RU2692102C2 - 2,2,2-трифторэтил-тиадиазины - Google Patents
2,2,2-трифторэтил-тиадиазины Download PDFInfo
- Publication number
- RU2692102C2 RU2692102C2 RU2017107495A RU2017107495A RU2692102C2 RU 2692102 C2 RU2692102 C2 RU 2692102C2 RU 2017107495 A RU2017107495 A RU 2017107495A RU 2017107495 A RU2017107495 A RU 2017107495A RU 2692102 C2 RU2692102 C2 RU 2692102C2
- Authority
- RU
- Russia
- Prior art keywords
- thiadiazin
- oxo
- fluoropyridin
- dimethyl
- trifluoroethylimino
- Prior art date
Links
- KJHPOHPHXKIEEH-UHFFFAOYSA-N 4-(2,2,2-trifluoroethyl)-2H-thiadiazine Chemical class FC(CC1=NNSC=C1)(F)F KJHPOHPHXKIEEH-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 161
- -1 cyano, methyl Chemical group 0.000 claims abstract description 102
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 28
- 102100021257 Beta-secretase 1 Human genes 0.000 claims abstract description 19
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 17
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 claims abstract description 16
- 230000000694 effects Effects 0.000 claims abstract description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims abstract description 6
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 41
- 238000011321 prophylaxis Methods 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
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- KCWCNAKODOEVQE-WUTYVCDSSA-N NC=1N(S(C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1C)C#N)F)(=O)=NC)CC(F)(F)F Chemical compound NC=1N(S(C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1C)C#N)F)(=O)=NC)CC(F)(F)F KCWCNAKODOEVQE-WUTYVCDSSA-N 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 7
- IQNFOMCQCZMGLC-HJFSHJIFSA-N (1R,5R)-5-[3-fluoro-6-(1H-pyrazol-5-yl)pyridin-2-yl]-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-3-amine Chemical compound FC=1C(=NC(=CC=1)C1=CC=NN1)[C@]1(N=C(N([S@@](C1)(=NCC(F)(F)F)=O)C)N)C IQNFOMCQCZMGLC-HJFSHJIFSA-N 0.000 claims description 5
- ZVOYHRVXWDOKFR-PEGYKEAPSA-N (1R,5R)-5-[6-(5-chlorothiophen-2-yl)-3-fluoropyridin-2-yl]-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-3-amine Chemical compound ClC1=CC=C(S1)C1=CC=C(C(=N1)[C@]1(N=C(N([S@@](C1)(=NCC(F)(F)F)=O)C)N)C)F ZVOYHRVXWDOKFR-PEGYKEAPSA-N 0.000 claims description 5
- ZBTYNHZFTNANRV-BUBHHJDNSA-N BrC1=CC=C(C(=N1)[C@]1(N=C(N([S@](C1)(=NCC(F)(F)F)=O)C)N)C)F Chemical compound BrC1=CC=C(C(=N1)[C@]1(N=C(N([S@](C1)(=NCC(F)(F)F)=O)C)N)C)F ZBTYNHZFTNANRV-BUBHHJDNSA-N 0.000 claims description 5
- DQSOWIVDGKTGAW-DCDFMGFMSA-N N-[6-[(1R,5R)-3-amino-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-5-yl]-5-fluoropyridin-2-yl]-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxamide Chemical compound NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1)OCC(F)(F)F)F)(=NCC(F)(F)F)=O)C DQSOWIVDGKTGAW-DCDFMGFMSA-N 0.000 claims description 5
- YOLGMDARIPFAQD-SRKBSBODSA-N N-[6-[(1R,5R)-3-amino-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-5-yl]-5-fluoropyridin-2-yl]-5-(fluoromethoxy)pyridine-2-carboxamide Chemical compound NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1)OCF)F)(=NCC(F)(F)F)=O)C YOLGMDARIPFAQD-SRKBSBODSA-N 0.000 claims description 5
- NUVYICOKNIIFEN-JTHIVGNPSA-N N-[6-[(1R,5R)-3-amino-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-5-yl]-5-fluoropyridin-2-yl]-5-but-2-ynoxypyrazine-2-carboxamide Chemical compound NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(N=C1)OCC#CC)F)(=NCC(F)(F)F)=O)C NUVYICOKNIIFEN-JTHIVGNPSA-N 0.000 claims description 5
- CUQYOKPNIRBTAZ-HSVJZKSBSA-N N-[6-[(1R,5R)-3-amino-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-5-yl]-5-fluoropyridin-2-yl]-5-cyano-3-methylpyridine-2-carboxamide Chemical compound NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1C)C#N)F)(=NCC(F)(F)F)=O)C CUQYOKPNIRBTAZ-HSVJZKSBSA-N 0.000 claims description 5
- MBZBTDINMMUJLX-USXNREEHSA-N N-[6-[(1R,5R)-3-amino-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-5-yl]-5-fluoropyridin-2-yl]-5-cyanopyridine-2-carboxamide Chemical compound NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1)C#N)F)(=NCC(F)(F)F)=O)C MBZBTDINMMUJLX-USXNREEHSA-N 0.000 claims description 5
- UZOYZJDFERWLPF-USXNREEHSA-N N-[6-[(1R,5R)-3-amino-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-5-yl]-5-fluoropyridin-2-yl]-5-fluoro-3-methylpyridine-2-carboxamide Chemical compound NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1C)F)F)(=NCC(F)(F)F)=O)C UZOYZJDFERWLPF-USXNREEHSA-N 0.000 claims description 5
- RYOMQTOPQKEDSX-TXULOHPCSA-N N-[6-[(1R,5R)-3-amino-2,5-dimethyl-1-oxo-1-(2,2,2-trifluoroethylimino)-6H-1,2,4-thiadiazin-5-yl]-5-fluoropyridin-2-yl]-5-methoxypyrazine-2-carboxamide Chemical compound NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(N=C1)OC)F)(=NCC(F)(F)F)=O)C RYOMQTOPQKEDSX-TXULOHPCSA-N 0.000 claims description 5
- VQRZLLKYMXQQIK-PTIIMASVSA-N NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1)OCC#C)F)(=NCC(F)(F)F)=O)C Chemical compound NC=1N([S@@](C[C@@](N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1)OCC#C)F)(=NCC(F)(F)F)=O)C VQRZLLKYMXQQIK-PTIIMASVSA-N 0.000 claims description 5
- KCWCNAKODOEVQE-UHFFFAOYSA-N NC=1N(S(CC(N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1C)C#N)F)(=O)=NC)CC(F)(F)F Chemical compound NC=1N(S(CC(N=1)(C)C1=C(C=CC(=N1)NC(=O)C1=NC=C(C=C1C)C#N)F)(=O)=NC)CC(F)(F)F KCWCNAKODOEVQE-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
- 235000019801 trisodium phosphate Nutrition 0.000 description 1
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14181123 | 2014-08-15 | ||
| EP14181123.2 | 2014-08-15 | ||
| PCT/EP2015/068506 WO2016023927A1 (en) | 2014-08-15 | 2015-08-12 | 2,2,2-trifluoroethyl-thiadiazines |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2017107495A RU2017107495A (ru) | 2018-09-17 |
| RU2017107495A3 RU2017107495A3 (https=) | 2019-02-25 |
| RU2692102C2 true RU2692102C2 (ru) | 2019-06-21 |
Family
ID=51302940
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2017107495A RU2692102C2 (ru) | 2014-08-15 | 2015-08-12 | 2,2,2-трифторэтил-тиадиазины |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US9896438B2 (https=) |
| EP (1) | EP3180330B1 (https=) |
| JP (1) | JP6543697B2 (https=) |
| KR (1) | KR20170043581A (https=) |
| CN (1) | CN106459006B (https=) |
| BR (1) | BR112016026814A8 (https=) |
| CA (1) | CA2952160A1 (https=) |
| MX (1) | MX375329B (https=) |
| RU (1) | RU2692102C2 (https=) |
| WO (1) | WO2016023927A1 (https=) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109180672A (zh) * | 2018-09-29 | 2019-01-11 | 广东东阳光药业有限公司 | 亚氨基噻二嗪二氧化物衍生物及其用途 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2162087C2 (ru) * | 1995-01-11 | 2001-01-20 | Мерк Патент Гмбх | 3-алкоксикарбонил-тиадиазиноны, способ их получения и фармацевтическая композиция |
| WO2011044184A1 (en) * | 2009-10-08 | 2011-04-14 | Schering Corporation | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| WO2011044181A1 (en) * | 2009-10-08 | 2011-04-14 | Schering Corporation | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014150331A1 (en) * | 2013-03-15 | 2014-09-25 | Merck Sharp & Dohme Corp. | S-imino-s-oxo iminothiazine compounds as bace inhibitors, compositions, and their use |
| US9428476B2 (en) * | 2013-03-15 | 2016-08-30 | Merck Sharp & Dohme Corp. | S-imino-S-oxo-iminothiadiazine compounds as BACE inhibitors, compositions, and their use |
| CN105683199B (zh) * | 2013-12-20 | 2018-06-26 | 豪夫迈·罗氏有限公司 | 5-芳基-1-亚氨基-1-氧代-[1，2，4]噻二嗪 |
-
2015
- 2015-08-12 US US15/502,044 patent/US9896438B2/en not_active Expired - Fee Related
- 2015-08-12 RU RU2017107495A patent/RU2692102C2/ru active
- 2015-08-12 MX MX2016016061A patent/MX375329B/es active IP Right Grant
- 2015-08-12 KR KR1020177006946A patent/KR20170043581A/ko not_active Ceased
- 2015-08-12 EP EP15748252.2A patent/EP3180330B1/en not_active Not-in-force
- 2015-08-12 JP JP2017506993A patent/JP6543697B2/ja not_active Expired - Fee Related
- 2015-08-12 WO PCT/EP2015/068506 patent/WO2016023927A1/en not_active Ceased
- 2015-08-12 CN CN201580032183.8A patent/CN106459006B/zh not_active Expired - Fee Related
- 2015-08-12 BR BR112016026814A patent/BR112016026814A8/pt active Search and Examination
- 2015-08-12 CA CA2952160A patent/CA2952160A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2162087C2 (ru) * | 1995-01-11 | 2001-01-20 | Мерк Патент Гмбх | 3-алкоксикарбонил-тиадиазиноны, способ их получения и фармацевтическая композиция |
| WO2011044184A1 (en) * | 2009-10-08 | 2011-04-14 | Schering Corporation | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
| WO2011044181A1 (en) * | 2009-10-08 | 2011-04-14 | Schering Corporation | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6543697B2 (ja) | 2019-07-10 |
| US20170226091A1 (en) | 2017-08-10 |
| EP3180330B1 (en) | 2021-03-03 |
| CA2952160A1 (en) | 2016-02-18 |
| MX2016016061A (es) | 2017-03-10 |
| BR112016026814A2 (pt) | 2017-08-15 |
| WO2016023927A1 (en) | 2016-02-18 |
| BR112016026814A8 (pt) | 2021-07-20 |
| MX375329B (es) | 2025-03-06 |
| KR20170043581A (ko) | 2017-04-21 |
| CN106459006A (zh) | 2017-02-22 |
| EP3180330A1 (en) | 2017-06-21 |
| CN106459006B (zh) | 2020-02-11 |
| US9896438B2 (en) | 2018-02-20 |
| RU2017107495A3 (https=) | 2019-02-25 |
| RU2017107495A (ru) | 2018-09-17 |
| JP2017524006A (ja) | 2017-08-24 |
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