Recommanded Product: 3939-12-6. The protonation of heteroatoms in aromatic heterocycles can be divided into two categories: lone pairs of electrons are in the aromatic ring conjugated system; and lone pairs of electrons do not participate. Compound: 6-Fluoronicotinonitrile, is researched, Molecular C6H3FN2, CAS is 3939-12-6, about Discovery of isoquinolinone and naphthyridinone-based inhibitors of poly(ADP-ribose) polymerase-1 (PARP1) as anticancer agents: Structure activity relationship and preclinical characterization. Author is Karche, Navnath P.; Bhonde, Mandar; Sinha, Neelima; Jana, Gourhari; Kukreja, Gagan; Kurhade, Sanjay P.; Jagdale, Arun R.; Tilekar, Ajay R.; Hajare, Anil K.; Jadhav, Ganesh R.; Gupta, Nishant R.; Limaye, Rohan; Khedkar, Nilesh; Thube, Baban R.; Shaikh, Javed S.; Rao Irlapati, Nageswara; Phukan, Samiron; Gole, Gopal; Bommakanti, Apparao; Khanwalkar, Harshal; Pawar, Yogesh; Kale, Ramesh; Kumar, Rakesh; Gupta, Rajesh; Praveen Kumar, V. R.; Wahid, Saif; Francis, Albi; Bhat, Tariq; Kamble, Nivrutti; Patil, Vinod; Nigade, Prashant B.; Modi, Dipak; Pawar, Shashikant; Naidu, Sneha; Volam, Harish; Pagdala, Vamsi; Mallurwar, Sadanand; Goyal, Hemant; Bora, Pushpak; Ahirrao, Prajakta; Singh, Minakshi; Kamalakannan, Prabhakaran; Naik, Kumar Ram; Kumar, Pradipta; Powar, Rajendra G.; Shankar, Rajesh B.; Bernstein, Peter R.; Gundu, Jayasagar; Nemmani, Kumar; Narasimham, Lakshmi; George, Kochumalayil Shaji; Sharma, Sharad; Bakhle, Dhananjay; Kamboj, Rajender Kumar; Palle, Venkata P..
The exploitation of GLU988 and LYS903 residues in PARP1 as targets to design isoquinolinone and naphthyridinone analogs is described. Compounds of structure I have good biochem. and cellular potency but suffered from inferior PK. Constraining the linear propylene linker of structure into a cyclopentene ring offered improved PK parameters, while maintaining potency for PARP1. Finally, to avoid potential issues that may arise from the presence of an anilinic moiety, the nitrogen substituent on the isoquinolinone ring was incorporated as part of the bicyclic ring. This afforded a naphthyridinone scaffold, as shown in structure naphthyridinones. Further optimization of naphthyridinone series led to identification of a novel and highly potent PARP1 inhibitor I, which was further characterized as preclin. candidate mol. Compound I is orally bioavailable and displayed favorable pharmacokinetic (PK) properties. Compound I demonstrated remarkable antitumor efficacy both as a single-agent as well as in combination with chemotherapeutic agents in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. Addnl., compound I also potentiated the effect of agents such as temozolomide in breast cancer, pancreatic cancer and Ewing’s sarcoma models.
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Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem