CARMELID CAPALDI,MAURO RICCABONI,HERV VAN DE POL,RENATO DE FANTI,ELISABETTA ARMANI,GABRIELE AMARI,CHARLES BAKER-GLENN
申请号：
ARP140104521
公开号：
AR098622A1
申请日:
2014.12.04
申请国别(地区):
AR
年份:
2016
代理人:
摘要：
Compounds with a benzhydryl structure that can act as inhibitors of the enzyme phosphodiesterase 4 (PDE4) and also as antagonists of muscarinic M3 receptors, with methods to prepare them, with compositions that comprise them and with their use in therapy, in the treatment of chronic obstructive pulmonary disease (COPD). Claim 1: A compound characterized in that it is of general formula (1) where each R¹ is hydrogen or is selected from the group consisting of: halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, hydroxy, -SO₂NR⁶R⁷ ,-Cn, - No. 831222； - No. 183228313；-8310； 8311；-CONR⁶R⁷ and -NR⁸COR⁹ and wherein said C₁₋₄ alkyl is optionally substituted with one or more groups selected from C₃₋₇ cycloalkyl, hydroxy and -NR⁶R⁷ and where said C₁₋₄ alkoxy is optionally substituted with one or more halogens or C₃₋ groups ₇ cycloalkyl where, R⁶ is hydrogen or C₁₋₆ alkyl； R⁷ is hydrogen or C₁₋₆ alkyl； R⁸ is hydrogen or C₁₋₆ alkyl； R⁹ is hydrogen or C₁₋₆ alkyl； n is an integer in the range 1 to 3； each R² is hydrogen or is selected from the group consisting of: halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, hydroxy, -SO₂NR¹⁰R¹¹,-CN and -NR¹²SO₂R¹³ and where said C₁₋₄ alkyl and said C₁₋₄ alkoxy are optionally substituted with a C₃₋₇ cycloalkyl group, where R¹⁰ is hydrogen or C₁₋₆ alkyl； R¹¹ is hydrogen or C₁₋₆ alkyl； R¹² is hydrogen or C₁₋₆ alkyl； R¹³ is hydrogen or C₁₋₆ alkyl； m is an integer in the range between 1 and 3； R³ and R⁴ are different or the same and are independently selected from the group consisting of: H； C₃₋₇ cycloalkylcarbonyl； C₁₋₆ alkyl, optionally substituted with one or more substituents selected from C₃₋₇ cycloalkyl or C₅₋₇ cycloalkenyl； C₁₋₆ haloalkyl；C₃₋₇ cycloalkyl； C₅₋₇ cycloalkenyl； C₂₋₆ alkenyl； and C₂₋₆ alkynyl； or R³ and R⁴,Together with the interconnected atoms, they form a formula (2) ring of 2,2-fluoro-1,3-nitrogen dioxide, which is combined with the phenyl units of the binding group - or - and - or83088.The asterisk indicates the carbon atom
