AZOL COMPOUNDS REPLACED WITH AMIDA

Argentina Patent

APP PUB NO AR-101071-A1
SERIAL NO

P150100940

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Abstract

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Amide substituted azol compounds which are inhibitors of TNKS1 and / or TNKS2, methods for preparing said compounds, intermediates useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and use of said compounds to manufacture a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a single agent or in combination with other active ingredients. Claim 1: A compound characterized in that it is of formula (1) wherein: X¹ represents NR³ or O; X² represents a CR⁶ or N; R¹ represents a group selected from: -OR⁹, and -N (R¹⁰) R¹¹; R² represents a group selected from: hydrogen, C₁₋₃-alkyl, and C₃₋₄-cycloalkyl; R³ represents a hydrogen atom; R⁴ represents a hydrogen atom; R⁵ represents a group selected from: hydrogen, C₁₋₃-alkyl, C₁₋₃-alkoxy, C₁₋₃-haloalkyl, C₁₋₃-haloalkoxy, and halogen; R⁶ represents a group selected from: hydrogen, and halogen; R⁷ represents a hydrogen atom; R⁸ represents a group selected from: aryl, and heteroaryl, where the aryl and heteroaryl groups are optionally substituted with one, two or three substituents, which are independently selected from each other from: C₁₋₆-alkyl, C₁₋₃-alkoxy , C₃₋₆-cycloalkyl, C₃₋₆-cycloalkoxyl, C₁₋₃-haloalkyl, C₁₋₃-haloalkoxy, halogen, cyano, nitro, hydroxyl, (C₁₋₆-alkyl) -S-, (C₁₋₆-alkyl ) -S (= O) -, (C₁₋₆-alkyl) -S (= O) ₂-, -S (= O) (= NR¹⁵R¹⁶), -N (R¹⁰) R¹¹, R¹⁰ (R¹¹) N- ( C₁₋₆-alkyl), R¹⁰ (R¹¹) N- (C₂₋₆-alkoxy) -, phenyl, phenoxy, -N (R¹²) C (= O) R¹³, -C (= O) OH, -C (= O) OR⁹, and -C (= O) N (R¹²) ₂, where two substituents of said aryl group, if they are in ortho position with each other, can be joined together so as to form together metandiylbisoxil, ethan-1,2 -diylbisoxy, propan-1,3-diyl, or butan-1,4-diyl; R⁹ represents a group selected from: C₁₋₆-alkyl, C₃₋₆-cycloalkyl, C₁₋₆-hydroxyalkyl, and (C₁₋₃-alkoxy) - (C₁₋₆-alkyl); R¹⁰ and R¹¹ are independently selected from each other from: hydrogen, C₁₋₆-alkyl, C₃₋₆-cycloalkyl, (C₃₋₆-cycloalkyl) - (C₁₋₆-alkyl), C₂₋₆-hydroxyalkyl, (C₁ ₋₃-alkoxy) - (C₂₋₆-alkyl), C₁₋₆-haloalkyl, H₂N- (C₂₋₆-alkyl), (C₁₋₃-alkyl) N (H) (C₂₋₆-alkyl), ( C₁₋₃-alkyl) ₂N (C₂₋₆-alkyl), HOC (= O) - (C₁₋₆ alkyl), R⁹OC (= O) - (C₁₋₆-alkyl), 4-6 membered heterocycloalkyl, ( 4-6 membered heterocycloalkyl) - (C₂₋₆-alkyl), aryl, heteroaryl, aryl- (C₁₋₆-alkyl), and heteroaryl- (C₁₋₆-alkyl), where the 4-6 membered heterocycloalkyl groups they are optionally substituted with one or two substituents, which are independently selected from each other from: C₁₋₃-alkyl, C₁₋₃-haloalkyl, C₁₋₃-alkoxy, C₁₋₃-haloalkoxy, C₃₋₄-cycloalkyl, C₃ ₋₄-cycloalkoxy, amino, hydroxyl, a halogen atom, and cyano, and, d Where aryl and heteroaryl groups are optionally substituted with one or two substituents, which are independently selected from each other from: C₁₋₃-alkyl, C₃₋₆-cycloalkyl, C₁₋₃-alkoxy, C₃₋₆-cycloalkoxyl, C₁ ₋₃-haloalkyl, C₁₋₃-haloalkoxy, halogen, cyano, -C (= O) OH, -C (= O) OR⁹, and -C (= O) N (R¹²) ₂, or, R¹⁰ and R¹¹ together with the nitrogen atom to which they are attached they form a 4-6 membered heterocycloalkyl group, wherein a carbon atom is optionally replaced by a group containing additional heteroatom selected from NR¹⁴, O, S, S (= O) and S (= O) ₂ where in the heterocycloalkyl group an additional ring atom is optionally replaced by C (= O), where said 4-6 membered heterocycloalkyl group is optionally substituted with one or two substituents, which are independently selected from yes between: C₁₋₃-alkyl, C₁₋₃-haloalkyl, C₁₋₃-alkoxy, C₁₋₃ -haloalkoxy, C₃₋₄-cycloalkyl, C₃₋₄-cycloalkoxy, amino, hydroxyl, a halogen atom, and cyano, or R¹⁰ and R¹¹ together with the nitrogen atom to which they are attached form a group selected from: the group of formulas (2) where * indicates the point of union of said group with the rest of the molecule; R¹² represents a group selected from: hydrogen, and C₁₋₃-alkyl; R¹³ represents a group selected from: hydrogen, C₁₋₆-alkyl, C₁₋₆-hydroxyalkyl, C₃₋₆-cycloalkyl, C₁₋₆-haloalkyl, (C₁₋₃-alkoxy) - (C₁₋₆-alkyl), aryl , and heteroaryl, where the aryl and heteroaryl groups are optionally substituted with one or two substituents, which are independently selected from each other from: C₁₋₃-alkyl, C₃₋₆-cycloalkyl, C₁₋₃-alkoxy, C₃₋₆ -cycloalkoxy, C₁₋₃-haloalkyl, C₁₋₃-haloalkoxy, halogen, cyano, and hydroxyl; R¹⁴ represents a group selected from: hydrogen, C₁₋₃-alkyl, C₁₋₃-haloalkyl, and C₃₋₄-cycloalkyl; R¹⁵ represents a group selected from: hydrogen, cyano, (C₁₋₃-alkyl) -C (= O) -, and (C₁₋₃-haloalkyl) -C (= O) -; R¹⁶ represents a group selected from: C₁₋₄-alkyl, and C₃₋₄-cycloalkyl; or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture thereof. Claim 22: A compound characterized in that it is of the general formula (3), wherein X¹ represents N, and X², R², R⁵ and R⁸ are as defined for the compound of the general formula (1) according to any of the claims 1 to 6. Claim 23: A compound characterized in that it is of the general formula (4), wherein X², R⁵ and R⁸ are as defined for the compound of the general formula (1) according to any one of claims 1 to 6 Claim 24: A compound characterized in that it is of the general formula (5), wherein X¹ represents N, and R¹ and R² are as defined for the compound of the general formula (1) according to any one of claims 1 to 6 Claim 25: A compound characterized in that it is of the general formula (6), wherein X¹ represents N; R¹⁷ represents OR¹⁸; R¹⁸ represents hydrogen or phenyl; and R² is as defined for the compound of general formula (1) according to any one of claims 1 to 6. Claim 26: A compound characterized in that it is of general formula (7), wherein X¹ represents NR³; R¹⁷ represents OR¹⁸; R¹⁸ represents hydrogen or phenyl; and X², R², R³, R⁵ and R⁸ are as defined for the compound of general formula (1) according to any one of claims 1 to 6.

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Patent Owner(s)

Patent OwnerAddress
BAYER PHARMA AGDELEVERKUSEN GERMANY LEVERKUSEN NORTH RHINE-WESTPHALIA

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Inventor(s)

Inventor Name Address
PHILIP DR LIENAU DE
SIMON DR HOLTON DE
KNUT DR EIS DE
JENS DR ACKERSTAFF DE
DETLEV DR SLZLE DE
STEFAN DR GOLZ DE
PHILIPP DR BUCHGRABER DE
VOLKHART MIN DR LI DE
DANIEL DR BASTING DE
FRANZISKA DR SIEGEL DE
MARCUS DR BAUSER DE
JZSEF BALINT DE
MICHAELA DR BAIRLEIN DE
NINGSHU DR LIU DE
ECKHARD JIAN - DR BENDER DE
SARAH WAGNER ALT-STRALAU 52/53 DE

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