The process development of RG 12525 (2-{[4-(Tetrazol-5-ylmethylphenyl)-methoxy]phenoxymethyl}quinoline)
This contribution describes process improvements to provide a practical and cost-effective synthesis for the manufacture of RG 12525 which resulted in a 3-fold increase in overall yield. Improved solvent systems for chlorination and azidation reactions are described. Adjustments to the tetrazole-forming step eliminated azide sublimation and minimised this risk on scale-up. A robust solvent system was found to control the polymorphic form during crystallisation, which had hitherto been difficult due to the near-equivalence of melting points (154 and 157 °C) of the two known forms.
Bridge, Andrew W.,Jones, Ronald H.,Kabir, Humayun,Kee, Alex A.,Lythgoe, David J.,Nakach, Mustafa,Pemberton, Clive,Wrightman, John A.
The use of triaryl acid derivatives of formula (I) and their pharmaceutical compositions as PPAR ligand receptor binders. The PPAR ligand receptor binders of this invention are useful as agonists or antagonists of the PPAR receptor.
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Page/Page column 222-223; 229
(2010/10/20)
Therapeutic uses of quinoline derivatives
A method for mediating the activity of PPAR-γ receptor comprising contacting said PPAR-γ receptor with a compound of formula I defined herein. Also disclosed is the treatment of a patient suffering from a physiological disorder capable of being modulated
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(2008/06/13)
Approaches to p-hydroxyphenoxymethylquinolines which avoid intermediate chloromethylquinolines for the synthesis of the LTD4 antagonist, RG 12525
As part of an effort to develop an industrial synthesis of the LTD4 antagonist RG 12525 (1), several approaches to the intermediate (2-quinolinylmethoxy)phenol 3 were investigated that avoided the generation of the lachrymatory sensitizer α-chloro-2-methylquinoline 2. Utilization of a cyclic sulfate in place of α,α'dichloro-o-xylene 4 showed promise as a selective dialkylating agent in the conversion of 3 to RO 12525 (1).
O'Brien,Sledeski,Truesdale
p. 509 - 512
(2007/10/03)
A convergent synthesis of an LTD4 antagonist, RG12525
An efficient, convergent synthesis of an LTD4 antagonist, RG12525 (1) has been achieved through the alkylation of the (2-quinolinylmethoxy)phenol (2) with either a triphenylmethyl protected tetrazole synthon (4a) or with a tetrahydropyranyl derivative (4b). Preparation of synthons 4a and 4b, as well as novel preparation of 2 is described.
Sledeski, Adam W.,O'Brien, Michael K.,Truesdale, Larry K.
p. 1129 - 1132
(2007/10/03)
Quinoline derivatives and their use as antagonists of leukotriene D4
This invention relates to quinolinyl-diaryl compounds and their use as leukotriene D4 antagonists for the treatment of hypersensitive disorders.
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(2008/06/13)
Development of a Novel Series of (2-quinolinylmethoxy)phenyl-Containing Compounds as High-Affinity Leukotriene D4 Receptor Antagonists. 2. Effects of an Additional Phenyl Ring on Receptor Affinity
This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety.The compounds reported in this paper contain an additional phenyl ring, which
Huang, Fu-Chih,Galemmo, Robert A.,Johnson, William H.,Poli, Gregory B.,Morrissette, Matthew M.,et al.
p. 1194 - 1200
(2007/10/02)
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