TW202320797A

TW202320797A - 使用ｖｐｓ３４抑制劑之組合療法

使用ｖｐｓ３４抑制劑之組合療法 Download PDF

Info

Publication number: TW202320797A
Authority: TW; Taiwan
Prior art keywords: pyridin; alkyl; group; trifluoromethyl; methyl
Prior art date: 2021-08-13

Application number

TW111130481A

Other languages

English (en)

Chinese (zh)

Inventor

雅絲敏于

馬丁安德森

丹尼爾Ｌ佛林

瑪杜米塔博格丹

Original Assignee

美商迪賽孚爾製藥有限公司

Priority date

2021-08-13

Filing date

2022-08-12

Publication date

2023-06-01

2022-08-12 Application filed by 美商迪賽孚爾製藥有限公司 filed Critical 美商迪賽孚爾製藥有限公司

2023-06-01 Publication of TW202320797A publication Critical patent/TW202320797A/zh

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239000003112 inhibitor Substances 0.000 title abstract description 23
238000002648 combination therapy Methods 0.000 title description 9
101100190557 Caenorhabditis elegans vps-34 gene Proteins 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 92
229940044665 STING agonist Drugs 0.000 claims abstract description 81
206010028980 Neoplasm Diseases 0.000 claims abstract description 71
201000011510 cancer Diseases 0.000 claims abstract description 45
239000003814 drug Substances 0.000 claims abstract description 26
229940124597 therapeutic agent Drugs 0.000 claims abstract description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 289
-1 Azol-3-yl Chemical group 0.000 claims description 261
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 212
150000001875 compounds Chemical class 0.000 claims description 189
229910052736 halogen Inorganic materials 0.000 claims description 179
229910052739 hydrogen Inorganic materials 0.000 claims description 177
150000002367 halogens Chemical class 0.000 claims description 148
150000003839 salts Chemical class 0.000 claims description 125
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 122
125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 121
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 119
GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 110
241000009298 Trigla lyra Species 0.000 claims description 106
230000014509 gene expression Effects 0.000 claims description 103
229910052799 carbon Inorganic materials 0.000 claims description 87
239000000203 mixture Substances 0.000 claims description 87
125000001072 heteroaryl group Chemical group 0.000 claims description 85
125000001424 substituent group Chemical group 0.000 claims description 80
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 79
125000000623 heterocyclic group Chemical group 0.000 claims description 78
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 72
125000005843 halogen group Chemical group 0.000 claims description 71
230000037361 pathway Effects 0.000 claims description 71
102100032367 C-C motif chemokine 5 Human genes 0.000 claims description 68
102100025248 C-X-C motif chemokine 10 Human genes 0.000 claims description 65
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 claims description 62
101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 claims description 62
230000001965 increasing effect Effects 0.000 claims description 61
125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 58
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 56
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 48
125000003118 aryl group Chemical group 0.000 claims description 44
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 42
229910000063 azene Inorganic materials 0.000 claims description 41
239000002975 chemoattractant Substances 0.000 claims description 41
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 40
102000019034 Chemokines Human genes 0.000 claims description 35
108010012236 Chemokines Proteins 0.000 claims description 35
239000000460 chlorine Chemical group 0.000 claims description 33
229910052801 chlorine Inorganic materials 0.000 claims description 32
229910052731 fluorine Inorganic materials 0.000 claims description 31
239000011737 fluorine Substances 0.000 claims description 31
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 30
125000001153 fluoro group Chemical group F* 0.000 claims description 29
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 26
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 26
208000006265 Renal cell carcinoma Diseases 0.000 claims description 24
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 23
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 23
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 22
206010038389 Renal cancer Diseases 0.000 claims description 21
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
239000003795 chemical substances by application Substances 0.000 claims description 21
239000001301 oxygen Substances 0.000 claims description 21
229910052760 oxygen Inorganic materials 0.000 claims description 21
229940126253 ADU-S100 Drugs 0.000 claims description 20
125000000217 alkyl group Chemical group 0.000 claims description 19
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
230000010472 type I IFN response Effects 0.000 claims description 19
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 18
238000006467 substitution reaction Methods 0.000 claims description 17
208000008839 Kidney Neoplasms Diseases 0.000 claims description 15
201000010982 kidney cancer Diseases 0.000 claims description 15
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 14
239000005557 antagonist Substances 0.000 claims description 14
ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 13
125000002619 bicyclic group Chemical group 0.000 claims description 10
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
WEUPTDZSLQUHHB-UHFFFAOYSA-N 4-(2-aminopyridin-4-yl)-6-(2-chlorophenyl)-1H-pyridin-2-one Chemical compound NC1=NC=CC(=C1)C1=CC(NC(=C1)C1=C(C=CC=C1)Cl)=O WEUPTDZSLQUHHB-UHFFFAOYSA-N 0.000 claims description 9
LRUDZBBEMDATJL-UHFFFAOYSA-N 4-(2-aminopyridin-4-yl)-6-pyridin-3-yl-1H-pyridin-2-one Chemical compound NC1=NC=CC(=C1)C1=CC(NC(=C1)C=1C=NC=CC=1)=O LRUDZBBEMDATJL-UHFFFAOYSA-N 0.000 claims description 9
KKVYWNGJTJAGDA-UHFFFAOYSA-N 4-(2-anilinopyrimidin-4-yl)-6-[2-(trifluoromethyl)piperidin-1-yl]-1H-pyridin-2-one Chemical compound N(C1=CC=CC=C1)C1=NC=CC(=N1)C1=CC(NC(=C1)N1C(CCCC1)C(F)(F)F)=O KKVYWNGJTJAGDA-UHFFFAOYSA-N 0.000 claims description 9
WVOMBCDICRIDRP-UHFFFAOYSA-N 4-(2-anilinopyrimidin-4-yl)-6-pyridin-3-yl-1H-pyridin-2-one Chemical compound N(C1=CC=CC=C1)C1=NC=CC(=N1)C1=CC(NC(=C1)C=1C=NC=CC=1)=O WVOMBCDICRIDRP-UHFFFAOYSA-N 0.000 claims description 9
XPYHHTPXESGWCC-UHFFFAOYSA-N 4-(2-anilinopyrimidin-4-yl)-6-pyridin-4-yl-1H-pyridin-2-one Chemical compound N(C1=CC=CC=C1)C1=NC=CC(=N1)C1=CC(NC(=C1)C1=CC=NC=C1)=O XPYHHTPXESGWCC-UHFFFAOYSA-N 0.000 claims description 9
KHHNKBNKRAKFFF-UHFFFAOYSA-N 4-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]-6-[2-(trifluoromethyl)phenyl]-1H-pyridin-2-one Chemical compound CC1=NC=CC(=N1)NC1=NC=CC(=C1)C1=CC(NC(=C1)C1=C(C=CC=C1)C(F)(F)F)=O KHHNKBNKRAKFFF-UHFFFAOYSA-N 0.000 claims description 9
PEWRKYRCKSBJJX-UHFFFAOYSA-N 4-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]-6-[2-(trifluoromethyl)piperidin-1-yl]-1H-pyridin-2-one Chemical compound CC1=NC=CC(=N1)NC1=NC=CC(=C1)C1=CC(NC(=C1)N1C(CCCC1)C(F)(F)F)=O PEWRKYRCKSBJJX-UHFFFAOYSA-N 0.000 claims description 9
PCCBNYMSCHHQPR-UHFFFAOYSA-N 6-(4-methylpyridin-3-yl)-4-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]-1H-pyridin-2-one Chemical compound CC1=C(C=NC=C1)C1=CC(=CC(N1)=O)C1=CC(=NC=C1)NC1=NC(=NC=C1)C PCCBNYMSCHHQPR-UHFFFAOYSA-N 0.000 claims description 9
JTUBLRKWQWLDGI-UHFFFAOYSA-N N-[4-[2-(4-methylpyridin-3-yl)-6-oxo-1H-pyridin-4-yl]pyridin-2-yl]acetamide Chemical compound CC1=C(C=NC=C1)C=1NC(C=C(C=1)C1=CC(=NC=C1)NC(C)=O)=O JTUBLRKWQWLDGI-UHFFFAOYSA-N 0.000 claims description 9
WYKJXFMXVUDREO-UHFFFAOYSA-N N-[4-[2-oxo-6-[2-(trifluoromethyl)phenyl]-1H-pyridin-4-yl]pyridin-2-yl]acetamide Chemical compound O=C1NC(=CC(=C1)C1=CC(=NC=C1)NC(C)=O)C1=C(C=CC=C1)C(F)(F)F WYKJXFMXVUDREO-UHFFFAOYSA-N 0.000 claims description 9
SXTBJUQDFNIUBC-UHFFFAOYSA-N N-[4-[2-oxo-6-[2-(trifluoromethyl)piperidin-1-yl]-1H-pyridin-4-yl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound O=C1NC(=CC(=C1)C1=CC(=NC=C1)NC(=O)C1CC1)N1C(CCCC1)C(F)(F)F SXTBJUQDFNIUBC-UHFFFAOYSA-N 0.000 claims description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
ULRZATBBRNFUII-UHFFFAOYSA-N N-[4-[2-(2-chlorophenyl)-6-oxo-1H-pyridin-4-yl]pyridin-2-yl]-2-methoxyacetamide Chemical compound ClC1=C(C=CC=C1)C=1NC(C=C(C=1)C1=CC(=NC=C1)NC(COC)=O)=O ULRZATBBRNFUII-UHFFFAOYSA-N 0.000 claims description 8
WSZRNKMWOZHSEK-UHFFFAOYSA-N N-[4-[2-oxo-6-[2-(trifluoromethyl)piperidin-1-yl]-1H-pyridin-4-yl]pyridin-2-yl]acetamide Chemical compound O=C1NC(=CC(=C1)C1=CC(=NC=C1)NC(C)=O)N1C(CCCC1)C(F)(F)F WSZRNKMWOZHSEK-UHFFFAOYSA-N 0.000 claims description 8
150000001335 aliphatic alkanes Chemical class 0.000 claims description 8
208000014829 head and neck neoplasm Diseases 0.000 claims description 8
150000003254 radicals Chemical class 0.000 claims description 8
ULEDSARUYZXCMY-UHFFFAOYSA-N 6-(2-chlorophenyl)-4-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]-1H-pyridin-2-one Chemical compound ClC1=C(C=CC=C1)C1=CC(=CC(N1)=O)C1=CC(=NC=C1)NC1=NC(=NC=C1)C ULEDSARUYZXCMY-UHFFFAOYSA-N 0.000 claims description 7
201000001441 melanoma Diseases 0.000 claims description 7
125000003386 piperidinyl group Chemical group 0.000 claims description 7
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
QVXZGMUKOWYSOX-UHFFFAOYSA-N 4-(1H-pyrazolo[3,4-b]pyridin-4-yl)-6-[2-(trifluoromethyl)piperidin-1-yl]-1H-pyridin-2-one Chemical compound N1N=CC=2C1=NC=CC=2C1=CC(NC(=C1)N1C(CCCC1)C(F)(F)F)=O QVXZGMUKOWYSOX-UHFFFAOYSA-N 0.000 claims description 6
DOJFVPVHXQICAN-UHFFFAOYSA-N 4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-6-[2-(trifluoromethyl)piperidin-1-yl]-1H-pyridin-2-one Chemical compound N1C=CC=2C1=NC=CC=2C1=CC(NC(=C1)N1C(CCCC1)C(F)(F)F)=O DOJFVPVHXQICAN-UHFFFAOYSA-N 0.000 claims description 6
IBNJRAAEJIHRLO-UHFFFAOYSA-N 4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-6-[2-(trifluoromethyl)piperidin-1-yl]-1H-pyridin-2-one Chemical compound CC1=CC=2C(=NC=CC=2C2=CC(NC(=C2)N2C(CCCC2)C(F)(F)F)=O)N1 IBNJRAAEJIHRLO-UHFFFAOYSA-N 0.000 claims description 6
HPLXYLKQWASIQD-UHFFFAOYSA-N 4-[2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl]-6-[2-(trifluoromethyl)pyridin-3-yl]-1H-pyridin-2-one Chemical compound CC1=NC=CC(=N1)NC1=NC=CC(=C1)C1=CC(NC(=C1)C=1C(=NC=CC=1)C(F)(F)F)=O HPLXYLKQWASIQD-UHFFFAOYSA-N 0.000 claims description 6
PUNDGYRIKMMQHI-UHFFFAOYSA-N 6-(2-chlorophenyl)-4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyridin-2-one Chemical compound ClC1=C(C=CC=C1)C1=CC(=CC(N1)=O)C1=C2C(=NC=C1)NC(=C2)C PUNDGYRIKMMQHI-UHFFFAOYSA-N 0.000 claims description 6
KUHXRVPOFWEIIL-UHFFFAOYSA-N 6-(2-chlorophenyl)-4-(2-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyridin-2-one Chemical compound ClC1=C(C=CC=C1)C1=CC(=CC(N1)=O)C1=C2C(=NC=C1)NC(=C2)C=1C=NC=CC=1 KUHXRVPOFWEIIL-UHFFFAOYSA-N 0.000 claims description 6
LRTZISIKPSKAIP-UHFFFAOYSA-N 6-[2-(trifluoromethyl)piperidin-1-yl]-4-[2-[5-(trifluoromethyl)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-pyridin-2-one Chemical compound FC(C1N(CCCC1)C1=CC(=CC(N1)=O)C1=C2C(=NC=C1)NC(=C2)C=1C=NC=C(C=1)C(F)(F)F)(F)F LRTZISIKPSKAIP-UHFFFAOYSA-N 0.000 claims description 6
SCKYJZZLWPCYAC-UHFFFAOYSA-N 6-[2-(trifluoromethyl)piperidin-1-yl]-4-[2-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1H-pyridin-2-one Chemical compound FC(C1N(CCCC1)C1=CC(=CC(N1)=O)C1=C2C(=NC=C1)NC(=C2)C=1C=NC(=CC=1)C(F)(F)F)(F)F SCKYJZZLWPCYAC-UHFFFAOYSA-N 0.000 claims description 6
WHWGYPKJDYJZPK-UHFFFAOYSA-N N-[4-[2-[1-ethyl-3-(trifluoromethyl)pyrazol-4-yl]-6-oxo-1H-pyridin-4-yl]pyridin-2-yl]acetamide Chemical compound C(C)N1N=C(C(=C1)C=1NC(C=C(C=1)C1=CC(=NC=C1)NC(C)=O)=O)C(F)(F)F WHWGYPKJDYJZPK-UHFFFAOYSA-N 0.000 claims description 6
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
150000001350 alkyl halides Chemical class 0.000 claims description 6
229940124530 sulfonamide Drugs 0.000 claims description 6
AINQHQYRXCJWMT-UHFFFAOYSA-N 4-(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-6-pyridin-3-yl-1H-pyridin-2-one Chemical compound CC1=CC=2C(=NC=CC=2C2=CC(NC(=C2)C=2C=NC=CC=2)=O)N1 AINQHQYRXCJWMT-UHFFFAOYSA-N 0.000 claims description 5
FMUDKKVYHUYDHN-UHFFFAOYSA-N N-[4-[2-oxo-6-[2-(trifluoromethyl)pyridin-3-yl]-1H-pyridin-4-yl]pyridin-2-yl]acetamide Chemical compound O=C1NC(=CC(=C1)C1=CC(=NC=C1)NC(C)=O)C=1C(=NC=CC=1)C(F)(F)F FMUDKKVYHUYDHN-UHFFFAOYSA-N 0.000 claims description 5
125000003282 alkyl amino group Chemical group 0.000 claims description 5
SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 4
206010005003 Bladder cancer Diseases 0.000 claims description 4
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208000026310 Breast neoplasm Diseases 0.000 claims description 4
CLGJCTXUWJLYHO-UHFFFAOYSA-N CSC1=C(Cl)C=CC2=C1N(CC(O)=O)C1=C(C=CC(=C1)C(C)(C)C)C2=O Chemical compound CSC1=C(Cl)C=CC2=C1N(CC(O)=O)C1=C(C=CC(=C1)C(C)(C)C)C2=O CLGJCTXUWJLYHO-UHFFFAOYSA-N 0.000 claims description 4
206010008342 Cervix carcinoma Diseases 0.000 claims description 4
206010009944 Colon cancer Diseases 0.000 claims description 4
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208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
208000002495 Uterine Neoplasms Diseases 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
239000000611 antibody drug conjugate Substances 0.000 claims description 4
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210000000988 bone and bone Anatomy 0.000 claims description 4
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125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
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ONHSGOPTCOTAQD-UHFFFAOYSA-N 1,1-dimethyl-3-[4-[2-oxo-6-[2-(trifluoromethyl)phenyl]-1H-pyridin-4-yl]pyridin-2-yl]urea Chemical compound CN(C(=O)NC1=NC=CC(=C1)C1=CC(NC(=C1)C1=C(C=CC=C1)C(F)(F)F)=O)C ONHSGOPTCOTAQD-UHFFFAOYSA-N 0.000 claims description 3
KDDZUAZEHFIWMN-UHFFFAOYSA-N 4-(1H-pyrazolo[3,4-b]pyridin-4-yl)-6-[2-(trifluoromethyl)phenyl]-1H-pyridin-2-one Chemical compound N1N=CC=2C1=NC=CC=2C1=CC(NC(=C1)C1=C(C=CC=C1)C(F)(F)F)=O KDDZUAZEHFIWMN-UHFFFAOYSA-N 0.000 claims description 3
UHLMTCFPIOAJRK-UHFFFAOYSA-N 4-(2-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-6-[2-(trifluoromethyl)phenyl]-1H-pyridin-2-one Chemical compound C1(CC1)C1=CC=2C(=NC=CC=2C2=CC(NC(=C2)C2=C(C=CC=C2)C(F)(F)F)=O)N1 UHLMTCFPIOAJRK-UHFFFAOYSA-N 0.000 claims description 3
QZULWMRAPVCTTC-UHFFFAOYSA-N 4-[2-[(2-methyl-1,3-thiazol-4-yl)amino]pyridin-4-yl]-6-[2-(trifluoromethyl)phenyl]-1H-pyridin-2-one Chemical compound CC=1SC=C(N=1)NC1=NC=CC(=C1)C1=CC(NC(=C1)C1=C(C=CC=C1)C(F)(F)F)=O QZULWMRAPVCTTC-UHFFFAOYSA-N 0.000 claims description 3
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