148 results about "Cyclin-dependent kinase" patented technology

The present invention relates to novel compounds for the inhibition of cyclin-dependent kinases, and more particularly, to chromenone derivatives of formula (Ic)

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇ and A have the meanings indicated in the claims. The invention also relates to processes for the preparation of the compounds of formula (Ia), to methods of inhibiting cyclin-dependent kinases and of inhibiting cell proliferation, to the use of the compounds of formula (Ic) in the treatment and prophylaxis of diseases, which can be treated or prevented by the inhibition of cyclin-dependent kinases such as cancer, to the use of the compounds of formula (Ic) in the preparation of medicaments to be applied in such diseases. The invention further relates to compositions containing a compound of formula (Ic) either alone or in combination with another active agent, in admixture or otherwise in association with an inert carrier, in particular pharmaceutical compositions containing a compound of formula (Ic) either alone or in combination with another active agent, together with pharmaceutically acceptable carrier substances and auxiliary substances.

The invention searches the novel micromolecule inhibitor pyrazolo (1, 5-a) miazines compounds of cyclin-dependent kinase CDK9 (cyclin-dependent kinase) through the virtual screening of a computer, biometrically measures activity thereof, and validates interaction mechanism. The invention specifically comprises the following steps: the three-dimensional crystal conformation of the cyclin-dependent kinase family member CDK9 is obtained in a way of homology modeling; and micromolecule three-dimensional database is screened with DOCK (molecular docking). The invention uses a MTT tumor cell growth inhibition test to biometrically measures the activity of the selected compounds, researches the selected compounds pyrazolo (1, 5-a) miazines with high activety in a way of molecular mechanism, validates the inhibiting effect of the compounds to the activity of CDK9 kinase, and clarifies the interaction mechanism of the compounds for inhibiting the external activity and the molecule of various malignancies such as lung cancer, osteosarcoma, oophoroma, cervical carcinoma, breast cancer, etc.

The present invention relates to methods of suppressing neuronal death, such as is observed with ischemia-related diseases and disorders, including neuronal and cardiac conditions arizing from a sudden loss of oxygen and/or energy loss, and degenerative diseases, such as Alzheimer's disease to name just one. The methods involve the use of inhibitors that act primarily in a simultaneous manner on the cyclin-dependent kinases, CDK4 and CDK6.

The invention discloses a goat CDK2 (Cyclin-dependent kinases 2) gene knockout vector and a construction method thereof. A CRISPR/Cas9 system is adopted; an SgRNA segment of a CDK2 gene is designed at first and an SgRNA nucleotide sequence is synthesized; a plasmid PYSY-sgRNA for expressing SgRNA and Cas9D10A at the same time is constructed; the plasmid PYSY-sgRNA is connected and transformed to an escherichia coli DH5alpha competent cell; finally, a transformant is verified; restriction enzyme digestion and sequencing identification prove that the construction of the CDK2 gene knockout vector is accurate. The vector constructed by CRISPR/Cas9 is adopted, and a theoretical basis is provided for subsequently obtaining a goat CDK2 gene deletion type cell line and researching a molecular mechanism of cell apoptosis molecules triggered by mycoplasma pneumonia infection.

The present invention relates to novel compounds for the inhibition of cyclin-dependent kinases, and more particularly, to chromenone derivatives of formula (Ia),

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇ and A have the meanings indicated in the claims. The invention also relates to processes for the preparation of the compounds of formula (Ia), to methods of inhibiting cyclin-dependent kinases and of inhibiting cell proliferation, to the use of the compounds of formula (Ia) in the treatment and prophylaxis of diseases, which can be treated or prevented by the inhibition of cyclin-dependent kinases such as cancer, to the use of the compounds of formula (Ia) in the preparation of medicaments to be applied in such diseases. The invention further relates to compositions containing a compound of formula (Ia) either alone or in combination with another active agent, in admixture or otherwise in association with an inert carrier, in particular pharmaceutical compositions containing a compound of formula (Ia) either alone or in combination with another active agent, together with pharmaceutically acceptable carrier substances and auxiliary substances.

The present invention provides methods and compositions for modulating the phosphorylation of DARPP-32 in a serotonergic receptor intracellular signaling pathway. The invention provides methods and compositions for modulating the activities of DARPP-32, casein kinase 1 (CK1), cyclin-dependent kinase 5 (Cdk5), AMPA receptors, protein phosphatase-1 (PP-1), protein phosphatase 2C (PP2C), protein phosphatase 2B (PP2B) and/or protein phosphatase 2A (PP2A) in cells or tissues. The invention provides methods of treating serotonergic intracellular signaling pathway disorders, e.g., depression. The invention provides methods of treating dopamine-related disorders. The invention provides methods of identifying agents that modulate the activities of serotonergic receptor intracellular signaling molecules, DARPP-32, casein kinase 1, cyclin-dependent kinase 5, AMPA receptors, protein phosphatase-1, protein phosphatase 2C, protein phosphatase 2B and/or protein phosphatase 2A, for use in such treatments. The invention also provides methods of modulating phosphorylation-dependent activation of AMPA receptors for use in such treatments.

The present invention relates to inhibitors of cyclin-dependent kinases and therapeutic applications thereof. Furthermore, the invention relates to methods of preventing and/or treating any type of pain, inflammatory disorders, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases and neurodegenerative diseases comprising the administration of an effective amount of at least one inhibitor of cyclin-dependent kinases.

Novel pyrazolopyrimidines of formula (I):

are discussed. These pyrazolopyrimidines are capable of inhibiting the activity of cyclin-dependent kinases, most particularly cyclin-dependent kinase 1 (Cdk1), cyclin-dependent kinase 2 (Cdk2), and cyclin-dependent kinase 4 (Cdk4) and are thus useful, inter alia, in the treatment or control of cancer, in particular solid tumors. This invention also provides pharmaceutical compositions containing such compounds and to methods of treating or controlling cancer, most particularly the treatment or control of breast, lung, colon and prostate tumors.

A CDK profile including a ratio of specific activities of two cyclin dependent kinases closely correlates with the malignancy grade and the presence/absence of the sensitivity to an irritant such as an anticancer agent of a cancer tissue in clinical medicine. Therefore, the properties of a mammalian cell, such as malignancy grade, proliferation potency, sensitivity to an irritant such as an anticancer agent can be assessed based on its CDK profile or by comparing the result of a specific activity ratio of two CDKs with a predetermined threshold corresponding to the ratio. This sensitivity assessing method shows a high ratio of correct assessing results particularly in positive or sensitivity and is useful in predicting efficacy of chemotherapy using the anticancer agent.

Compounds having the following structure (I):

or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein one of R¹, R² or R³ is —P(═O)(OH)₂, and the other two of R¹, R² and R³ are each H, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating diseases associated with overexpression of a cyclin-dependent kinase (CDK) are also provided.

The invention relates to a novel synthesis method of a CDK4 (cyclin-dependent kinase 4) inhibitor. A reaction of 2-chloro-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one with acetylchloride is taken as an initial reaction, consequent reactions are performed, and the CDK4 inhibitor is prepared; the preparation method is simple and easy to implement, the yield is high, the quality is high, and industrial production is facilitated.

Compounds of general Formula (I):

wherein R¹, R², R³, R^a, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.

are useful as inhibitors of cyclin dependent kinases such as CDK9.

This invention is directed to aminothiazole compounds of formula (I) wherein R<1> is a substituted or unsubstituted group selected from: C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R<1> is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; and R<2 >is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent to the point of attachment, which ring structure is optionally further substituted, where each substituent of R<2> independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; or a pharmaceutically acceptable salt of a compound of formula (I), or a prodrug or pharmaceutically active metabolite of a compound of formula (I) or pharmaceutically acceptable salt thereof, for inhibiting cyclin-dependent kinases (CDKs), such as CDK1, CDK2, CDK4, and CDK6.

A combination of a CDK4/8 inhibitor and an mTOR inhibitor for the treatment of cancer.