64306-77-0Relevant academic research and scientific papers
Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity
Sundriyal, Sandeep,Chen, Patty B.,Lubin, Alexandra S.,Lueg, Gregor A.,Li, Fengling,White, Andrew J. P.,Malmquist, Nicholas A.,Vedadi, Masoud,Scherf, Artur,Fuchter, Matthew J.
supporting information, p. 1069 - 1092 (2017/07/12)
Plasmodium falciparum HKMTs (PfHKMTs) play a key role in controlling Plasmodium gene expression and represent exciting new anti-malarial epigenetic targets. Using an inhibitor series derived from the diaminoquinazoline HKMT inhibitory chemotype, we have previously identified compounds with highly promising antimalarial activity, including irreversible asexual cycle blood stage-independent cytotoxic activity at nM concentrations, oral efficacy in in vivo models of disease, and the unprecedented ability to reactivate dormant liver stage parasites (hypnozoites). However, future development of this series will need to address host versus parasite selectivity, where inhibitory activity against human G9a is removed from the lead compounds, while maintaining potent anti-Plasmodium activity. Herein, we report an extensive study of the SAR of this series against both G9a and P. falciparum. We have identified key SAR features which demonstrate that high parasite vs. G9a selectivity can be achieved by selecting appropriate substituents at position 2, 4 and 7 of the quinazoline ring. We have also, in turn, discovered that potent G9a inhibitors can be identified by employing a 6-carbon 'Nle mimic' at position 7. Together, this data suggests that while broadly similar, the G9a and potential PfHKMT target(s) binding pockets and/or binding modes of the diaminoquinazoline analogues exhibit clear and exploitable differences. Based on this, we believe this scaffold to have clear potential for development into a novel anti-malarial therapeutic.
2-PHENYL-3H-IMIDAZO[4,5-B]PYRIDINE DERIVATES USEFUL AS INHIBITORS OF MAMMALIAN TYROSINE KINASE ROR1 ACTIVITY
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Page/Page column 96-97, (2016/09/22)
A compound of formula (I′) or (I′′) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of mammalian kinase enzyme activity, including ROR1 tyrosine kinase activity and may be used in the treatment of disorders associated with such activity.
SUBSTITUTED BENZIMIDAZOLES AS NOCICEPTIN RECEPTOR MODULATORS
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Page/Page column 94, (2014/10/04)
The invention provides modulators of the nociceptin receptor (NOP), including both agonists and antagonists. A compound of the invention can be a selective modulator of NOP with respect to the μ- and κ- opioid receptors (MOP and KOP), thus providing a therapeutic method for the treatment of conditions wherein selective NOP modulation is medically indicated and MOP or KOP modulation may be less desirable. A compound of the invention can be a NOP full agonist, partial agonist, inverse agonist, positive or negative allosteric modulator, or a functionally biased agonist. A compound of the invention can be used for the treatment of an anxiety state, post-traumatic stress disorder, addictive disorders (including overuse of alcohol, tobacco, and drugs of abuse such as cocaine, amphetamines, and opitates), misregulated food intake and/or energy expenditure, cough, sleep disorders, migraine, pain, depression, or neurodegenerative disorders such as Parkinsons disease or Alzheimers disease.
PYRROLIDINE-3-YLACETIC ACID DERIVATIVE
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Paragraph 0187; 0230, (2014/08/06)
A compound represented by formula (1) or a pharmaceutically acceptable salt thereof has an inhibitory effect in the fractalkine-CX3CR1 pathway: wherein R represents a C1-6 alkyl group unsubstituted or having 1 to 3 substituents selected from Substituent Group A, a C3-8 cycloalkyl group unsubstituted or having 1 to 3 substituents selected from Substituent Group A, or a C3-8 cycloalkenyl group unsubstituted or having 1 to 3 substituents selected from Substituent Group A, X represents a C1-6 alkyl group, Y and Z are the same or different from each other and each represents a halogen atom or a C1-6 alkyl group unsubstituted or having 1 to 3 substituents selected from Substituent Group B, n represents 0 or 1, Substituent Group A consists of halogen atoms, and Substituent Group B consists of halogen atoms.
The design and synthesis of purine inhibitors of CDK2. III
Shum,Peet,Weintraub,Le,Zhao,Barbone,Cashman,Tsay,Dwyer,Loos,Powers,Kropp,Wright,Bitonti,Dumont,Borcherding
, p. 1067 - 1078 (2007/10/03)
Cyclin-dependent kinases (CDKs) belong to a class of enzymes that control the ability of a cell to enter into and proceed through the cell division cycle. Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects.
Anti-psychotic (cycloalkenylalkylpiperidino) benzamides
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, (2008/06/13)
This invention relates to piperidine derivatives. More particularly, the invention relates to substituted benzoic acid amides of N-substituted piperidine and to pharmaceutical compositions thereof, which are useful in antagonizing the effects of dopamine
