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DK3160948T3 - Benzoxazinonamider som modulatorer af mineralocorticoidreceptorer - Google Patents

Benzoxazinonamider som modulatorer af mineralocorticoidreceptorer Download PDF

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Publication number
DK3160948T3
DK3160948T3 DK15736015.7T DK15736015T DK3160948T3 DK 3160948 T3 DK3160948 T3 DK 3160948T3 DK 15736015 T DK15736015 T DK 15736015T DK 3160948 T3 DK3160948 T3 DK 3160948T3
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Prior art keywords
benzoxazin
dihydro
oxo
mmol
compound
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DK15736015.7T
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English (en)
Inventor
Gavin O'mahony
Michael Kossenjans
Karl Edman
Johan Kajanus
Carl Anders Hogner
Philip Cornwall
Andrew Turner
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Astrazeneca Ab
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D265/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/281,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/341,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/361,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/5381,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Claims (10)

1. Forbindelse med formlen (I) dXu HN? o hvori: R1 er valgt blandt CONH2 og CONHCH3, og R2 er valgt blandt H, F, Cl og Br eller et farmaceutisk acceptabelt salt deraf.
2. Forbindelse ifølge krav 1 eller farmaceutisk acceptabelt salt deraf, hvori: R1 er CONHCH3, og R2 er valgt blandt H, F, Cl og Br.
3. Forbindelse ifølge krav 1 eller farmaceutisk acceptabelt salt deraf, hvori: R1 er CONHCH3, og R2 er F.
4. Forbindelse ifølge krav 1, der er valgt blandt: 2 —{4 —[ (3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl)carbonyl]-3,4- dihydro-2H-l,4-benzoxazin-3-yl} acetamid N-methyl-2-{4 —[ (3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid N-methyl-2-{ (3S)—4—[ (3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid N-methyl-2-{(3R)-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{7-fluor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{(3S)-7-fluor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{(3R)-7-fluor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{7-fluor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl] - 3,4-dihydro-2H-l, 4-benzoxazin-3-yl} -limet hyl acet amid 2-{ (3S)-7-fluor-4-[ (3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl] - 3,4-dihydro-2H-l, 4-benzoxazin-3-yl} -lime thy lace t amid 2-{(3R)-7-fluor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl] - 3,4-dihydro-2H-l, 4-benzoxazin-3-yl} -lime thy lace t amid 2-{7-chlor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{(3S)-7-chlor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{(3R)-7-chlor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{7-chlor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl] - 3,4-dihydro-2H-l, 4-benzoxazin-3-yl} -lime thy lace t amid 2-{ (3S)-7-chlor-4-[ (3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl] - 3,4-dihydro-2H-l, 4-benzoxazin-3-yl} -lime thy lace t amid 2-{(3R)-7-chlor-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl] - 3,4-dihydro-2H-l, 4-benzoxazin-3-yl} -lime thy lace t amid 2-{7-brom-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{ (3 S)-7-brom-4-[ (3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{(3R)-7-brom-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}acetamid 2-{7-brom-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl) carbonyl] - 3,4-dihydro-2H-l, 4-benzoxazin-3-yl} -lime thy lace t amid 2-{ (3 S)-7-brom-4-[ (3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl) carbonyl] - 3,4-dihydro-2H-l, 4-benzoxazin-3-yl} -lime thy lace t amid 2-{(3R)-7-brom-4-[(3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6- yl)carbonyl]-3,4-dihydro-2H-l,4-benzoxazin-3-yl}-N-methylacetamid eller et farmaceutisk acceptabelt salt deraf.
5. Forbindelse ifølge krav 1, som er 2-{ (3S)-7-fluor-4-[ (3-oxo-3,4-dihydro-2H-l,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}-N-methylacetamid.
6. Farmaceutisk formulering, der omfatter en forbindelse med formlen (I) eller et farmaceutisk acceptabelt salt af en forbindelse med formlen (I) ifølge et hvilket som helst af kravene 1 til 5 og en farmaceutisk acceptabel bærer, excipiens eller fortyndingsmiddel
7. Forbindelse med formel (I) eller et farmaceutisk acceptabelt salt af en forbindelse med formlen (I) ifølge et hvilket som helst af kravene 1 til 5 til anvendelse inden for terapi.
8. Forbindelse med formel (I) eller et farmaceutisk acceptabelt salt af en forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 5 til anvendelse inden for behandling og/eller forebyggelse af kardiovaskulær sygdom.
9. Forbindelse til anvendelse ifølge krav 8, hvori den kardiovaskulære sygdom er hjertesvigt.
10. Forbindelse med formel (I) eller et farmaceutisk acceptabelt salt af en forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 5 til anvendelse inden for behandling og/eller forebyggelse af kronisk nyresygdom.
DK15736015.7T 2014-06-30 2015-06-26 Benzoxazinonamider som modulatorer af mineralocorticoidreceptorer DK3160948T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462018790P 2014-06-30 2014-06-30
PCT/GB2015/051860 WO2016001631A1 (en) 2014-06-30 2015-06-26 Benzoxazinone amides as mineralocorticoid receptor modulators

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US (2) US10017502B2 (da)
EP (1) EP3160948B1 (da)
JP (1) JP6368383B2 (da)
KR (1) KR102012222B1 (da)
CN (1) CN106536491B (da)
AR (1) AR101036A1 (da)
AU (1) AU2015282450C1 (da)
CA (1) CA2953655C (da)
CY (1) CY1121596T1 (da)
DK (1) DK3160948T3 (da)
EA (1) EA029518B1 (da)
ES (1) ES2707726T3 (da)
HR (1) HRP20190147T1 (da)
HU (1) HUE042370T2 (da)
LT (1) LT3160948T (da)
ME (1) ME03316B (da)
MX (1) MX367404B (da)
PL (1) PL3160948T3 (da)
PT (1) PT3160948T (da)
RS (1) RS58274B1 (da)
SI (1) SI3160948T1 (da)
SM (1) SMT201900039T1 (da)
TR (1) TR201900659T4 (da)
TW (1) TWI677498B (da)
UY (1) UY36195A (da)
WO (1) WO2016001631A1 (da)

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PL3160948T3 (pl) * 2014-06-30 2019-04-30 Astrazeneca Ab Amidy benzoksazynonu jako modulatory receptorów mineralokortykoidowych
AU2019304032B2 (en) 2018-07-19 2021-12-09 Astrazeneca Ab Methods of treating HFpEF employing dapagliflozin and compositions comprising the same
CN112107568B (zh) * 2019-06-19 2022-03-25 北京龙嘉博创医药科技有限公司 二芳基酰胺类化合物及其应用
EP4021507A1 (en) * 2019-08-30 2022-07-06 AstraZeneca AB Methods of treating heart failure with reduced ejection fraction with dapagliflozin
WO2022022865A1 (en) 2020-07-27 2022-02-03 Astrazeneca Ab Methods of treating chronic kidney disease with dapagliflozin
MX2023015144A (es) * 2021-06-15 2024-01-22 Chia Tai Tianqing Pharmaceutical Group Co Ltd Derivados de benzoxazinona.
TW202409023A (zh) 2022-07-14 2024-03-01 美商富曼西公司 除草苯并𠯤
IL319212A (en) 2022-09-01 2025-04-01 Astrazeneca Ab Combination of SGLT2 inhibitors and mineralocorticoid receptor modulators for use in the treatment of heart and kidney disease
WO2024125591A1 (zh) * 2022-12-15 2024-06-20 正大天晴药业集团股份有限公司 苯并恶嗪酮类化合物的结晶及其制备
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US10017502B2 (en) 2018-07-10
CA2953655C (en) 2020-05-12
RS58274B1 (sr) 2019-03-29
CY1121596T1 (el) 2020-05-29
KR102012222B1 (ko) 2019-10-21
AU2015282450C1 (en) 2018-09-20
KR20170021883A (ko) 2017-02-28
ES2707726T3 (es) 2019-04-04
US9394291B2 (en) 2016-07-19
UY36195A (es) 2016-01-08
EA029518B1 (ru) 2018-04-30
JP2017522300A (ja) 2017-08-10
ME03316B (me) 2019-10-20
MX2017000183A (es) 2017-04-25
EP3160948B1 (en) 2018-10-24
HRP20190147T1 (hr) 2019-03-22
CN106536491A (zh) 2017-03-22
TR201900659T4 (tr) 2019-02-21
EP3160948A1 (en) 2017-05-03
SI3160948T1 (sl) 2020-06-30
PT3160948T (pt) 2019-02-01
JP6368383B2 (ja) 2018-08-01
US20150376170A1 (en) 2015-12-31
US20170217945A1 (en) 2017-08-03
EA201790046A1 (ru) 2017-08-31
WO2016001631A1 (en) 2016-01-07
CA2953655A1 (en) 2016-01-07
AU2015282450A1 (en) 2017-02-02
SMT201900039T1 (it) 2019-02-28
PL3160948T3 (pl) 2019-04-30
AU2015282450B2 (en) 2018-05-10
TWI677498B (zh) 2019-11-21
TW201613909A (en) 2016-04-16
CN106536491B (zh) 2018-12-18
LT3160948T (lt) 2019-02-11
MX367404B (es) 2019-08-20
AR101036A1 (es) 2016-11-16
HUE042370T2 (hu) 2019-06-28

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