Cyclopropane compounds and pharmaceutical use thereof

The present invention provides a compound having aggrecanase inhibitory activity and MMP-13 inhibitory activity, and useful as a therapeutic agent for osteoarthritis, rheumatoid arthritis and the like, more specifically, a cyclopropane compound of formula (1): wherein R1 is -(CH2)m-X-(CH2)n-A1 etc.,...

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Hauptverfasser: YOSHIKAZU HORI, TAKAFUMI MATSUO, TAMOTSU NEGORO, ELLEN R. LAIRD, ANDREW M. FRYER, YUICHI SHINOZAKI, TAKASHI INABA, AKIRA SUMA, NICOLE M. LITTMAN, ATUSHI SAKAI, MAKOTO SHIOZAKI, STEVEN W. ANDREWS, KATSUTAKA YASUE, JULIA HAAS, HIROTO IMAI
Format: Patent
Sprache:eng
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Zusammenfassung:The present invention provides a compound having aggrecanase inhibitory activity and MMP-13 inhibitory activity, and useful as a therapeutic agent for osteoarthritis, rheumatoid arthritis and the like, more specifically, a cyclopropane compound of formula (1): wherein R1 is -(CH2)m-X-(CH2)n-A1 etc., wherein m and n are the same or different and each is 0 to 6, X is a single bond, etc. and A1 is a substituted C3-14 hydrocarbon ring group, etc.; R2 and R3 are the same or different and each is a hydrogen atom, -(CH2)p-X1-(CH2)q-A2, etc., wherein p and q are the same or different and each is 0 to 6, X1 is a single bond, etc. and A2 is an optionally substituted C3-14 hydrocarbon ring group, etc.; R4 is -CO2R9, etc., wherein R9 is a hydrogen atom, etc.; and R20 and R21 are the same or different and each is a hydrogen atom, -(CH2)m12-X12-(CH2)m12-R30, etc., wherein m12 and m12 are the same or different and each is 0 to 6, X12 is a single bond, etc. and R30 is a hydrogen atom, etc.; or a prodrug thereof or a pharmaceutically acceptable salt thereof.