KR20180053408A - 이중 오토탁신(atx)/탄산 무수화효소(ca) 억제제로서의 신규한 이환형 화합물 - Google Patents
이중 오토탁신(atx)/탄산 무수화효소(ca) 억제제로서의 신규한 이환형 화합물 Download PDFInfo
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- KR20180053408A KR20180053408A KR1020187011566A KR20187011566A KR20180053408A KR 20180053408 A KR20180053408 A KR 20180053408A KR 1020187011566 A KR1020187011566 A KR 1020187011566A KR 20187011566 A KR20187011566 A KR 20187011566A KR 20180053408 A KR20180053408 A KR 20180053408A
- Authority
- KR
- South Korea
- Prior art keywords
- substituted
- alkyl
- alkoxy
- pyrrole
- pyridinyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 127
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- 108090000209 Carbonic anhydrases Proteins 0.000 title description 12
- 239000003112 inhibitor Substances 0.000 title description 6
- 238000000034 method Methods 0.000 claims abstract description 47
- -1 -C 2-6 - alkenyl Chemical group 0.000 claims description 134
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 59
- 125000004076 pyridyl group Chemical group 0.000 claims description 57
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 32
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- 238000006243 chemical reaction Methods 0.000 claims description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 14
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
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- VMVMHHKCHQENQR-IERDGZPVSA-N FC(OC1=CC=C(COC(=O)N2C[C@H]3CN(C[C@@]3(C2)F)C(C2=CC=C(C=C2)S(N)(=O)=O)=O)C=C1)(F)F Chemical compound FC(OC1=CC=C(COC(=O)N2C[C@H]3CN(C[C@@]3(C2)F)C(C2=CC=C(C=C2)S(N)(=O)=O)=O)C=C1)(F)F VMVMHHKCHQENQR-IERDGZPVSA-N 0.000 claims description 6
- VIABIWADPYYFDB-VGSWGCGISA-N FC(OC1=CC=C(COC(=O)N2C[C@H]3CN(C[C@@]3(C2)OC)C(C2=CC=C(C=C2)S(N)(=O)=O)=O)C=C1)(F)F Chemical compound FC(OC1=CC=C(COC(=O)N2C[C@H]3CN(C[C@@]3(C2)OC)C(C2=CC=C(C=C2)S(N)(=O)=O)=O)C=C1)(F)F VIABIWADPYYFDB-VGSWGCGISA-N 0.000 claims description 6
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- NKFLEFWUYAUDJV-UHFFFAOYSA-N pyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1 NKFLEFWUYAUDJV-UHFFFAOYSA-N 0.000 claims description 6
- 150000003222 pyridines Chemical class 0.000 claims description 6
- ZMKCKGYEYDGHPN-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]methyl 4-fluoro-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound FC(OC1=CC=C(COC(=O)N2C(C3CNCC3C2)F)C=C1)(F)F ZMKCKGYEYDGHPN-UHFFFAOYSA-N 0.000 claims description 4
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- AAICNDKQIKYSNG-QZZOKCEJSA-N 4-[(3aR,6aS)-3a-fluoro-2-[(E)-3-[4-(trifluoromethoxy)phenyl]prop-2-enoyl]-3,4,6,6a-tetrahydro-1H-pyrrolo[3,4-c]pyrrole-5-carbonyl]-3-fluorobenzenesulfonamide Chemical compound F[C@@]12[C@H](CN(C1)C(=O)C1=C(C=C(C=C1)S(=O)(=O)N)F)CN(C2)C(\C=C\C1=CC=C(C=C1)OC(F)(F)F)=O AAICNDKQIKYSNG-QZZOKCEJSA-N 0.000 claims description 3
- BGHGKELMYMNCFY-JTSKRJEESA-N FC(OC1=CC=C(COC(=O)N2C[C@@H]3CN(C[C@]3(C2)C)C(C2=CC=C(C=C2)S(N)(=O)=O)=O)C=C1)(F)F Chemical compound FC(OC1=CC=C(COC(=O)N2C[C@@H]3CN(C[C@]3(C2)C)C(C2=CC=C(C=C2)S(N)(=O)=O)=O)C=C1)(F)F BGHGKELMYMNCFY-JTSKRJEESA-N 0.000 claims description 3
- BGHGKELMYMNCFY-VGOFRKELSA-N FC(OC1=CC=C(COC(=O)N2C[C@H]3CN(C[C@@]3(C2)C)C(C2=CC=C(C=C2)S(N)(=O)=O)=O)C=C1)(F)F Chemical compound FC(OC1=CC=C(COC(=O)N2C[C@H]3CN(C[C@@]3(C2)C)C(C2=CC=C(C=C2)S(N)(=O)=O)=O)C=C1)(F)F BGHGKELMYMNCFY-VGOFRKELSA-N 0.000 claims description 3
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
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- 150000001412 amines Chemical class 0.000 description 39
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 239000000543 intermediate Substances 0.000 description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 22
- WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 description 20
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 20
- 125000000217 alkyl group Chemical group 0.000 description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 19
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 17
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- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15186642 | 2015-09-24 | ||
| EP15186642.3 | 2015-09-24 | ||
| PCT/EP2016/072277 WO2017050747A1 (en) | 2015-09-24 | 2016-09-20 | New bicyclic compounds as dual atx/ca inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20180053408A true KR20180053408A (ko) | 2018-05-21 |
Family
ID=54199040
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020187011566A Withdrawn KR20180053408A (ko) | 2015-09-24 | 2016-09-20 | 이중 오토탁신(atx)/탄산 무수화효소(ca) 억제제로서의 신규한 이환형 화합물 |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US10738053B2 (OSRAM) |
| EP (1) | EP3353181B1 (OSRAM) |
| JP (1) | JP6845230B2 (OSRAM) |
| KR (1) | KR20180053408A (OSRAM) |
| CN (1) | CN107614505B (OSRAM) |
| AR (1) | AR106100A1 (OSRAM) |
| AU (1) | AU2016328365B2 (OSRAM) |
| BR (1) | BR112017026682A2 (OSRAM) |
| CA (1) | CA2984585A1 (OSRAM) |
| CL (1) | CL2018000649A1 (OSRAM) |
| CO (1) | CO2017011152A2 (OSRAM) |
| CR (1) | CR20180143A (OSRAM) |
| IL (1) | IL255511B (OSRAM) |
| MX (1) | MX2017015034A (OSRAM) |
| PE (1) | PE20180233A1 (OSRAM) |
| PH (1) | PH12018500409A1 (OSRAM) |
| RU (1) | RU2725138C2 (OSRAM) |
| TW (1) | TW201725206A (OSRAM) |
| WO (1) | WO2017050747A1 (OSRAM) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN2014DN09346A (OSRAM) | 2012-06-13 | 2015-07-17 | Hoffmann La Roche | |
| MA37940B1 (fr) | 2012-09-25 | 2018-09-28 | Hoffmann La Roche | Derives d'octahydro-cyclopenta(c)pyrrole substitues inhibiteurs de l'autotaxine, utiles pour traiter les affections renales, hepatiques et inflammatoires, les affections du systeme nerveux, les maladies fibreuses. |
| AR095079A1 (es) | 2013-03-12 | 2015-09-16 | Hoffmann La Roche | Derivados de octahidro-pirrolo[3,4-c]-pirrol y piridina-fenilo |
| UA118201C2 (uk) | 2013-11-26 | 2018-12-10 | Ф. Хоффманн-Ля Рош Аг | НОВИЙ ОКТАГІДРОЦИКЛОБУТА[1,2-c;3,4-c']ДИПІРОЛ-2-ІЛ |
| EP3590939A1 (en) | 2014-03-26 | 2020-01-08 | F. Hoffmann-La Roche AG | Bicyclic compounds as autotaxin (atx) and lysophosphatidic acid (lpa) production inhibitors |
| WO2015144609A1 (en) | 2014-03-26 | 2015-10-01 | F. Hoffmann-La Roche Ag | Condensed [1,4]diazepine compounds as autotaxin (atx) and lysophosphatidic acid (lpa) production inhibitors |
| MA41898A (fr) | 2015-04-10 | 2018-02-13 | Hoffmann La Roche | Dérivés de quinazolinone bicyclique |
| PE20180479A1 (es) | 2015-09-04 | 2018-03-07 | Hoffmann La Roche | Nuevos derivados de fenoximetilo |
| MX2018002217A (es) * | 2015-09-24 | 2018-03-23 | Hoffmann La Roche | Nuevos compuestos biciclicos como inhibidores de autotaxina (atx). |
| CR20180057A (es) * | 2015-09-24 | 2018-04-02 | Hoffmann La Roche | Nuevos compuestos biciclicos como inhibidores duales de atx/ca. |
| CA2984585A1 (en) | 2015-09-24 | 2017-03-30 | F. Hoffmann-La Roche Ag | New bicyclic compounds as dual atx/ca inhibitors |
| PE20180451A1 (es) | 2015-09-24 | 2018-03-05 | Hoffmann La Roche | Nuevos compuestos biciclicos como inhibidores de atx |
| RU2019132254A (ru) | 2017-03-16 | 2021-04-16 | Ф. Хоффманн-Ля Рош Аг | Гетероциклические соединения, пригодные в качестве дуальных ингибиторов atx/ca |
| EP3596060B1 (en) | 2017-03-16 | 2023-09-20 | F. Hoffmann-La Roche AG | New bicyclic compounds as atx inhibitors |
| JP7240554B2 (ja) | 2019-07-22 | 2023-03-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 炎症性気道疾患又は線維性疾患の治療のためのオートタキシン（ａｔｘ）モジュレーターとしてのｎ－メチル，１－（６－（メトキシ）ピリダジン－３－イル）アミン誘導体 |
| KR20230128511A (ko) | 2021-01-05 | 2023-09-05 | 자이두스 라이프사이언시즈 리미티드 | 신규한 오토택신 억제제 |
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2016
- 2016-09-20 CA CA2984585A patent/CA2984585A1/en not_active Abandoned
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