Sanofi

Lead Pharma Holding B.v.

Lead Pharma Cel Models IP B.v.

Lead Pharma B.v.

Sander Bernardus Nabuurs

Joseph Maria Gerardus Barbara Cals

David Machnik

Jean-Francois Sabuco

Vera De Kimpe

Joseph Maria Cals

Laurent Schio

Cosimo Damiano Cadicamo

Jaap Gerardus Henricus Lemmers

Jean-François Sabuco

The present application relates to compounds according to (Formula IA) or (Formula IB):  The compounds can be used as inhibitors of ROR&#x3b3; and are useful for the treatment of ROR&#x3b3; mediated diseases.

ROR gamma (ROR&#x3b3;) modulators

Novel compounds according to Formula I or a pharmaceutically acceptable salt thereof wherein: A-Aare N or CR, CR, CR, CR, respectively, with the proviso that no more than two of the four positions A can be simultaneously N; Ris C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino; Ris H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, (3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl; the sulfonyl group with Ris represented by one of R, Ror R; Ris H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl; and Ris C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl. The compounds can be used as inhibitors of ROR&#x3b3; and are useful for the treatment of ROR&#x3b3; mediated diseases.

The present invention relates to compounds according to Formula I: or a pharmaceutically acceptable salt thereof. The compounds can be used as inhibitors of RORy and are useful for the treatment of RORy mediated diseases such as autoimmune and inflammatory diseases. 

ROR gamma (RORy) modulators

Compounds according to Formula I: or a pharmaceutically acceptable salt wherein: Ais NRor CR, with Rherein; the cyclopropyl moiety with one or more methyl and one or more F; A-Aare N or CR-CR, with no more than two of the four positions A in A-Acan be simultaneously N; R-Rare described; Rand Rare independently H, F, methyl, ethyl, hydroxyl or methoxy or Rand Rtogether is carbonyl, all alkyl groups, if substituted with one or more F; Ris H or C(1-6)alkyl; A-Aare N or CR-CR, with no more than two of the four positions A in A-Acan be simultaneously N; R-Rherein; Rand Rherein; or Rand Rfused forming a ring having 5 to 7 atoms by joining Rbeing C(1-6)alkyl or C(2-6)alkenyl. The ROR&#x3b3; compounds can treat ROR&#x3b3; mediated diseases.

Compounds according to Formula I: or a pharmaceutically acceptable salt thereof wherein: Ais NRor CR, with Rbeing H or methyl, with methyl, if present, optionally being substituted with one or more F; the cyclopropyl moiety can be optionally substituted with one or more methyl and one or more F; A-Aare N or CR-CR, respectively, with the proviso that no more than two of the four positions A in A-Acan be simultaneously N; R-Rare independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl; Rand Rare independently H, F, methyl, ethyl, hydroxyl or methoxy or Rand Rtogether is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F; Ris H or C(1-6)alkyl; Ris selected from the group consisting of Formula II, III, IV and V  The compounds can be used as inhibitors of ROR&#x3b3; and are useful for the treatment of ROR&#x3b3; mediated diseases.

Novel compounds according to Formula I Meta or para or a pharmaceutically acceptable salt thereof wherein:A-Aare N or CR, CR, CR, CR, respectively, with the proviso that no more than two of the four positions A in A-Acan be simultaneously N; A, A, A, A, Aare N or CR, CR, CR, CR, CR, respectively, with the proviso that at least one but no more than two of the five positions A in A, A, A, A, Ais N; Ris C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino; Ris H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl; the sulfonyl group with Ris represented by one of R, Ror R; Ris H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl; and Ris C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl.

Aare N or CR, respectively, maximum two of the four positions A simultaneously N; Ris C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(1-6)alkylamino, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino, all alkyl and cycloalkyl group carbon atoms optionally substituted with F and F or methyl, respectively; Rand Rindependently H, F, methyl, ethyl, hydroxy, methoxy or Rand Rtogether is carbonyl, all present alkyl groups optionally substituted with F; Ris H or C(1-6)alkyl; Ris H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with F, Cl, C(1-2)alkyl, C(1-2)alkoxy or cyano; the sulfonyl group with Rrepresented by one of R; the remaining Rare independently H, halogen, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl, all alkyl groups optionally substituted with F; and Rare independently H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl, all groups optionally substituted with F, Cl, C(1-2)alkyl, C(1-2)alkoxy or cyano. 

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Sander Bernardus Nabuurs