8-THP-DHI analogs as potent Type I dual TIE-2/VEGF-R2 receptor tyrosine kinase inhibitors.

A novel series of 8-(2-tetrahydropyranyl)-12,13-dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazoles (THP-DHI) was synthesized and evaluated as dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors. Development of the structure-activity relationships (SAR) with the support of X-ray crystallography led to identification of 7f and 7g as potent, selective dual TIE-2/VEGF-R2 inhibitors with excellent cellular potency and acceptable pharmacokinetic properties. Compounds 7f and 7g were orally active in tumor models with no observed toxicity.

Hudkins RL ，Zulli AL ，Underiner TL ，Angeles TS ，Aimone LD ，Meyer SL ，Pauletti D ，Chang H ，Fedorov EV ，Almo SC ，Fedorov AA ，Ruggeri BA ... -  《-》

Design and synthesis of dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole oximes as potent dual inhibitors of TIE-2 and VEGF-R2 receptor tyrosine kinases.

Dandu R ，Zulli AL ，Bacon ER ，Underiner T ，Robinson C ，Chang H ，Miknyoczki S ，Grobelny J ，Ruggeri BA ，Yang S ，Albom MS ，Angeles TS ，Aimone LD ，Hudkins RL ... -  《-》

Novel C-3 N-urea, amide, and carbamate dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs as potent TIE-2 and VEGF-R2 dual inhibitors.

Becknell NC ，Zulli AL ，Angeles TS ，Yang S ，Albom MS ，Aimone LD ，Robinson C ，Chang H ，Hudkins RL ... -  《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》

TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs.

Underiner TL ，Ruggeri B ，Aimone L ，Albom M ，Angeles T ，Chang H ，Hudkins RL ，Hunter K ，Josef K ，Robinson C ，Weinberg L ，Yang S ，Zulli A ... -  《-》

A new class of potent vascular endothelial growth factor receptor tyrosine kinase inhibitors: structure-activity relationships for a series of 9-alkoxymethyl-12-(3-hydroxypropyl)indeno[2,1-a]pyrrolo[3,4-c]carbazole-5-ones and the identification of CEP-521

Gingrich DE ，Reddy DR ，Iqbal MA ，Singh J ，Aimone LD ，Angeles TS ，Albom M ，Yang S ，Ator MA ，Meyer SL ，Robinson C ，Ruggeri BA ，Dionne CA ，Vaught JL ，Mallamo JP ，Hudkins RL ... -  《JOURNAL OF MEDICINAL CHEMISTRY》