341998-55-8Relevant articles and documents
ROCK inhibitors 4: Structure-activity relationship studies of 7-azaindole-based rho kinase (ROCK) inhibitors
Bandarage, Upul K.,Court, John,Gao, Huai,Nanthakumar, Suganthini,Come, Jon H.,Giroux, Simon,Green, Jeremy
, (2021/01/04)
Rho kinase (ROCK) inhibitors are of therapeutic value for the treatment of disorders such as hypertension and glaucoma, and potentially of wider use against diseases such as cancer and multiple sclerosis. We previously reported a series of potent and selective ROCK inhibitors based on a substituted 7-azaindole scaffold. Here we extend the SAR exploration of the 7-azaindole series to identify leads for further evaluation. New compounds such as 16, 17, 19, 21 and 22 showed excellent ROCK potency and protein kinase A (PKA) selectivity, combined with microsome and hepatocyte stability.
Design of Novel 3-Pyrimidinylazaindole CDK2/9 Inhibitors with Potent in Vitro and in Vivo Antitumor Efficacy in a Triple-Negative Breast Cancer Model
Singh, Umed,Chashoo, Gousia,Khan, Sameer U.,Mahajan, Priya,Nargotra, Amit,Mahajan, Girish,Singh, Amarinder,Sharma, Anjna,Mintoo, Mubashir J.,Guru, Santosh Kumar,Aruri, Hariprasad,Thatikonda, Thanusha,Sahu, Promod,Chibber, Pankaj,Kumar, Vikas,Mir, Sameer A.,Bharate, Sonali S.,Madishetti, Sreedhar,Nandi, Utpal,Singh, Gurdarshan,Mondhe, Dilip Manikrao,Bhushan, Shashi,Malik, Fayaz,Mignani, Serge,Vishwakarma, Ram A.,Singh, Parvinder Pal
, p. 9470 - 9489 (2017/12/26)
In the present study, a novel series of 3-pyrimidinylazaindoles were designed and synthesized using a bioinformatics strategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription. The present approach gives new dimensions to the existing SAR and opens a new opportunity for the lead optimizations from comparatively inexpensive starting materials. The study led to the identification of the alternative lead candidate 4ab with a nanomolar potency against CDK2 and CDK9 and potent antiproliferative activities against a panel of tested tumor cell lines along with a better safety ratio of ～33 in comparison to reported leads. In addition, the identified lead 4ab demonstrated a good solubility and an acceptable in vivo PK profile. The identified lead 4ab showed an in vivo efficacy in mouse triple-negative breast cancer (TNBC) syngeneic models with a TGI (tumor growth inhibition) of 90% without any mortality growth inhibition in comparison to reported leads.
Concise syntheses of meridianins and meriolins using a catalytic domino amino-palladation reaction
Walker, Scott R.,Czyz, Milena L.,Morris, Jonathan C.
supporting information, p. 708 - 711 (2014/03/21)
A synthesis of natural and synthetic members of the meridianin family of kinase inhibitory natural products has been developed. The sequence utilizes a variation of the Cacchi palladium-catalyzed domino reaction to efficiently construct the heterocyclic f
