TW202330530A - 咪唑并嗒𠯤il-17抑制劑化合物(二) - Google Patents
咪唑并嗒𠯤il-17抑制劑化合物(二) Download PDFInfo
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- TW202330530A TW202330530A TW111136301A TW111136301A TW202330530A TW 202330530 A TW202330530 A TW 202330530A TW 111136301 A TW111136301 A TW 111136301A TW 111136301 A TW111136301 A TW 111136301A TW 202330530 A TW202330530 A TW 202330530A
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- Prior art keywords
- alkyl
- cycloalkyl
- pharmaceutically acceptable
- acceptable salt
- compound
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 640
- 239000003112 inhibitor Substances 0.000 title description 10
- MJQSRSOTRPMVKB-UHFFFAOYSA-N 5h-imidazo[4,5-c]pyridazine Chemical compound C1=NNC2=NC=NC2=C1 MJQSRSOTRPMVKB-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 386
- 102000013691 Interleukin-17 Human genes 0.000 claims abstract description 150
- 108050003558 Interleukin-17 Proteins 0.000 claims abstract description 150
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 150
- 201000010099 disease Diseases 0.000 claims abstract description 87
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 81
- 238000000034 method Methods 0.000 claims abstract description 78
- 230000001404 mediated effect Effects 0.000 claims abstract description 70
- 208000035475 disorder Diseases 0.000 claims abstract description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 464
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 337
- -1 2 -cyclopropyl Chemical group 0.000 claims description 234
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 172
- 125000001153 fluoro group Chemical group F* 0.000 claims description 167
- 230000002757 inflammatory effect Effects 0.000 claims description 72
- 125000004432 carbon atom Chemical group C* 0.000 claims description 65
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 62
- 229910052731 fluorine Inorganic materials 0.000 claims description 59
- 239000011737 fluorine Substances 0.000 claims description 53
- 125000005843 halogen group Chemical group 0.000 claims description 35
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 26
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- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 25
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- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 21
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 20
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- 201000008937 atopic dermatitis Diseases 0.000 claims description 18
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- 206010046851 Uveitis Diseases 0.000 claims description 17
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 17
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- 125000003003 spiro group Chemical group 0.000 claims description 8
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- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
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- 125000005842 heteroatom Chemical group 0.000 claims description 3
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- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 1
- 230000000414 obstructive effect Effects 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 228
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- 239000000203 mixture Substances 0.000 description 119
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 69
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 49
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- 230000002829 reductive effect Effects 0.000 description 43
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- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 41
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 39
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- 238000003786 synthesis reaction Methods 0.000 description 32
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
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- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical group [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
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- 239000012258 stirred mixture Substances 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
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- 210000002437 synoviocyte Anatomy 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- CESUXLKAADQNTB-UHFFFAOYSA-N tert-butanesulfinamide Chemical compound CC(C)(C)S(N)=O CESUXLKAADQNTB-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- MYARHZGZFPTKKA-UHFFFAOYSA-N tributyl(propan-2-yloxymethyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)COC(C)C MYARHZGZFPTKKA-UHFFFAOYSA-N 0.000 description 1
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
- WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- HJOAXCLZLHDZDX-UHFFFAOYSA-N tris(1,2,2-trifluoroethenyl) borate Chemical compound FC(F)=C(F)OB(OC(F)=C(F)F)OC(F)=C(F)F HJOAXCLZLHDZDX-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000004614 tumor growth Effects 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
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 238000009423 ventilation 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
- 238000006886 vinylation reaction Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000007482 whole exome sequencing Methods 0.000 description 1
- 229910052725 zinc Chemical group 0.000 description 1
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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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163248566P | 2021-09-27 | 2021-09-27 | |
| US63/248,566 | 2021-09-27 | ||
| US202163273422P | 2021-10-29 | 2021-10-29 | |
| US63/273,422 | 2021-10-29 | ||
| US202263367546P | 2022-07-01 | 2022-07-01 | |
| US63/367,546 | 2022-07-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202330530A true TW202330530A (zh) | 2023-08-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111136301A TW202330530A (zh) | 2021-09-27 | 2022-09-26 | 咪唑并嗒𠯤il-17抑制劑化合物(二) |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US12173007B2 (https=) |
| EP (1) | EP4408847A1 (https=) |
| JP (1) | JP2024536869A (https=) |
| KR (1) | KR20240082369A (https=) |
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| CA (1) | CA3233408A1 (https=) |
| CL (1) | CL2024000867A1 (https=) |
| CO (1) | CO2024003723A2 (https=) |
| DO (1) | DOP2024000051A (https=) |
| IL (1) | IL311751A (https=) |
| JO (1) | JOP20240059A1 (https=) |
| MX (1) | MX2024003772A (https=) |
| PE (1) | PE20240935A1 (https=) |
| TW (1) | TW202330530A (https=) |
| UY (1) | UY39958A (https=) |
| WO (1) | WO2023049887A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2024536869A (ja) | 2021-09-27 | 2024-10-08 | ヤンセン ファーマシューティカ エヌ.ベー. | イミダゾピリダジンil-17阻害剤化合物 |
| AU2022375634A1 (en) | 2021-10-25 | 2024-06-06 | Terns Pharmaceuticals, Inc. | Compounds as glp-1r agonists |
| TW202430165A (zh) | 2022-12-02 | 2024-08-01 | 丹麥商理奧藥品公司 | Il-17之小分子調節劑 |
| WO2024163365A1 (en) * | 2023-01-30 | 2024-08-08 | Dice Alpha, Inc. | Benzimidazole and aza-benzimidazole based il-17a modulators and uses thereof |
| CN121311483A (zh) * | 2023-03-28 | 2026-01-09 | 詹森药业有限公司 | 含内酰胺的咪唑并哒嗪il-17抑制剂化合物 |
| US20240398794A1 (en) | 2023-04-07 | 2024-12-05 | Terns Pharmaceuticals, Inc. | COMBINATIONS OF GLP-1R AND THRß AGONISTS AND METHODS OF USE THEREOF |
| KR20250168657A (ko) * | 2023-04-11 | 2025-12-02 | 다이스 알파, 인크. | 치환된 6-이미다조피리다진 il-17a 조정제 및 그의 용도 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI752400B (zh) * | 2019-01-07 | 2022-01-11 | 美商美國禮來大藥廠 | Il-17a抑制劑 |
| GB201909190D0 (en) | 2019-06-26 | 2019-08-07 | Ucb Biopharma Sprl | Therapeutic agents |
| KR20230019507A (ko) | 2020-04-30 | 2023-02-08 | 얀센 파마슈티카 엔.브이. | Il-17의 조절제로서의 이미다조피리다진 |
| WO2023025783A1 (en) | 2021-08-23 | 2023-03-02 | Leo Pharma A/S | Small molecule modulators of il-17 |
| JP2024536869A (ja) | 2021-09-27 | 2024-10-08 | ヤンセン ファーマシューティカ エヌ.ベー. | イミダゾピリダジンil-17阻害剤化合物 |
| CN116143777A (zh) | 2021-11-04 | 2023-05-23 | 四川海思科制药有限公司 | 一种可抑制il-17a的杂环化合物及其用途 |
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2022
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- 2022-09-26 KR KR1020247013352A patent/KR20240082369A/ko active Pending
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Also Published As
| Publication number | Publication date |
|---|---|
| JP2024536869A (ja) | 2024-10-08 |
| WO2023049887A1 (en) | 2023-03-30 |
| JOP20240059A1 (ar) | 2024-03-26 |
| KR20240082369A (ko) | 2024-06-10 |
| US20230143050A1 (en) | 2023-05-11 |
| MX2024003772A (es) | 2024-06-19 |
| CO2024003723A2 (es) | 2024-04-18 |
| EP4408847A1 (en) | 2024-08-07 |
| US20250109137A1 (en) | 2025-04-03 |
| UY39958A (es) | 2023-04-28 |
| DOP2024000051A (es) | 2024-11-15 |
| US12173007B2 (en) | 2024-12-24 |
| PE20240935A1 (es) | 2024-04-30 |
| CA3233408A1 (en) | 2023-03-30 |
| IL311751A (en) | 2024-05-01 |
| CL2024000867A1 (es) | 2024-09-23 |
| AU2022349687A1 (en) | 2024-05-16 |
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