CA2837084C - 4h-thieno[3,2-c]chromene-based inhibitors of notum pectinacetylesterase and methods of their use - Google Patents
4h-thieno[3,2-c]chromene-based inhibitors of notum pectinacetylesterase and methods of their use Download PDFInfo
- Publication number
- CA2837084C CA2837084C CA2837084A CA2837084A CA2837084C CA 2837084 C CA2837084 C CA 2837084C CA 2837084 A CA2837084 A CA 2837084A CA 2837084 A CA2837084 A CA 2837084A CA 2837084 C CA2837084 C CA 2837084C
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- CA
- Canada
- Prior art keywords
- thieno
- carboxylic acid
- thiophene
- dihydronaphtho
- carboxamide
- 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.)
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- 102000004251 pectinacetylesterase Human genes 0.000 title abstract description 4
- 108010072638 pectinacetylesterase Proteins 0.000 title abstract description 4
- 239000003112 inhibitor Substances 0.000 title description 6
- RKKRFHATXGHKTE-UHFFFAOYSA-N 4h-thieno[3,2-c]chromene Chemical compound C1OC2=CC=CC=C2C2=C1C=CS2 RKKRFHATXGHKTE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 90
- 239000000203 mixture Substances 0.000 claims abstract description 36
- -1 nitro, sulfanyl Chemical group 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
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- 210000002307 prostate Anatomy 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
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- 239000008213 purified water Substances 0.000 description 1
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- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- DATJETPTDKFEEF-UHFFFAOYSA-N pyrrolidine-3-carbonitrile Chemical compound N#CC1CCNC1 DATJETPTDKFEEF-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229950002818 relacatib Drugs 0.000 description 1
- 239000000837 restrainer Substances 0.000 description 1
- 238000010242 retro-orbital bleeding Methods 0.000 description 1
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- 229940089617 risedronate Drugs 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000012363 selectfluor Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- SGAKODIXAHVUKL-LFELFHSZSA-M sodium;(2s,3s)-3-[[(2s)-4-methyl-1-(2-methylpropoxy)pentan-2-yl]carbamoyl]oxirane-2-carboxylate Chemical compound [Na+].CC(C)COC[C@H](CC(C)C)NC(=O)[C@H]1O[C@@H]1C([O-])=O SGAKODIXAHVUKL-LFELFHSZSA-M 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
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- 239000012453 solvate Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 1
- HHMKTQQAPCZABN-UHFFFAOYSA-N thiepine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC=CS1 HHMKTQQAPCZABN-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
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- 125000003944 tolyl group Chemical group 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- RZVSWISDVXUSGY-UHFFFAOYSA-K trisodium;8-octanoyloxypyrene-1,3,6-trisulfonate Chemical compound [Na+].[Na+].[Na+].C1=C2C(OC(=O)CCCCCCC)=CC(S([O-])(=O)=O)=C(C=C3)C2=C2C3=C(S([O-])(=O)=O)C=C(S([O-])(=O)=O)C2=C1 RZVSWISDVXUSGY-UHFFFAOYSA-K 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010451 viral insertion Methods 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000008136 water-miscible vehicle Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161490839P | 2011-05-27 | 2011-05-27 | |
| US61/490,839 | 2011-05-27 | ||
| PCT/US2012/039087 WO2012166458A1 (en) | 2011-05-27 | 2012-05-23 | 4h-thieno[3,2-c]chromene-based inhibitors of notum pectinacetylesterase and methods of their use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2837084A1 CA2837084A1 (en) | 2012-12-06 |
| CA2837084C true CA2837084C (en) | 2019-09-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2837084A Active CA2837084C (en) | 2011-05-27 | 2012-05-23 | 4h-thieno[3,2-c]chromene-based inhibitors of notum pectinacetylesterase and methods of their use |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US20120302562A1 (enExample) |
| EP (1) | EP2714675B1 (enExample) |
| JP (1) | JP6166718B2 (enExample) |
| CN (1) | CN103649072A (enExample) |
| AU (1) | AU2012262748B2 (enExample) |
| CA (1) | CA2837084C (enExample) |
| DK (1) | DK2714675T3 (enExample) |
| ES (1) | ES2715832T3 (enExample) |
| HU (1) | HUE043221T2 (enExample) |
| PL (1) | PL2714675T3 (enExample) |
| PT (1) | PT2714675T (enExample) |
| WO (1) | WO2012166458A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2012262748B2 (en) * | 2011-05-27 | 2017-03-02 | Lexicon Pharmaceuticals, Inc. | 4H-thieno[3,2-c]chromene-based inhibitors of Notum Pectinacetylesterase and methods of their use |
| KR102836360B1 (ko) | 2016-04-15 | 2025-07-23 | 베크만 컬터, 인코포레이티드 | 광활성 거대분자 및 그의 용도 |
| WO2019044946A1 (ja) | 2017-08-31 | 2019-03-07 | 第一三共株式会社 | 抗体－薬物コンジュゲートの新規製造方法 |
| CN108948011A (zh) * | 2018-08-14 | 2018-12-07 | 华南农业大学 | 一种普拉多沙星的制备方法 |
| GB201814151D0 (en) | 2018-08-31 | 2018-10-17 | Ucl Business Plc | Compounds |
| CN109134493A (zh) * | 2018-09-19 | 2019-01-04 | 浙江师范大学 | 一种具有抗菌活性的2-氧代色烯并噻吩衍生物及其合成方法和应用 |
| CN112094182B (zh) * | 2020-09-22 | 2021-11-12 | 中国海洋大学 | 一种医药中间体苯并环己酮化合物的绿色合成方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1917601C3 (de) * | 1969-04-05 | 1980-09-25 | Bayer Ag, 5090 Leverkusen | Benzoxazolyl-(2)-dihydronaphtho [4,5-b] thiophene und deren Verwendung als optische Aufheller |
| DE2628878A1 (de) * | 1976-06-26 | 1978-01-05 | Bayer Ag | Beschichtungszusammensetzung |
| US4487778A (en) * | 1983-01-27 | 1984-12-11 | Fmc Corporation | Insecticidal esters derived from benzocycloalkane-thiophenemethyl compounds |
| GB8504702D0 (en) * | 1985-02-23 | 1985-03-27 | Zyma Sa | Tricyclic compounds |
| US6080576A (en) | 1998-03-27 | 2000-06-27 | Lexicon Genetics Incorporated | Vectors for gene trapping and gene activation |
| FR2790959B1 (fr) | 1999-03-15 | 2003-06-27 | Pf Medicament | Utilisation de fractions membranaires bacteriennes a effet adjuvant, leurs procedes de preparation et composition pharmaceutique les contenant |
| UY26026A1 (es) * | 1999-03-16 | 2000-10-31 | Smithkline Beecham Corportion | Inhibidores de proteasas |
| GB0012362D0 (en) * | 2000-05-22 | 2000-07-12 | Aventis Pharma Ltd | Chemical compounds |
| JP2005536518A (ja) | 2002-07-19 | 2005-12-02 | ファルマシア コーポレイション | 炎症治療のための置換チオフェンカルボキサミド化合物 |
| EP1650202A4 (en) * | 2003-07-31 | 2007-04-04 | Taisho Pharmaceutical Co Ltd | 4.5-dihydronaphtho [1,2-B] thiophene |
| WO2006080406A1 (ja) * | 2005-01-28 | 2006-08-03 | Taisho Pharmaceutical Co., Ltd. | 三環性化合物 |
| WO2006080439A1 (ja) * | 2005-01-28 | 2006-08-03 | Taisho Pharmaceutical Co., Ltd. | 三環性化合物 |
| RU2506267C2 (ru) * | 2008-03-31 | 2014-02-10 | Дженентек, Инк. | Бензопирановые и бензоксепиновые ингибиторы рi3k и их применение |
| AU2012262748B2 (en) * | 2011-05-27 | 2017-03-02 | Lexicon Pharmaceuticals, Inc. | 4H-thieno[3,2-c]chromene-based inhibitors of Notum Pectinacetylesterase and methods of their use |
-
2012
- 2012-05-23 AU AU2012262748A patent/AU2012262748B2/en not_active Ceased
- 2012-05-23 CN CN201280025844.0A patent/CN103649072A/zh active Pending
- 2012-05-23 WO PCT/US2012/039087 patent/WO2012166458A1/en not_active Ceased
- 2012-05-23 DK DK12725227.8T patent/DK2714675T3/en active
- 2012-05-23 HU HUE12725227A patent/HUE043221T2/hu unknown
- 2012-05-23 EP EP12725227.8A patent/EP2714675B1/en active Active
- 2012-05-23 PL PL12725227T patent/PL2714675T3/pl unknown
- 2012-05-23 JP JP2014512959A patent/JP6166718B2/ja not_active Expired - Fee Related
- 2012-05-23 PT PT12725227T patent/PT2714675T/pt unknown
- 2012-05-23 ES ES12725227T patent/ES2715832T3/es active Active
- 2012-05-23 US US13/478,529 patent/US20120302562A1/en not_active Abandoned
- 2012-05-23 CA CA2837084A patent/CA2837084C/en active Active
-
2014
- 2014-05-21 US US14/284,106 patent/US9624238B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP2714675B1 (en) | 2019-01-02 |
| EP2714675A1 (en) | 2014-04-09 |
| ES2715832T3 (es) | 2019-06-06 |
| PT2714675T (pt) | 2019-04-12 |
| US20120302562A1 (en) | 2012-11-29 |
| US9624238B2 (en) | 2017-04-18 |
| US20140256784A1 (en) | 2014-09-11 |
| WO2012166458A1 (en) | 2012-12-06 |
| CN103649072A (zh) | 2014-03-19 |
| AU2012262748A1 (en) | 2013-11-28 |
| PL2714675T3 (pl) | 2019-07-31 |
| CA2837084A1 (en) | 2012-12-06 |
| JP6166718B2 (ja) | 2017-07-19 |
| HUE043221T2 (hu) | 2019-08-28 |
| AU2012262748B2 (en) | 2017-03-02 |
| JP2014517848A (ja) | 2014-07-24 |
| DK2714675T3 (en) | 2019-04-15 |
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| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20170512 |