HRP20190668T1 - Tetrazolonom supstituirani dihidropiridinonski mgat2 inhibitori - Google Patents

Tetrazolonom supstituirani dihidropiridinonski mgat2 inhibitori Download PDF

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HRP20190668T1
HRP20190668T1 HRP20190668TT HRP20190668T HRP20190668T1 HR P20190668 T1 HRP20190668 T1 HR P20190668T1 HR P20190668T T HRP20190668T T HR P20190668TT HR P20190668 T HRP20190668 T HR P20190668T HR P20190668 T1 HRP20190668 T1 HR P20190668T1
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alkyl
independently selected
haloalkyl
phenyl
compound
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Saleem Ahmad
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Bristol-Myers Squibb Company
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Claims (16)

1. Spoj sa Formulom (I): ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, polimorf, solvat ili hidrat tog spoja, gdje: prsten A je nezavisno 5- do 6-očlani heteroaril koji sadrži ugljikove atome i 1-4 heteroatoma odabrana od N, NRe, O i S; gdje spomenuti heteroaril je supstituiran sa 0-1 R6 i 0-2 R7; R1 je nezavisno odabrano od: -(CH2)m-(C3-6 karbociklus supstituiran sa 0-2 Rb i 0-2 Rg), -(CH2)m-(5- do 6-očlani heteroaril koji sadrži ugljikove atome i 1-4 heteroatoma odabrana od N, NRe, O i S; gdje spomenuti heteroaril je supstituiran sa 0-1 Rb i 0-2 Rg), i (C1-12 ugljikovodični lanac supstituiran sa 0-3 Ra; gdje spomenuti ugljikovodični lanac može biti ravan ili razgranat, zasićen ili nezasićen); R2 je nezavisno odabrano od: C1-4 alkil, C3-4 cikloalkil, i C1-4 haloalkil; R3 je nezavisno odabrano od: H, F, C1-4 alkil i CN; R4 je nezavisno odabrano od: H, F, i C1-4 alkil; R3 i R4 mogu biti kombinirani sa ugljikovim atomom za koji su oni vezani da formiraju 3- do 6-očlani karbociklus; R6 je nezavisno odabrano od: halogen, C1-6 alkil supstituiran sa 0-2 Rh, C1-4 alkoksi, C1-4 haloalkil, C1-4 haloalkoksi, CO(C1-4 alkil), -(CH2)m-C3-6 karbociklus, -(CH2)m-NRfRi, CN, ORi, SRi, i (4- do 6-očlani heterociklus koji sadrži ugljikove atome i 1-4 heteroatoma odabrana od N, NRe, O, i S); R7 je nezavisno odabrano od: halogen, C1-4 alkil, C1-4 alkoksi, C1-4 haloalkil, i C1-4 haloalkoksi; alternativno, R6 i R7, zajedno sa ugljikovim atomima za koje su oni vezani, se kombiniraju da formiraju 5- do 6-očlani karbociklični prsten ili 5- do 6-očlani heterociklični prsten koji sadrži ugljikove atome i 1-3 heteroatoma odabrana od N, NRe, O, i S; gdje spomenuti heterociklus je supstituiran sa 0-2 Rg; Ra je, pri svakom pojavljivanju, nezavisno odabrano od: halogen, OH, C1-6 alkoksi, C1-6 haloalkil, C1-6 haloalkoksi, N(C1-4 alkil)2, COOH, i -(CH2)n-Rc; Rb je, pri svakom pojavljivanju, nezavisno odabrano od: halogen, OH, C1-10 alkil, C1-10 alkoksi, C1-10 haloalkil, C1-10 haloalkoksi, C1-10 alkiltio, C1-10 haloalkiltio, N(C1-4 alkil)2, -CONH(C4-20 alkil), -CONH(C4-20 haloalkil), -O(CH2)sO(C1-6 alkil), -O(CH2)sO(C1-6 haloalkil), Rc, i -(CH2)n-(O)t-(CH2)mRc; Rc je, pri svakom pojavljivanju, nezavisno odabrano od: C3-6 cikloalkil supstituiran sa 0-2 Rd, C3-6 cikloalkenil supstituiran sa 0-2 Rd, -(CH2)m-(fenil supstituiran sa 0-3 Rd), i (5- do 6-očlani heterociklus koji sadrži ugljikove atome i 1-4 heteroatoma odabrana od N, NRe, O, i S; gdje spomenuti heterociklus je supstituiran sa 0-2 Rd); Rd je, pri svakom pojavljivanju, nezavisno odabrano od: halogen, OH, CN, NO2, C1-4 alkil, C1-4 alkoksi, C1-4 haloalkil, C1-4 haloalkoksi, tetrazolil, OBn i fenil; Re je, pri svakom pojavljivanju, nezavisno odabrano od: H, C1-8 alkil, C1-8 haloalkil, -(CH2)n-C3-6 karbociklus, CO(C1-4 alkil) i COBn; Rf je, pri svakom pojavljivanju, nezavisno odabrano od: H i C1-4 alkil; Rg je, pri svakom pojavljivanju, nezavisno odabrano od: halogen, C1-4 alkil, C1-4 alkoksi, C1-4 haloalkil, i C1-4 haloalkoksi; Rh je, pri svakom pojavljivanju, nezavisno odabrano od: OH, halogen, C1-4 alkil, C1-4 alkoksi, C1-4 haloalkil, i C1-4 haloalkoksi; Ri je, pri svakom pojavljivanju, nezavisno odabrano od grupe koja se sastoji od C1-4 alkil, C3-4 cikloalkil i fenil; n, pri svakom pojavljivanju, je nezavisno 0 ili 1; m, pri svakom pojavljivanju, je nezavisno 0, 1, 2, 3, ili 4; s, pri svakom pojavljivanju, je nezavisno 1, 2, ili 3; i t, pri svakom pojavljivanju, je nezavisno 0 ili 1.
2. Spoj u skladu sa patentnim zahtjevom 1, gdje: R1 je nezavisno odabrano od: (C3-6 karbociklus supstituiran sa 0-2 Rb i 0-2 Rg), i (5- do 6-očlani heteroaril koji sadrži ugljikove atome i 1-4 heteroatoma odabrana od N, NRe, O i S; gdje spomenuti heteroaril je supstituiran sa 0-1 Rb i 0-2 Rg); R3 je nezavisno odabrano od: H, F, C1-4 alkil i CN; R4 je nezavisno odabrano od: H, F, i C1-4 alkil; Rb je, pri svakom pojavljivanju, nezavisno odabrano od: halogen, C1-10 alkil, C1-10 alkoksi, C1-10 haloalkil, C1-10 haloalkoksi, C1-10 alkiltio, C1-10 haloalkiltio, N(C1-4 alkil)2, -CONH(C4-20 alkil), -CONH(C4-20 haloalkil), -O(CH2)sO(C1-6 alkil), -O(CH2)sO(C1-6 haloalkil), Rc, i -(CH2)n-(O)t-(CH2)mRc; i Rd je, pri svakom pojavljivanju, nezavisno odabrano od: halogen, C1-4 alkil, C1-4 alkoksi, C1-4 haloalkil, C1-4 haloalkoksi, tetrazolil, OBn i fenil.
3. Spoj u skladu sa patentnim zahtjevom 1, gdje: prsten A je nezavisno odabran od pirolil, tienil, tiazolil, pirazolil, piridil, i pirimidinil; gdje svaki segment prstena je supstituiran sa 0-1 R6 i 0-2 R7; i alternativno, R6 i R7, zajedno sa ugljikovim atomima za koje su oni vezani, se kombiniraju da formiraju 6-očlani karbociklični prsten.
4. Spoj u skladu sa patentnim zahtjevom 1, gdje: prsten A je nezavisno odabran od:
R1 je nezavisno odabrano od: (fenil supstituiran sa 1 Rb i 0-2 Rg), i (5-očlani heteroaril koji sadrži ugljikove atome i 1-2 heteroatoma odabrana od N, NRe, O i S; gdje spomenuti heteroaril je supstituiran sa 0-1 Rb i 0-2 Rg); R2 je nezavisno odabrano od: C1-4 alkil i C1-4 haloalkil; R6 je nezavisno odabrano od: halogen, C1-6 alkil sa 0-1 OH, C1-4 alkoksi, C1-4 haloalkoksi, CO(C1-4 alkil), N(C1-4 alkil)2, i -(CH2)0-1-C3-6 cikloalkil; R7 je nezavisno odabrano od: halogen, C1-4 alkil i C1-4 alkoksi; alternativno, R6 i R7, zajedno sa ugljikovim atomima za koje su oni vezani, se kombiniraju da formiraju 6-očlani karbociklični prsten; Rb je, pri svakom pojavljivanju, nezavisno odabrano od: halogen, C1-8 alkil, C1-8 alkoksi, C1-8 haloalkil, C1-10 haloalkoksi, i fenoksi; Re je, pri svakom pojavljivanju, nezavisno odabrano od: C1-6 alkil, C1-8 haloalkil, i -(CH2)n-C3-6 karbociklus; i Rg je, pri svakom pojavljivanju, nezavisno odabrano od: halogen, C1-4 alkil, C1-4 alkoksi, C1-4 haloalkil, i C1-4 haloalkoksi.
5. Spoj sa Formulom (IIb), (IId), ili (IIe) u skladu sa bilo kojim od patentnih zahtjeva 1-4:
ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, polimorf, solvat ili hidrat tog spoja, gdje: R1 je nezavisno odabrano od: R2 je nezavisno odabrano od: CF3 i CH3; R6 je nezavisno odabrano od: halogen, C1-4 alkil supstituiran sa 0-1 OH, C1-4 alkoksi, C1-4 haloalkoksi, CO(C1-4 alkil), i -(CH2)0-1-C3-4 cikloalkil; Rb je nezavisno odabrano od: -(CH2)1-6CF3, -(CH2)1-4CF2CF3, -O(CH2)1-6CF3, i -O(CH2)1-4CF2CF3; Re je, pri svakom pojavljivanju, nezavisno odabrano od: C1-4 alkil, -(CH2)1-6CF3, i -(CH2)0-1-C3-4 cikloalkil; i Rg je nezavisno halogen.
6. Spoj u skladu sa patentnim zahtjevom 5, gdje: R1 je
7. Spoj u skladu sa patentnim zahtjevima 1-6, gdje spoj je odabran od (S)-6-(2-fluoro-4-(4,4,4-trifluorobutoksi)fenil)-4-(1-izopropil-1H-pirazol-3-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(1-ciklopropil-1H-pirazol-3-il)-6-(2-fluoro-4-(4,4,4-trifluorobutoksi)fenil)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(1-ciklobutil-1H-pirazol-3-il)-6-(2-fluoro-4-(4,4,4-trifluorobutoksi)fenil)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(1-etil-1H-pirazol-3-il)-6-(2-fluoro-4-(4,4,4-trifluorobutoksi)fenil)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-6-(2-fluoro-4-(5,5,5-trifluoropentil)fenil)-4-(1-izopropil-1H-pirazol-3-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(1-(ciklopropilmetil)-1H-pirazol-3-il)-6-(2-fluoro-4-(5,5,5-trifluoropentil) fenil)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-6-(2-fluoro-4-(5,5,5-trifluoropentil)fenil)-4-(1-izobutil-1H-pirazol-3-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(1-etil-1H-pirazol-3-il)-6-(2-fluoro-4-(5,5,5-trifluoropentil)fenil)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(1-(ciklopropilmetil)-1H-pirazol-3-il)-6-(2-fluoro-4-(4,4,4-trifluorobutoksi) fenil)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-6-(2-fluoro-4-(4,4,4-trifluorobutoksi)fenil)-4-(1-izobutil-1H-pirazol-3-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(1-(ciklobutilmetil)-1H-pirazol-3-il)-6-(2-fluoro-4-(4,4,4-trifluorobutoksi) fenil)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(5-acetiltiofen-2-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(4-(4,4,4-trifluorobutoksi)fenil)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (6S)-4-(5-(1-hidroksietil)tiofen-2-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(4-(4,4,4-trifluorobutoksi)fenil)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(1-(ciklopropilmetil)-1H-pirazol-3-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-6-(4-(5,5,5-trifluoropentil)fenil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(5-ciklopropiltiazol-2-il)-6-(2-fluoro-4-(4,4,4-trifluorobutoksi)fenil)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-4-(5-etiltiofen-2-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-6-(4-(4,4,4-trifluorobutoksi)fenil)-6-(trifluorometil)-5,6-dihidropiridin-2(1H)-on; (S)-6-(2-hloro-4-(4,4,4-trifluorobutoksi)fenil)-4-(5-etiltiofen-2-il)-3-(5-okso-4,5-dihidro-1H-tetrazol-1-il)-5,6-dihidropiridin-2(1H)-on; ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, polimorf, solvat ili hidrat tog spoja.
8. Spoj iz bilo kojeg prethodnog patentnog zahtjeva, gdje spoj ima sljedeću formulu: ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, polimorf, solvat ili hidrat tog spoja.
9. Spoj iz patentnog zahtjeva 8, gdje spoj je:
10. Farmaceutska kompozicija, koja sadrži farmaceutski prihvatljivi nosač i spoj iz bilo kojeg od patentnih zahtjeva 1-9.
11. Spoj iz bilo kojeg od patentnih zahtjeva 1-9, gdje spoj ima hMGAT2 IC50 vrijednosti ≤ 1 µM, korištenjem MGAT2 LCMS testa.
12. Spoj iz bilo kojeg od patentnih zahtjeva 1-9, gdje spoj ima hMGAT2 IC50 vrijednosti ≤ 0.5 µM, korištenjem MGAT2 LCMS testa.
13. Spoj iz bilo kojeg od patentnih zahtjeva 1-9, gdje spoj ima hMGAT2 IC50 vrijednosti ≤ 0.1 µM, korištenjem MGAT2 LCMS testa.
14. Farmaceutska kompozicija koja sadrži spoj u skladu sa bilo kojim od patentnih zahtjeva 1-9 i koja dalje sadrži inhibitor dipeptidil peptidaze-IV (DPP4).
15. Spoj u skladu sa bilo kojim od patentnih zahtjeva 1-9 za primjenu u terapiji.
16. Spoj u skladu sa bilo kojim od patentnih zahtjeva 1-9 za primjenu u liječenju najmanje jedne bolesti ili poremećaja odabranih iz grupe koja se sastoji od dijabetesa, hiperglikemije, poremećene tolerancije glukoze, gestacionog dijabetesa, inzulinske rezistencije, hiperinzulinemije, bolesti nealkoholne masne jetre (nonalcoholic fatty liver disease - NAFLD) uključujući nealkoholni steatohepatitis (NASH), retinopatije, neuropatije, nefropatije, odgođenog zarastanja rane, ateroskleroze i njenih posljedica, abnormalne srčane funkcije, miokardijalne ishemije, moždanog udara, metaboličkog sindroma, hipertenzije, pretilosti, dislipidemije, dislipidemije, hiperlipidemije, hipertrigliceridemije, hiperholesterolemije, niskog lipoproteina visoke gustoće (high-density lipoprotein - HDL), visokog lipoproteina niske gustoće (low-density lipoprotein - LDL), ne-kardijalne ishemije, lipidnih poremećaja i/ili glaukoma.
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US9974778B2 (en) 2014-06-11 2018-05-22 Bristol-Myers Squibb Company Substituted pyridinones as MGAT2 inhibitors
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EP3395798A4 (en) 2015-12-21 2019-07-17 Shionogi & Co., Ltd NON-AROMATIC HETEROCYCLIC DERIVATIVE HAVING MGAT2 INHIBITORY ACTIVITY
JP2020158390A (ja) * 2017-06-20 2020-10-01 塩野義製薬株式会社 Ｍｇａｔ２阻害活性を有する非芳香族複素環誘導体およびそれらを含有する医薬組成物
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US20220135577A1 (en) 2019-01-11 2022-05-05 Shionogi & Co., Ltd. Dihydropyrazolopyrazinone derivative having mgat2 inhibitory activity
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US20100016365A1 (en) 2008-07-17 2010-01-21 Auspex Pharmaceuticals, Inc. Substituted 4-amino-piperidines
US8791091B2 (en) 2011-12-02 2014-07-29 Bristol-Myers Squibb Company Aryl dihydropyridinone and piperidinone MGAT2 inhibitors
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