may be represented by the following tautomeric form:

OG Complex Work Unit Drawing
Ri2 and Ri3, which may be identical or different, each represent a hydrogen atom, a (C1-C6)alkyl group or a halogen atom,
Ri6, Ri7 and Ri8, which may be identical or different, each represent a hydrogen atom or a halogen atom,
Ra1 and Ra5, which may be identical or different, each represent a hydrogen atom, a halogen atom, an —O(C1-C6)alkyl group or a (C1-C6)alkyl group,
Ra2 represents a hydrogen or halogen atom, a hydroxyl group, a —O(C1-C6)alkyl group, a —(C1-C6)alkyl group, a nitrogen-containing heterocycle having from 3 to 7 ring members, or —O—(CH2)m—NR′R″,
Ra3 represents a hydrogen atom, an —O(C1-C6)alkyl group, a —(C1-C6)alkyl group, a nitrogen-containing heterocycle having from 3 to 7 ring members, or —CRy1Ry2NH(Ry3),
Ra4 represents a hydrogen atom a halogen atom, an —O(C1-C6)alkyl group, a —(C1-C6)alkyl group, or —CRy1Ry2NH(Ry3),
it being understood that:
Ra1, Ra2, Ra3, Ra4 and Ra5 may not simultaneously represent a hydrogen atom,
Ra3 and Ra4 may not simultaneously represent —CRy1Ry2NH(Ry3),
Ra1 and Ra2, together with the carbon atoms carrying them, may form a heterocycle having from 4 to 7 ring members chosen from tetrahydrofuran, 1,4-dioxane, tetrahydropyran, tetrahydro-2H-pyran-4-amine and 1-(tetrahydro-2H-pyran-4-yl)methanamine, and
Ra2 and Ra3, together with the carbon atoms carrying them, may form a hydrocarbon ring having from 4 to 7 ring members chosen from cyclopentane, cyclopentanamine, N-cyclopentylglycinamide and 1-methylcyclopentanamine,
m is an integer, the value of which is fixed at 1, 2 or 3,
R′ and R″, which may be identical or different, each represent —(C1-C6)alkyl groups or, together with the nitrogen atom carrying them, form a heterocycle having from 3 to 7 ring members,
Ry1 represents a hydrogen atom, a —(C1-C6)alkyl group, a —CH2-cyclohexyl group, or a 3-methoxyphenyl group,
Ry2 represents a hydrogen atom or a —(C1-C6)alkyl group,
Ry3 represents:
a hydrogen atom,
—C(═O)—CHRy4-NHRy5 wherein Ry4 represents a hydrogen atom or a (C1-C6)alkyl group and Ry5 represents a hydrogen atom or a methyl group, or
a —(C1-C6)alkyl group which may be substituted by a hydroxyl group, an —O(C1-C3)alkyl group, a cyclohexyl group or a methylsulphonyl group,
or Ry1 and Ry2, together with the carbon atom carrying them, form a cyclopropane, cyclobutane or tetrahydropyran group,
or Ry2 and Ry3, together with the carbon and nitrogen atoms carrying them, respectively, form a pyrrolidine or piperidine group,
or an optical isomer thereof, where it exists, an addition salt thereof with a pharmaceutically acceptable acid or a hydrate thereof.