IL303795A

IL303795A - Chemical compounds useful for inhibition of NAV1.8 voltage-gated sodium channels and treatment of NAV1.8-mediated diseases

Chemical compounds useful for inhibition of NAV1.8 voltage-gated sodium channels and treatment of NAV1.8-mediated diseases

Info

Publication number: IL303795A
Authority: IL; Israel
Prior art keywords: pain; compound; pharmaceutically acceptable; acceptable salt; alkyl
Prior art date: 2020-12-18

Application number

IL303795A

Other languages

English (en)

Hebrew (he)

Original Assignee

Glaxosmithkline Ip Dev Ltd

Priority date

2020-12-18

Filing date

2021-12-16

Publication date

2023-08-01

2021-12-16 Application filed by Glaxosmithkline Ip Dev Ltd filed Critical Glaxosmithkline Ip Dev Ltd

2023-08-01 Publication of IL303795A publication Critical patent/IL303795A/en

Links

150000001875 compounds Chemical class 0.000 title claims description 316
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 112
201000010099 disease Diseases 0.000 title claims description 59
230000001404 mediated effect Effects 0.000 title claims description 11
230000002401 inhibitory effect Effects 0.000 title description 9
108010056565 NAV1.8 Voltage-Gated Sodium Channel Proteins 0.000 title description 2
102000004194 NAV1.8 Voltage-Gated Sodium Channel Human genes 0.000 title description 2
208000002193 Pain Diseases 0.000 claims description 226
230000036407 pain Effects 0.000 claims description 198
150000003839 salts Chemical class 0.000 claims description 146
239000008194 pharmaceutical composition Substances 0.000 claims description 83
238000000034 method Methods 0.000 claims description 75
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238000011282 treatment Methods 0.000 claims description 57
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208000035475 disorder Diseases 0.000 claims description 53
229910052739 hydrogen Inorganic materials 0.000 claims description 50
239000001257 hydrogen Substances 0.000 claims description 50
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238000001990 intravenous administration Methods 0.000 claims description 17
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
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125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 14
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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
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VWTOFRNSHHUBPP-UHFFFAOYSA-N [3-[1-(4-fluoro-2-methylphenyl)-4-oxo-6-(trifluoromethyl)-2H-quinazolin-3-yl]-2-methyl-6-oxopyridin-1-yl]methyl dihydrogen phosphate Chemical compound CC(C=C(C=C1)F)=C1N(CN1C(C=C2)=C(C)N(COP(O)(O)=O)C2=O)C2=CC=C(C(F)(F)F)C=C2C1=O VWTOFRNSHHUBPP-UHFFFAOYSA-N 0.000 claims description 3
SQOAVOGMZCUHHE-UHFFFAOYSA-N [3-[6-chloro-1-(4-fluoro-2-methylphenyl)-4-oxo-2H-quinazolin-3-yl]-2-methyl-6-oxopyridin-1-yl]methyl dihydrogen phosphate Chemical compound CC(C=C(C=C1)F)=C1N(CN(C(C=C1)=C(C)N(COP(O)(O)=O)C1=O)C(C1=C2)=O)C1=CC=C2Cl SQOAVOGMZCUHHE-UHFFFAOYSA-N 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
229910052705 radium Inorganic materials 0.000 claims description 3
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JVADFCVBYOYMRX-UHFFFAOYSA-N [2-methyl-3-[1-[2-methyl-4-(trifluoromethoxy)phenyl]-4-oxo-6-(trifluoromethyl)-2H-pyrido[2,3-d]pyrimidin-3-yl]-6-oxopyridin-1-yl]methyl dihydrogen phosphate Chemical compound CC(C=C(C=C1)OC(F)(F)F)=C1N(CN1C(C=C2)=C(C)N(COP(O)(O)=O)C2=O)C(N=CC(C(F)(F)F)=C2)=C2C1=O JVADFCVBYOYMRX-UHFFFAOYSA-N 0.000 claims description 2
YOEPKAJXVHOHLL-UHFFFAOYSA-N [3-[1-(4-fluoro-2-methylphenyl)-4-oxo-7-(trifluoromethyl)-2H-quinazolin-3-yl]-2-methyl-6-oxopyridin-1-yl]methyl dihydrogen phosphate Chemical compound CC(C=C(C=C1)F)=C1N(CN1C(C=C2)=C(C)N(COP(O)(O)=O)C2=O)C2=CC(C(F)(F)F)=CC=C2C1=O YOEPKAJXVHOHLL-UHFFFAOYSA-N 0.000 claims description 2
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OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
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