DK2621493T3 - N1-PYRAZOLOSPIROKETON-ACETYL-CoA-CARBOXYLASE-INHIBITORER - Google Patents

N1-PYRAZOLOSPIROKETON-ACETYL-CoA-CARBOXYLASE-INHIBITORER Download PDF

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DK2621493T3
DK2621493T3 DK11768163.5T DK11768163T DK2621493T3 DK 2621493 T3 DK2621493 T3 DK 2621493T3 DK 11768163 T DK11768163 T DK 11768163T DK 2621493 T3 DK2621493 T3 DK 2621493T3
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oxo
indazole
tetrahydro
carbonyl
spiro
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Mary Theresa Didiuk
Robert Lee Dow
David Andrew Griffith
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Claims (16)

1. Forbindelse med formel (I)
eller et farmaceutisk acceptabelt salt deraf; hvor R1 er (Ci-C6)alkyl, (C3-C7)cycloalkyl, tetrahydrofuranyl eller oxetanyl; hvor (CrC6)alkylet eventuelt er substitueret med 1 til 3 substituenter uafhængigt udvalgt fra (CrC3)alkoxy, hydroxy, fluor, phenyl, tetrahydrofuranyl eller oxetanyl; R2 er hydrogen, halogen, (CrC3)alkyl eller cyano; R3 hver især uafhængigt er hydrogen eller (CrC3)alkyl; L er en direkte binding eller et (CrC6)alkylet, hvor et carbon af (Cr C6)alkylenet eventuelt er erstattet med -C(O)-, -C(0)NH-, -NHC(O)-, -O-, -S-, NH eller N(CrC3)alkyl; Z er CH2 eller O; A1 og A2 hver især uafhængigt er (C6-Ci0)aryl, 5- til 12-leddet heteroaryl eller 8- til 12-leddet kondenseret heterocyclicaryl; hvor (C6-C-i0)arylet, det 5- til 12-leddede heteroaryl eller 8- til 12-leddede kondenserede heterocyclicaryl hver især eventuelt er substitueret med en til tre substituenter uafhængigt udvalgt fra (CrC3)alkyl, (CrC3)alkoxy, halogen, amino, (CrC3)alkylamino, di(Cr C3)alkylamino, hydroxy, cyano og amido, hvor alkyldelen af (CrC3)alkylet, (CrC3)alkoxyet, (CrC3)alkylaminoet og di(C-i-C3)alkylaminoet eventuelt er substitueret med en til fem fluor; og hvor et af A1 eller A2 er substitueret med C02R4, (CrC6)C02R4, tetrazolyl eller (CrC6)tetrazolyl; og R4 er (Ci-C8)alkyl, (C3-C8)cycloalkyl eller (Ci-C6)alkyl-(C3-C8)cycloalkyl; eller et farmaceutisk acceptabelt salt deraf.
2. Forbindelse ifølge krav 1, hvor R1 er (CrC6)alkyl, (C3-C7)cycloalkyl eller tetrahydrofuranyl; R2 er hydrogen eller methyl; hvert R3 er hydrogen; og L er en direkte binding eller O; eller et farmaceutisk acceptabelt salt deraf.
3. Forbindelse ifølge krav 2, hvor R1 er (C2-C4)alkyl; A1 og A2 hver især uafhængigt er phenyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, pyrimidinyl, in-dolyl, benzopyrazinyl, benzoimidazolyl, benzoimidazolonyl, pyrrolopyridinyl, pyrrolopyrimidinyl, pyrazolopyridinyl, pyrazolopyrimidinyl, indazolyl, indolino-nyl, naphthyridinyl, quinolinyl, quinolinonyl, dihydroquinolinonyl, oxo-dihydroquinolinonyl, isoquinolinyl, isoquinolinonyl, dihydroisoquinonyl eller oxo-dihydroisoquinonyl, hvor hvert A1 og A2 eventuelt er substitueret med en til tre substituenter uafhængigt udvalgt fra fluor, chlor, methyl, methoxy, amino, methylamino, dimethylamino, amido eller cyano; eller et farmaceutisk acceptabelt salt deraf.
4. Forbindelse ifølge krav 3, hvor R1 er isopropyl eller t-butyl; og R2 er hydrogen; eller et farmaceutisk acceptabelt salt deraf.
5. Forbindelse ifølge krav 4, hvor A1 er phenyl, pyridinyl, indazolyl, indolyl, benzoimidazolyl, pyrrolopyridinyl eller pyrrolopyrimidinyl; hver især eventuelt substitueret med et methyl, methoxy, methylamino eller dimethylamino; eller et farmaceutisk acceptabelt salt deraf.
6. Forbindelse ifølge krav 4 eller 5, hvor A2 er phenyl, som er substitueret med C02H eller tetrazolyl; og L er en direkte binding; eller et farmaceutisk acceptabelt salt deraf.
7. Forbindelse ifølge krav 6, hvor A1 er phenyl, indolyl elle benzoimidazolyl eventuelt substitueret med methyl eller pyridinyl eventuelt substitueret med methylamino eller dimethylamino; eller et farmaceutisk acceptabelt salt deraf.
8. Forbindelse, der er udvalgt fra: 4-((4-(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydrospiro[indazol-5,4'-piperidin]-1 '-ylcarbonyl)phenoxy)methyl)benzoesyre; 3-(4-(1 -lsopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazol-5,4'-piperidin]-1 '-ylcarbonyl)-6-methoxypyridin-2-yl)benzoesyre; 3-(4-(1 -isopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazol-5,4'-piperidin]-1 '-ylcarbonyl)-6-oxo-1,6-dihydropyridin-2-yl)benzoesyre; 3-{5-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-(methylamino)pyridin-2-yl}benzoesyre; 3- {5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 ’H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-6-(methylamino)pyridin-2-yl}benzoesyre; 4'-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]biphenyl-3-carboxylsyre; 4'-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]biphenyl-3-carboxylsyre; 4- {5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-6-(methylamino)pyridin-2-yl}benzoesyre; 4-{4-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-6-methoxypyridin-2-yl}benzoesyre; 3- {4-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-6-methoxypyridin-2-yl}benzoesyre; 4- {4-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-6-methoxypyridin-2-yl}benzoesyre; 3- {4-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-6-methoxypyridin-2-yl}benzoesyre; 4- {5-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-6-(methylamino)pyridin-2-yl}benzoesyre; 4-{5-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-6-(ethylamino)pyridin-2-yl}benzoesyre; 4-{6-(ethylamino)-5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1'-yl)carbonyl]pyridin-2-yl}benzoesyre; 3-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-1 H-indol-4-yl}benzoesyre; 4-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1 H-indol-4-yl}benzoesyre; 3- {2-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1 H-indol-4-yl}benzoesyre; 4- {2-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1H-indol-4-yl}benzoesyre; 3-{5-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-(ethylamino)pyridin-2-yl}benzoesyre; 3-{6-(ethylamino)-5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1'-yl)carbonyl]pyridin-2-yl}benzoesyre; 3- [(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-5-(1,3-oxazol-2-yl)benzoesyre; 4- ({4-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1'-yl)carbonyl]phenoxy}methyl)benzoesyre; 3-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-5-(1,3-oxazol-2-yl)benzoesyre; 3- {6-(isopropylamino)-5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 Ή-spiro[indazol-5,4'-piperidin]-1'-yl)carbonyl]pyridin-2-yl}benzoesyre; 4- {5-[(1 -tert-butyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-(isopropylamino)pyridin-2-yl}benzoesyre; 4-{6-(isopropylamino)-5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 Ή-spiro[indazol-5,4'-piperidin]-1'-yl)carbonyl]pyridin-2-yl}benzoesyre; 4-{6-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1 H-indazol-4-yl}benzoesyre; 3- {4-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-oxo-1,6-dihydropyridin-2-yl}benzoesyre; 4- {4-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-oxo-1,6-dihydropyridin-2-yl}benzoesyre; 3- {2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1 H-pyrrolo[2,3-b]pyridin-4-yl}benzoesyre; 4- {2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1 H-pyrrolo[2,3-b]pyridin-4-yl}benzoesyre; 4-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1H-pyrrolo[3,2-c]pyridin-4-yl}benzoesyre; (5-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-1 H-indol-4-yl}-2-methoxyphenyl)eddikesyre; 3- {6-(dimethylamino)-4-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 Ή-spirotindazol-S^'-piperidinl-l'-ylJcarbonyllpyridin^-ylJbenzoesyre; 4- {6-(dimethylamino)-4-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 Ή-spirotindazol-S^'-piperidinl-l'-ylJcarbonyllpyridin^-ylJbenzoesyre; 4-{6-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}benzoesyre; 3-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1 H-pyrrolo[3,2-c]pyridin-4-yl}benzoesyre; 3- {6-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}benzoesyre; 4- {6-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1 H-indol-4-yl}benzoesyre; 4-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1H-pyrrolo[2,3-c]pyridin-4-yl}benzoesyre; 3-{6-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1 H-indol-4-yl}benzoesyre; 3-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1H-pyrrolo[2,3-c]pyridin-4-yl}benzoesyre; 3- {2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1H-indol-6-yl}benzoesyre; 4- {5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-[(2,2,2-trifluorethyl)amino]pyridin-2-yl}benzoesyre; 3- {5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-(methylamino)pyridin-3-yl}benzoesyre; 4- {5-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-(methylamino)pyridin-3-yl}benzoesyre; 3-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1H-benzimidazol-4-yl}benzoesyre; 4-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1H-benzimidazol-5-yl}benzoesyre; 3-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-1H-benzimidazol-5-yl}benzoesyre; 3- (6-(1 -isopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazol-5,4'-piperidin]-1 ylcarbonyl)-2-methyl-1H-benzo[d]imidazol-4-yl)benzoesyre; 4- (6-(1 -isopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazol-5,4'-piperidin]-1 ylcarbonyl)-2-methyl-1H-benzo[d]imidazol-4-yl)benzoesyre; 1 -isopropyl-1 '-{[3'-(1 H-tetrazol-5-yl)biphenyl-4-yl]carbonyl}-1,4-dihydrospiro[indazol-5,4'-piperidin]-7(6H)-on; og 1 -tert-butyl-1 '-{[3'-(1 H-tetrazol-5-yl)biphenyl-4-yl]carbonyl}-1,4-dihydrospiro[indazol-5,4'-piperidin]-7(6H)-on; eller et farmaceutisk acceptabelt salt deraf.
9. Forbindelse ifølge krav 8, som er udvalgt fra 3- {2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-1 H-benzimidazol-4-yl}benzoesyre; 4- {6-(dimethylamino)-4-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 Ή-spiro[indazol-5,4'-piperidin]-1'-yl)carbonyl]pyridin-2-yl}benzoesyre; 3-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-1 H-indol-4-yl}benzoesyre; 3- {2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-1 H-pyrrolo[2,3-b]pyridin-4-yl}benzoesyre; 4- {2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-1H-benzimidazol-5-yl}benzoesyre; 3-{2-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 '-yl)carbonyl]-1 H-benzimidazol-5-yl}benzoesyre; eller et farmaceutisk acceptabelt salt deraf.
10. Forbindelse ifølge krav 8, som er 4-{4-[(1 -isopropyl-7-oxo-1,4,6,7-tetrahydro-1 'H-spiro[indazol-5,4'-piperidin]-1 yl)carbonyl]-6-methoxypyridin-2-yl}benzoesyre; eller et farmaceutisk acceptabelt salt deraf.
11. Farmaceutisk sammensætning, som omfatter en terapeutisk virksom mængde af en forbindelse ifølge et af kravene 1 til 10; eller et farmaceutisk acceptabelt salt deraf og et farmaceutisk acceptabelt hjælpestof, fortyndingsmiddel eller bæremiddel.
12. Sammensætning ifølge krav 11, hvilken sammensætning endvidere omfatter mindst et yderligere antidiabetisk middel.
13. Sammensætning ifølge krav 12, hvor det antidiabetiske middel er udvalgt fra gruppen bestående af metformin, acetohexamid, chlorpropamid, diabine-se, glibenclamid, glipizid, glyburid, glimepirid, gliclazid, glipentid, gliquidon, glisolamid, tolazamid, tolbutamid, tendamistat, trestatin, acarbose, adiposin, camiglibose, emiglitat, miglitol, voglibose, pradimicin-Q, salbostatin, balagli-tazon, ciglitazon, darglitazon, englitazon, isaglitazon, pioglitazon, rosiglitazon, troglitazon, exendin-3, exendin-4, trodusquemin, reservatrol, hyrtiosal-ekstrakt, sitagliptin, vildagliptin, alogliptin og saxagliptin.
14. Forbindelse ifølge et af kravene 1 til 10 eller et farmaceutisk acceptabelt salt deraf eller en farmaceutisk sammensætning ifølge et af kravene 11 til 13 til anvendelse som et medikament.
15. Forbindelse ifølge et af kravene 1 til 10 eller et farmaceutisk acceptabelt salt deraf til anvendelse i en fremgangsmåde til behandling eller forsinkelse af progressionen eller begyndelsen på diabetes type 2 og diabetes-relaterede sygdomme i dyr.
16. Farmaceutisk sammensætning ifølge et af kravene 11 til 13 til anvendelse i en fremgangsmåde til behandling eller forsinkelsen af progressionen eller begyndelsen på diabetes type 2 og diabetes-relaterede sygdomme i dyr.
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Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040198483A1 (en) 2003-04-03 2004-10-07 Amaitis Lee M. System and method for betting on a subset of participants in an event
US8636571B2 (en) 2004-02-03 2014-01-28 Cantor Index, Llc System and method for managing select five horseracing bets
US9098883B2 (en) 2004-02-03 2015-08-04 Cantor Index, Llc Managing bets that select events and participants
ES2545231T3 (es) 2008-05-28 2015-09-09 Pfizer Inc. Inhibidores de pirazoloespirocetona acetil-CoA carboxilasa
DK2499139T3 (da) 2009-11-10 2014-01-27 Pfizer N1-pyrazolospiroketon-acetyl-coa-carboxylasehæmmere
ES2602111T3 (es) 2010-09-30 2017-02-17 Pfizer Inc Inhibidores de acetil-CoA carboxilasas de N1-pirazoloespirocetona
AU2011322117B2 (en) * 2010-10-29 2015-01-22 Pfizer Inc. N1/N2-lactam acetyl-CoA carboxylase inhibitors
PL2699576T3 (pl) * 2011-04-22 2016-05-31 Pfizer Pochodne pirazolospiroketonu do zastosowania jako inhibitory karboksylazy acetylo-COA
WO2013116359A1 (en) 2012-01-30 2013-08-08 Cfph, Llc Event wagering with group and/or in run options
US11055967B2 (en) 2014-03-26 2021-07-06 Cfph, Llc Event wagering with group and/or in run options
US20170178994A1 (en) * 2015-12-21 2017-06-22 Intel Corporation Integrated circuit package support structures
KR102579876B1 (ko) 2016-02-22 2023-09-18 삼성전자주식회사 반도체 패키지
KR20190136079A (ko) * 2017-04-18 2019-12-09 장피트 엘라피브라노르와 같은 ppar 작용제 및 아세틸-coa 카르복실라아제 (acc) 저해제를 포함하는 조합
AU2018372109B2 (en) * 2017-11-21 2021-07-01 Pfizer Inc. Crystalline 2-amino-2-(hydroxymethyl)propane-1,3-diol salt of 4-(4-(1-isopropyl-7-oxo-1,4,6,7-tetrahydrospiro(indazole-5,4'-piperidine)-1'-carbonyl)-6-methoxypyridin-2-yl)benzoic acid
CA3045644C (en) 2018-06-13 2024-01-16 Pfizer Inc. Glp-1 receptor agonists and uses thereof
KR102614808B1 (ko) * 2018-08-31 2023-12-19 화이자 인코포레이티드 Nash/nafld 및 관련 질환의 치료를 위한 조합물
US20220387402A1 (en) 2019-05-20 2022-12-08 Pfizer Inc. Combinations comprising benzodioxol as glp-1r agonists for use in the treatment of nash/nafld and related diseases
CN110183456A (zh) * 2019-07-11 2019-08-30 河南师范大学 一种2-芳基吲唑琥珀酰亚胺螺环化合物的合成方法
WO2021116874A1 (en) 2019-12-10 2021-06-17 Pfizer Inc. Solid forms of 2-((4-((s)-2-(5-chloropyridin-2-yl)-2-methylbenzo[d] [1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-benzo[d] imidazole-6-carboxylic acid, 1,3-dihydroxy-2-(hydroxymethyl)propan-2-amine salt
JP2023509452A (ja) 2020-01-03 2023-03-08 バーグ エルエルシー がんを処置するためのｕｂｅ２ｋモジュレータとしての多環式アミド
JP2021134211A (ja) 2020-02-24 2021-09-13 ファイザー・インク Ｎａｆｌｄ／ｎａｓｈおよび関連疾患の処置のための組合せ
JP2022058085A (ja) 2020-02-24 2022-04-11 ファイザー・インク ジアシルグリセロールアシルトランスフェラーゼ２阻害剤とアセチル－ＣｏＡカルボキシラーゼ阻害剤との組合せ
KR20220157486A (ko) 2020-03-27 2022-11-29 화이자 인코포레이티드 2-[(4-(6-[(4-시아노-2-플루오로벤질)옥시]피리딘-2-일)피페리딘-1-일)메틸]-1-[(2s)-옥세탄-2-일메틸]-1h-벤즈이미다졸-6-카르복실산 또는 그의 제약상 염을 사용한 제2형 당뇨병 또는 비만 또는 과체중의 치료
CA3230347A1 (en) 2021-08-31 2023-03-09 Pfizer Inc. Solid forms of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2s)-oxetan-2-ylmethyl]-1h-benzimidazole-6-carboxylic acid, 1,3-dihydroxy-2-(hydroxymethyl)propan-2-amine salt
WO2023169456A1 (en) 2022-03-09 2023-09-14 Gasherbrum Bio , Inc. Heterocyclic glp-1 agonists
WO2023198140A1 (en) 2022-04-14 2023-10-19 Gasherbrum Bio, Inc. Heterocyclic glp-1 agonists
WO2023228023A1 (en) 2022-05-23 2023-11-30 Pfizer Inc. Treatment of type 2 diabetes or weight management control with 2-((4-((s)-2-(5-chloropyridin-2-yl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-benzo[d]imidazole-6-carboxylic acid or a pharmaceutically salt thereof
WO2024084360A1 (en) 2022-10-18 2024-04-25 Pfizer Inc. Patatin-like phospholipase domain-containing protein 3 (pnpla3) modifiers
WO2024125602A1 (en) 2022-12-15 2024-06-20 Gasherbrum Bio, Inc. Salts and solid forms of a compound having glp-1 agonist activity

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0901786B1 (en) 1997-08-11 2007-06-13 Pfizer Products Inc. Solid pharmaceutical dispersions with enhanced bioavailability
EP1383501B1 (en) 2001-02-28 2007-04-04 Merck & Co., Inc. Acylated piperidine derivatives as melanocortin-4 receptor agonists
AU2003248354A1 (en) 2002-02-27 2003-09-09 Pfizer Products Inc. Acc inhibitors
US7105526B2 (en) 2002-06-28 2006-09-12 Banyu Pharmaceuticals Co., Ltd. Benzimidazole derivatives
WO2004092179A1 (ja) 2003-04-14 2004-10-28 Nippon Soda Co. Ltd. スピロ誘導体、製造法および抗酸化薬
JP2005119987A (ja) 2003-10-15 2005-05-12 Ajinomoto Co Inc アシルスルホンアミド誘導体
US20050267221A1 (en) 2004-05-14 2005-12-01 Research Development Foundation Use of curcumin and analogues thereof as inhibitors of ACC2
AP2006003768A0 (en) 2004-05-25 2006-10-31 Pfizer Prod Inc TetraazabenzoÄeÜazulene derivatives and analogs tehereof
PA8660701A1 (es) 2005-02-04 2006-09-22 Pfizer Prod Inc Agonistas de pyy y sus usos
EP1910375B1 (en) 2005-07-19 2011-05-11 Merck Sharp & Dohme Corp. Spirochromanone derivatives as acetyl coenzyme a carboxylase (acc) inhibitors
JPWO2007013691A1 (ja) 2005-07-29 2009-02-12 武田薬品工業株式会社 スピロ環化合物
DE102006016566B4 (de) 2005-09-22 2008-06-12 Beru Ag Zusammengesetzter Leiter, insbesondere für Glühkerzen für Dieselmotoren
US8071770B2 (en) 2005-11-18 2011-12-06 Merck Sharp & Dohme Corp. Spirohydantoin aryl CGRP receptor antagonists
JP2009526868A (ja) 2006-02-15 2009-07-23 アボット・ラボラトリーズ 新規なアセチル−ＣｏＡカルボキシラーゼ（ＡＣＣ）阻害薬およびこれらの糖尿病、肥満および代謝症候群における使用
MX2009005604A (es) 2006-11-29 2009-06-08 Pfizer Prod Inc Inhibidores espiro cetona de acetil-coa carboxilasa.
PE20081559A1 (es) 2007-01-12 2008-11-20 Merck & Co Inc DERIVADOS DE ESPIROCROMANONA SUSTITUIDOS COMO INHIBIDORES DE ACETIL CoA CARBOXILASA
JP5271917B2 (ja) * 2007-01-12 2013-08-21 メルク・シャープ・アンド・ドーム・コーポレーション スピロクロマノン誘導体
JPWO2008102749A1 (ja) * 2007-02-20 2010-05-27 武田薬品工業株式会社 複素環化合物
MX2009010951A (es) 2007-04-12 2009-10-29 Pfizer Derivados de 3-amino-pirrolo[3,4-c]pirazol-5(1h,4h,6h)-carbaldehid o como inhibidores de proteina quinasa c.
US7981904B2 (en) 2008-03-20 2011-07-19 Takeda Pharmaceutical Company Limited Acetyl CoA carboxylase inhibitors
ES2545231T3 (es) 2008-05-28 2015-09-09 Pfizer Inc. Inhibidores de pirazoloespirocetona acetil-CoA carboxilasa
US20110009443A1 (en) 2008-05-28 2011-01-13 Kevin Daniel Freeman-Cook Pyrazolospiroketone Acetyl-Coa Carboxylase Inhibitors
CA2729412A1 (en) * 2008-07-04 2010-01-07 Banyu Pharmaceutical Co., Ltd. Novel spirochromanone carboxylic acids
JP2011528034A (ja) 2008-07-14 2011-11-10 クロップソリューション，インコーポレイテッド アセチル−補酵素カルボキシラーゼの修飾因子およびその使用方法
WO2011058473A1 (en) * 2009-11-10 2011-05-19 Pfizer Inc. N2-pyrazolospiroketone acetyl-coa carboxylase inhibitors
DK2499139T3 (da) * 2009-11-10 2014-01-27 Pfizer N1-pyrazolospiroketon-acetyl-coa-carboxylasehæmmere
ES2602111T3 (es) * 2010-09-30 2017-02-17 Pfizer Inc Inhibidores de acetil-CoA carboxilasas de N1-pirazoloespirocetona
US20160034775A1 (en) 2014-08-02 2016-02-04 General Vault, LLC Methods and apparatus for bounded image data analysis and notification mechanism

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