191327-95-4Relevant academic research and scientific papers
SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS
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Paragraph 001490; 001492, (2018/04/27)
Provided herein are compounds of the Formula I: (I) or pharmaceutically acceptable salt or solvate thereof, wherein A, B, X1, X2, X3, X4, Ring D, E, Ra, Rb, n and m have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.
THERAPEUTIC COMPOUNDS AND COMPOSITIONS
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Paragraph 0383, (2014/09/30)
Compounds of general formula I: and compositions comprising compounds of general formula I that modulate pyruvate kinase are described herein. Also described herein are methods of using the compounds that modulate pyruvate kinase in the treatment of diseases.
Substituted piperidine derivatives as selective agonists of 5-HT receptors
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, (2008/06/13)
PCT No. PCT/GB96/02765 Sec. 371 Date May 13, 1998 Sec. 102(e) Date May 13, 1998 PCT Filed Nov. 13, 1996 PCT Pub. No. WO97/18202 PCT Pub. Date May 22, 1997A compound of formula (I), or a salt or prodrug thereof, is described, wherein G is attached at posit
Fluorination of 3-(3-(piperidin-1-yl)propyl)indoles and 3-(3-(piperazin- 1-yl)propyl)indoles gives selective human 5-HT(1D) receptor ligands with improved pharmacokinetic profiles
Van Niel, Monique B.,Collins, Ian,Beer, Margaret S.,Broughton, Howard B.,Cheng, Susan K. F.,Goodacre, Simon C.,Heald, Anne,Locker, Karen L.,MacLeod, Angus M.,Morrison, Denise,Moyes, Christopher R.,O'Connor, Desmond,Pike, Andrew,Rowley, Michael,Russell, Michael G. N.,Sohal, Baibinder,Stanton, Josephine A.,Thomas, Steven,Verrier, Hugh,Watt, Alan P.,Castro, José L.
, p. 2087 - 2104 (2007/10/03)
It has previously been reported that a 3-(3-(piperazin-1- yl)propyl)indole series of 5-HT(1D) receptor ligands have pharmacokinetic advantages over the corresponding 3-(3-(piperidin-1-yl)propyl)indole series and that the reduced pK(a) of the piperazines compared to the piperidines may be one possible explanation for these differences. To investigate this proposal we have developed versatile synthetic strategies for the incorporation of fluorine into these ligands, producing novel series of 4- fluoropiperidines, 3-fluoro-4-aminopiperidines, and both piperazine and piperidine derivatives with one or two fluorines in the propyl linker. Ligands were identified which maintained high affinity and selectivity for the 5-HT(1D) receptor and showed agonist efficacy in vitro. The incorporation of fluorine was found to significantly reduce the pK(a) of the compounds, and this reduction of basicity was shown to have a dramatic, beneficial influence on oral absorption, although the effect on oral bioavailability could not always be accurately predicted.
