858629-06-8Relevant articles and documents
Identification of potent ITK inhibitors through focused compound library design including structural information
Herdemann, Matthias,Heit, Isabelle,Bosch, Frank-Uwe,Quintini, Gianluca,Scheipers, Claudia,Weber, Alexander
, p. 6998 - 7003 (2010)
A series of novel compound libraries inhibiting interleukin-2 inducible T cell kinase (ITK) were designed, synthesized and evaluated. In the first design cycle two library scaffolds were identified showing low micromolar inhibition of ITK. Further iterative design cycles including crystal structure information of ITK and structurally related kinases led to the identification of indolylindazole and indolylpyrazolopyridine compounds with low nanomolar ITK inhibition.
FLUORINE-SUBSTITUTED INDAZOLE COMPOUNDS AND USES THEREOF
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Paragraph 00437, (2018/11/10)
Fluorine-substituted indazole compounds, pharmaceutical compositions containing these compounds and uses thereof. The compounds and pharmaceutical compositions can be used as soluble guanylate cyclase simulators.
4-Aminoquinolone piperidine amides: Noncovalent inhibitors of DprE1 with long residence time and potent antimycobacterial activity
Naik, Maruti,Humnabadkar, Vaishali,Tantry, Subramanyam J.,Panda, Manoranjan,Narayan, Ashwini,Guptha, Supreeth,Panduga, Vijender,Manjrekar, Praveena,Jena, Lalit Kumar,Koushik, Krishna,Shanbhag, Gajanan,Jatheendranath, Sandesh,Manjunatha,Gorai, Gopinath,Bathula, Chandramohan,Rudrapatna, Suresh,Achar, Vijayashree,Sharma, Sreevalli,Ambady, Anisha,Hegde, Naina,Mahadevaswamy, Jyothi,Kaur, Parvinder,Sambandamurthy, Vasan K.,Awasthy, Disha,Narayan, Chandan,Ravishankar, Sudha,Madhavapeddi, Prashanti,Reddy, Jitendar,Prabhakar,Saralaya, Ramanatha,Chatterji, Monalisa,Whiteaker, James,McLaughlin, Bob,Chiarelli, Laurent R.,Riccardi, Giovanna,Pasca, Maria Rosalia,Binda, Claudia,Neres, Jo?o,Dhar, Neeraj,Signorino-Gelo, Fran?ois,McKinney, John D.,Ramachandran, Vasanthi,Shandil, Radha,Tommasi, Ruben,Iyer, Pravin S.,Narayanan, Shridhar,Hosagrahara, Vinayak,Kavanagh, Stefan,Dinesh, Neela,Ghorpade, Sandeep R.
supporting information, p. 5419 - 5434 (2014/07/08)
4-Aminoquinolone piperidine amides (AQs) were identified as a novel scaffold starting from a whole cell screen, with potent cidality on Mycobacterium tuberculosis (Mtb). Evaluation of the minimum inhibitory concentrations, followed by whole genome sequencing of mutants raised against AQs, identified decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1) as the primary target responsible for the antitubercular activity. Mass spectrometry and enzyme kinetic studies indicated that AQs are noncovalent, reversible inhibitors of DprE1 with slow on rates and long residence times of ～100 min on the enzyme. In general, AQs have excellent leadlike properties and good in vitro secondary pharmacology profile. Although the scaffold started off as a single active compound with moderate potency from the whole cell screen, structure-activity relationship optimization of the scaffold led to compounds with potent DprE1 inhibition (IC50 10 nM) along with potent cellular activity (MIC = 60 nM) against Mtb.
