Pyrazole derivatives and their use as protein kinase inhibitors

Details Pyrazole derivatives and their use as protein kinase inhibitors Pyrazole derivatives and their use as protein kinase inhibitors

C - Chemistry, Metallurgy

07

D

C07D 231/40 (2006.01) A61K 31/415 (2006.01) A61P 25/00 (2006.01) C07D 231/38 (2006.01) C07D 401/12 (2006.01) C07D 403/12 (2006.01) C07D 405/04 (2006.01) C07D 413/08 (2006.01) C07D 417/06 (2006.01)

Patent

CA 2420363

The invention provides compounds of formula (1) wherein R1, R2, R3, and R4 are as defined, and their pharmaceutically acceptable salts. Compounds of formula (1) are indicated to have activity inhibiting cdk2, and GSK-3. Pharmaceutical compositions and methods comprising compounds of formula (1) for treating and preventing diseases and conditions comprising abnormal cell growth, such as cancer, and neurodegenerative diseases and conditions and those affected by dopamine neurotransmission. Also described are pharmaceutical compositions and methods comprising compounds of formula (1) for treating male fertility and sperm motility; diabetes mellitus; impaired glucose tolerance; metabolic syndrome or syndrome X; polycystic ovary syndrome; adipogenesis and obesity; myogenesis and frailty, for example age-related decline in physical performance; acute sarcopenia, for example muscle atrophy and/or cachexia associated with burns, bed rest, limb immobilization, or major thoracic, abdominal, and/or orthopedic surgery; sepsis; hair loss, hair thinning, and balding; and immunodeficiency.

L'invention concerne des composés correspondant à la formule (1), ainsi que des sels de ceux-ci, acceptables sur le plan pharmacologique. Dans cette formule R?1¿, R?2¿, R?3¿, et R?4¿ possèdent les notations données dans la description. Ces composés correspondant à la formule (1) sont indiqués comme possédant une activité d'inhibition de cdk5, cdk2 et GSK-3. L'invention concerne également des compositions pharmaceutiques comprenant ces composés, ainsi que des procédés mettant en oeuvre ces composés pour traiter et prévenir des maladies et pathologies comprenant une croissance cellulaire anormale, telles que le cancer, et les maladies et pathologies neurodégénératives, ainsi que celles concernées par la neurotransmission de la dopamine. L'invention concerne encore des compositions pharmaceutiques comprenant ces composés, ainsi que des procédés mettant en oeuvre ces composés pour traiter la fertilité mâle et la motilité des spermatozoïdes, le diabète sucré, la tolérance au glucose altérée, le syndrome métabolique ou syndrome X, la polykystose ovarienne, l'adipogenèse et l'obésité, la myogenèse et la fragilité -par exemple le déclin des performances physiques associé à l'âge-, la sarcopénie aiguë -par exemple l'atrophie musculaire et/ou la cachexie associée à des brûlures, à l'alitement, à l'immobilisation des membres, ou à une importante chirurgie thoracique, abdominale et/ou orthopédique-, à la septicémie, à la perte de cheveux, à la chute des cheveux et à la calvitie, ainsi qu'au déficit immunitaire.

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