KR20180134395A - Nlrp3 조정제 - Google Patents
Nlrp3 조정제 Download PDFInfo
- Publication number
- KR20180134395A KR20180134395A KR1020187032949A KR20187032949A KR20180134395A KR 20180134395 A KR20180134395 A KR 20180134395A KR 1020187032949 A KR1020187032949 A KR 1020187032949A KR 20187032949 A KR20187032949 A KR 20187032949A KR 20180134395 A KR20180134395 A KR 20180134395A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- optionally substituted
- compound
- ring atoms
- group
- 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.)
- Ceased
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- 108010001946 Pyrin Domain-Containing 3 Protein NLR Family Proteins 0.000 title claims abstract description 46
- 102000000874 Pyrin Domain-Containing 3 Protein NLR Family Human genes 0.000 title abstract description 42
- 150000001875 compounds Chemical class 0.000 claims abstract description 207
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 49
- 201000011510 cancer Diseases 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 230000000694 effects Effects 0.000 claims abstract description 15
- 230000036961 partial effect Effects 0.000 claims abstract description 7
- 125000006413 ring segment Chemical group 0.000 claims description 300
- 125000000217 alkyl group Chemical group 0.000 claims description 229
- 125000002947 alkylene group Chemical group 0.000 claims description 199
- 229910052757 nitrogen Inorganic materials 0.000 claims description 195
- 229910052739 hydrogen Inorganic materials 0.000 claims description 121
- 125000001072 heteroaryl group Chemical group 0.000 claims description 117
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 108
- 229910052760 oxygen Inorganic materials 0.000 claims description 108
- 238000000034 method Methods 0.000 claims description 106
- 229910052717 sulfur Inorganic materials 0.000 claims description 99
- -1 phosphorus compound Chemical class 0.000 claims description 95
- 239000001257 hydrogen Substances 0.000 claims description 79
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 77
- 125000003545 alkoxy group Chemical group 0.000 claims description 74
- 125000003118 aryl group Chemical group 0.000 claims description 70
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 68
- 239000001301 oxygen Substances 0.000 claims description 62
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 53
- 229910052799 carbon Inorganic materials 0.000 claims description 51
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 50
- 239000011593 sulfur Substances 0.000 claims description 50
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 49
- 125000005843 halogen group Chemical group 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 41
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims description 37
- 125000002883 imidazolyl group Chemical group 0.000 claims description 37
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 33
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000001425 triazolyl group Chemical group 0.000 claims description 33
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 18
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 17
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- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 6
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 5
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 5
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- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
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- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 5
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- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 5
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- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 5
- 229960004528 vincristine Drugs 0.000 claims description 5
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- 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
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- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—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 oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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| US62/460,519 | 2017-02-17 | ||
| PCT/US2017/028384 WO2017184746A1 (en) | 2016-04-19 | 2017-04-19 | Nlrp3 modulators |
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| KR20210114982A (ko) * | 2019-01-14 | 2021-09-24 | 인네이트 튜머 이뮤니티, 인코포레이티드 | 암의 치료에 사용하기 위한 헤테로시클릭 nlrp3 조정제 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210114982A (ko) * | 2019-01-14 | 2021-09-24 | 인네이트 튜머 이뮤니티, 인코포레이티드 | 암의 치료에 사용하기 위한 헤테로시클릭 nlrp3 조정제 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2017184746A1 (en) | 2017-10-26 |
| CN109071535A (zh) | 2018-12-21 |
| CA3021349A1 (en) | 2017-10-26 |
| US10556903B2 (en) | 2020-02-11 |
| AU2017252640A1 (en) | 2018-12-06 |
| JP7104633B2 (ja) | 2022-07-21 |
| EP3445761A1 (en) | 2019-02-27 |
| US20200157097A1 (en) | 2020-05-21 |
| US20190127367A1 (en) | 2019-05-02 |
| JP7104633B6 (ja) | 2023-12-22 |
| CN109071535B (zh) | 2021-10-08 |
| JP2019513809A (ja) | 2019-05-30 |
| MX2018012249A (es) | 2019-02-07 |
| US11072612B2 (en) | 2021-07-27 |
| IL262303A (en) | 2018-12-31 |
| SG11201809082WA (en) | 2018-11-29 |
| BR112018071347A2 (pt) | 2019-02-05 |
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