- NAPHTHYRIDINE DERIVATIVES AS ALPHA V BETA 6 INTEGRIN ANTAGONISTS FOR THE TREATMENT OF E.G. FIBROTIC DISEASES
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A compound of formula (I) or a salt thereof wherein R1 represents a five-membered aromatic heterocycle selected from a N- or a C-linked mono- or di-substituted pyrazole, an N- or a C-linked optionally mono- or di-substituted triazole or an N- or a C-linked optionally mono-or di-substituted imidazole, which five-membered aromatic heterocycle may be substituted by one or two of the groups selected from a hydrogen atom, a methyl group, an ethyl group, a fluorine atom, a hydroxymethyl group, a 2-hydroxypropan-2-yl group, a trifluoromethyl group, a difluoromethyl group or a fluoromethyl group, except that when R1 represents an N-linked mono-or di-substituted pyrazole, R1 does not represent 3,5-Dimethyl-1H- pyrazol-1-yl, 5-Methyl-1H-pyrazol-1-yl, 5-Ethyl-3-methyl-1H-pyrazol-1-yl, 3,5-Diethyl-1H-pyrazol-1- yl, 4-Fluoro-3,5-dimethyl-1H-pyrazol-1-yl, 3-Methyl-1H- pyrazol-1-yl or 1H- pyrazol-1-yl.
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Page/Page column 43
(2016/04/20)
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- Synthesis and determination of absolute configuration of a non-peptidic αvβ6 integrin antagonist for the treatment of idiopathic pulmonary fibrosis
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A diastereoselective synthesis of (S)-3-(3-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid (1), a potential therapeutic agent for the treatment of Idiopathic Pulmonary Fibrosis, which is currently undergoing Phase I clinical trials is reported. The key steps in the synthesis involved alkylation of 2-methylnaphthyridine with (R)-N-Boc-3-(iodomethyl)-pyrrolidine, and an asymmetric Rh-catalysed addition of an arylboronic acid to a 4-(N-pyrrolidinyl)crotonate ester. The overall yield of the seven linear step synthesis was 8% and the product was obtained in >99.5% ee proceeding with 80% de. The absolute configuration of 1 was established by an alternative asymmetric synthesis involving alkylation of an arylacetic acid using Evans oxazolidinone chemistry, acylation using the resulting 2-arylsuccinic acid, and reduction. The absolute configuration of the benzylic asymmetric centre was established as (S).
- Anderson, Niall A.,Campbell, Ian B.,Fallon, Brendan J.,Lynn, Sean M.,Macdonald, Simon J. F.,Pritchard, John M.,Procopiou, Panayiotis A.,Sollis, Steven L.,Thorp, Lee R.
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p. 5992 - 6009
(2016/07/06)
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- NAPHTHYRIDINE DERIVATIVES USEFUL AS ALPHA-V-BETA-6 INTEGRIN ANTAGONISTS
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A compound of formula (I) or a salt thereof (I) wherein R1 represents a hydrogen atom, a methyl group or a ethyl group R2 represents a hydrogen atom or a fluorine atom R3 represents a hydrogen atom, a methyl group or an ethyl group.
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Page/Page column 32
(2014/10/15)
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- Enantioselective construction of all-carbon quaternary stereocenters using palladium-catalyzed asymmetric allylic alkylation of γ-acetoxy-α, β-unsaturated carbonyl compounds
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We have successfully demonstrated that γ-acetoxy-α,β- unsaturated carbonyl compounds are useful starting materials for Pd-catalyzed asymmetric allylic alkylation to construct all-carbon quaternary stereocenters. With the use of 2-5 mol % of Pd catalyst an
- Nemoto, Tetsuhiro,Fukuda, Tomoaki,Matsumoto, Takayoshi,Hitomi, Tsukasa,Hamada, Yasumasa
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p. 1504 - 1506
(2007/10/03)
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