JPWO2020014246A5 - - Google Patents
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- Publication number
- JPWO2020014246A5 JPWO2020014246A5 JP2021500411A JP2021500411A JPWO2020014246A5 JP WO2020014246 A5 JPWO2020014246 A5 JP WO2020014246A5 JP 2021500411 A JP2021500411 A JP 2021500411A JP 2021500411 A JP2021500411 A JP 2021500411A JP WO2020014246 A5 JPWO2020014246 A5 JP WO2020014246A5
- Authority
- JP
- Japan
- Prior art keywords
- trifluoromethyl
- carboxamide
- phenoxy
- pyridin
- alkyl
- 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.)
- Pending
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- -1 cyano, amino Chemical group 0.000 claims description 824
- 150000001875 compounds Chemical class 0.000 claims description 296
- 125000000217 alkyl group Chemical group 0.000 claims description 252
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 170
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 167
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 153
- 239000000203 mixture Substances 0.000 claims description 124
- 229910052757 nitrogen Inorganic materials 0.000 claims description 98
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 229910052799 carbon Inorganic materials 0.000 claims description 90
- 229910052736 halogen Inorganic materials 0.000 claims description 89
- 150000002367 halogens Chemical class 0.000 claims description 88
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 86
- 201000006417 multiple sclerosis Diseases 0.000 claims description 75
- 125000003545 alkoxy group Chemical group 0.000 claims description 66
- 239000011734 sodium Substances 0.000 claims description 65
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000001072 heteroaryl group Chemical group 0.000 claims description 54
- 239000011780 sodium chloride Substances 0.000 claims description 53
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 50
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 42
- 125000004076 pyridyl group Chemical group 0.000 claims description 42
- 208000002193 Pain Diseases 0.000 claims description 41
- 125000004432 carbon atoms Chemical group C* 0.000 claims description 41
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 37
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 36
- 230000002401 inhibitory effect Effects 0.000 claims description 36
- 230000036407 pain Effects 0.000 claims description 36
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 201000010099 disease Diseases 0.000 claims description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 30
- 125000002757 morpholinyl group Chemical group 0.000 claims description 25
- 102000018674 Sodium Channels Human genes 0.000 claims description 24
- 108010052164 Sodium Channels Proteins 0.000 claims description 24
- 125000004043 oxo group Chemical group O=* 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 19
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
- 125000004104 aryloxy group Chemical group 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 17
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 16
- 125000005418 aryl aryl group Chemical group 0.000 claims description 16
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 16
- 230000014509 gene expression Effects 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 125000002971 oxazolyl group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 12
- 230000001965 increased Effects 0.000 claims description 12
- ILVXOBCQQYKLDS-UHFFFAOYSA-N Pyridine-N-oxide Chemical group [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 11
- 229940079593 drugs Drugs 0.000 claims description 11
- 239000011570 nicotinamide Substances 0.000 claims description 10
- 235000005152 nicotinamide Nutrition 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
- 208000004296 Neuralgia Diseases 0.000 claims description 9
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 8
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 6
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 6
- 201000011384 erythromelalgia Diseases 0.000 claims description 6
- 230000001105 regulatory Effects 0.000 claims description 6
- 206010065390 Inflammatory pain Diseases 0.000 claims description 5
- 206010029331 Neuropathy peripheral Diseases 0.000 claims description 5
- 229940005483 OPIOID ANALGESICS Drugs 0.000 claims description 5
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 201000001119 neuropathy Diseases 0.000 claims description 5
- 239000000014 opioid analgesic Substances 0.000 claims description 5
- 201000010874 syndrome Diseases 0.000 claims description 5
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 4
- 206010003119 Arrhythmia Diseases 0.000 claims description 4
- 206010007521 Cardiac arrhythmias Diseases 0.000 claims description 4
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 229940093912 Gynecological Sulfonamides Drugs 0.000 claims description 4
- 206010019233 Headache Diseases 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 229940079867 intestinal antiinfectives Sulfonamides Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229940005938 ophthalmologic antiinfectives Sulfonamides Drugs 0.000 claims description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N p-acetaminophenol Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 4
- 229960005489 paracetamol Drugs 0.000 claims description 4
- 230000002093 peripheral Effects 0.000 claims description 4
- 150000003456 sulfonamides Chemical group 0.000 claims description 4
- 229940026752 topical Sulfonamides Drugs 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 229940022659 Acetaminophen Drugs 0.000 claims description 3
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims description 3
- 208000009935 Visceral Pain Diseases 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 claims description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
- 206010002855 Anxiety Diseases 0.000 claims description 2
- 206010057666 Anxiety disease Diseases 0.000 claims description 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 206010003246 Arthritis Diseases 0.000 claims description 2
- 206010003658 Atrial fibrillation Diseases 0.000 claims description 2
- 206010004939 Bipolar I disease Diseases 0.000 claims description 2
- 206010004938 Bipolar disease Diseases 0.000 claims description 2
- 206010011401 Crohn's disease Diseases 0.000 claims description 2
- 208000001636 Diabetic Neuropathy Diseases 0.000 claims description 2
- 206010012680 Diabetic neuropathy Diseases 0.000 claims description 2
- 208000010118 Dystonia Diseases 0.000 claims description 2
- 208000001640 Fibromyalgia Diseases 0.000 claims description 2
- 208000007514 Herpes Zoster Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 206010020844 Hyperthermia malignant Diseases 0.000 claims description 2
- 208000003532 Hypothyroidism Diseases 0.000 claims description 2
- 206010022114 Injury Diseases 0.000 claims description 2
- 102100017700 LGI1 Human genes 0.000 claims description 2
- 101700058968 LGI1 Proteins 0.000 claims description 2
- 208000007914 Labor Pain Diseases 0.000 claims description 2
- 206010059204 Labour pain Diseases 0.000 claims description 2
- 206010052313 Liddle's syndrome Diseases 0.000 claims description 2
- 206010027599 Migraine Diseases 0.000 claims description 2
- 208000008085 Migraine Disorders Diseases 0.000 claims description 2
- 206010028372 Muscular weakness Diseases 0.000 claims description 2
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 claims description 2
- 206010029279 Neurogenic bladder Diseases 0.000 claims description 2
- 208000001293 Peripheral Nervous System Disease Diseases 0.000 claims description 2
- 206010034606 Peripheral neuropathy Diseases 0.000 claims description 2
- 206010056238 Phantom pain Diseases 0.000 claims description 2
- 208000004550 Postoperative Pain Diseases 0.000 claims description 2
- 208000000399 Procedural Pain Diseases 0.000 claims description 2
- 208000003251 Pruritus Diseases 0.000 claims description 2
- 206010037113 Pseudoaldosteronism Diseases 0.000 claims description 2
- 206010039073 Rheumatoid arthritis Diseases 0.000 claims description 2
- FDDDEECHVMSUSB-UHFFFAOYSA-N Sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 2
- 206010043269 Tension headache Diseases 0.000 claims description 2
- 208000008548 Tension-Type Headache Diseases 0.000 claims description 2
- 206010043994 Tonic convulsion Diseases 0.000 claims description 2
- 208000004371 Toothache Diseases 0.000 claims description 2
- 231100000765 Toxin Toxicity 0.000 claims description 2
- 210000003901 Trigeminal Nerve Anatomy 0.000 claims description 2
- 208000003663 Ventricular Fibrillation Diseases 0.000 claims description 2
- 229910000272 alkali metal oxide Inorganic materials 0.000 claims description 2
- 201000005794 allergic hypersensitivity disease Diseases 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 201000001320 atherosclerosis Diseases 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 201000003883 cystic fibrosis Diseases 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 230000009610 hypersensitivity Effects 0.000 claims description 2
- 230000002989 hypothyroidism Effects 0.000 claims description 2
- 230000000302 ischemic Effects 0.000 claims description 2
- 201000010901 lateral sclerosis Diseases 0.000 claims description 2
- 201000007004 malignant hyperthermia Diseases 0.000 claims description 2
- 230000036473 myasthenia Effects 0.000 claims description 2
- 230000004112 neuroprotection Effects 0.000 claims description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 2
- 230000001314 paroxysmal Effects 0.000 claims description 2
- 230000002085 persistent Effects 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 201000009890 sinusitis Diseases 0.000 claims description 2
- 229960001663 sulfanilamide Drugs 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 239000003053 toxin Substances 0.000 claims description 2
- 230000000472 traumatic Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 7
- 206010009887 Colitis Diseases 0.000 claims 1
- 210000003414 Extremities Anatomy 0.000 claims 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N Hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 1
- 101710006116 IL31RA Proteins 0.000 claims 1
- 210000003205 Muscles Anatomy 0.000 claims 1
- 208000005010 Paroxysmal Extreme Pain Disorder Diseases 0.000 claims 1
- 206010011302 Peripheral nerve injury Diseases 0.000 claims 1
- 206010039020 Rhabdomyolysis Diseases 0.000 claims 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 1
- 230000000541 pulsatile Effects 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 93
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 88
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 238000003786 synthesis reaction Methods 0.000 description 63
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- 239000000243 solution Substances 0.000 description 60
- 238000005160 1H NMR spectroscopy Methods 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 38
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- 239000002904 solvent Substances 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 239000002244 precipitate Substances 0.000 description 33
- 238000001914 filtration Methods 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
- 239000003795 chemical substances by application Substances 0.000 description 24
- FJDQFPXHSGXQBY-UHFFFAOYSA-L Caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 22
- 125000004435 hydrogen atoms Chemical class [H]* 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
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- UQYZFNUUOSSNKT-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium;hexafluorophosphate Chemical compound F[P-](F)(F)(F)(F)F.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 UQYZFNUUOSSNKT-UHFFFAOYSA-N 0.000 description 19
- 239000002253 acid Substances 0.000 description 19
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- 125000004404 heteroalkyl group Chemical group 0.000 description 17
- 125000005842 heteroatoms Chemical group 0.000 description 17
- 229910052708 sodium Inorganic materials 0.000 description 17
- MBNPJRQKQLLRIS-UHFFFAOYSA-N 3-methylsulfonylaniline Chemical compound CS(=O)(=O)C1=CC=CC(N)=C1 MBNPJRQKQLLRIS-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 238000001816 cooling Methods 0.000 description 15
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- 125000002947 alkylene group Chemical group 0.000 description 14
- 238000004166 bioassay Methods 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- IMNFDUFMRHMDMM-UHFFFAOYSA-N n-heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
- OULGLTLTWBZBLO-UHFFFAOYSA-N 4-fluoro-2-methoxyphenol Chemical compound COC1=CC(F)=CC=C1O OULGLTLTWBZBLO-UHFFFAOYSA-N 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 125000004429 atoms Chemical group 0.000 description 13
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
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- 125000000304 alkynyl group Chemical group 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
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- 238000006243 chemical reaction Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 6
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WO2020176763A1 (en) | 2019-02-27 | 2020-09-03 | Vertex Pharmaceuticals Incorporated | Dosage form comprising prodrug of na 1.8 sodium channel inhibitor |
WO2020219867A1 (en) | 2019-04-25 | 2020-10-29 | Vertex Pharmaceuticals Incorporated | Pyridone amide co-crystal compositions for the treatment of pain |
CN112390745B (zh) * | 2019-08-19 | 2022-10-21 | 江苏恒瑞医药股份有限公司 | 吡啶烟酰胺类衍生物、其制备方法及其在医药上的应用 |
AU2020346951A1 (en) * | 2019-09-12 | 2022-04-28 | Orion Corporation | Pyridine oxynitride, preparation method therefor and use thereof |
KR20220124176A (ko) | 2019-12-06 | 2022-09-13 | 버텍스 파마슈티칼스 인코포레이티드 | 나트륨 채널의 조절제로서의 치환된 테트라하이드로푸란 |
BR112023018313A2 (pt) * | 2021-03-11 | 2023-12-12 | Latigo Biotherapeutics Inc | Compostos de piridina e piridazina metil-substituída, derivados destes e métodos de seu uso |
EP4306511A1 (de) * | 2021-03-11 | 2024-01-17 | Shanghai Jemincare Pharmaceuticals Co., Ltd. | Kristallform einer pyridinstickstoffoxidverbindung und verwendung davon |
AU2022286511A1 (en) | 2021-06-04 | 2023-11-30 | Vertex Pharmaceuticals Incorporated | Hydroxy and (halo)alkoxy substituted tetrahydrofurans as modulators of sodium channels |
CN117813302A (zh) | 2021-06-04 | 2024-04-02 | 沃泰克斯药物股份有限公司 | 经取代的四氢呋喃-2-甲酰胺作为钠通道调节剂 |
EP4347584A1 (de) | 2021-06-04 | 2024-04-10 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl(hetero)aryl)tetrahydrofurancarboxamid-analoga als modulatoren von natriumkanälen |
AU2022284952A1 (en) | 2021-06-04 | 2023-12-14 | Vertex Pharmaceuticals Incorporated | Solid dosage forms and dosing regimens comprising (2r,3s,4s,5r)-4-[[3-(3,4-difluoro-2-methoxy-phenyl)-4,5-dimethyl-5-(trifluoromethyl) tetrahydrofuran-2-carbonyl]amino]pyridine-2-carboxamide |
AU2022284886A1 (en) | 2021-06-04 | 2023-11-30 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamides as modulators of sodium channels |
CN117794918A (zh) | 2021-06-04 | 2024-03-29 | 沃泰克斯药物股份有限公司 | 经取代的四氢呋喃类似物作为钠通道调节剂 |
CN116655497A (zh) * | 2022-02-25 | 2023-08-29 | 中国科学院上海药物研究所 | 脒类衍生化合物及其制备方法和用途 |
WO2023186102A1 (zh) * | 2022-04-02 | 2023-10-05 | 武汉人福创新药物研发中心有限公司 | Nav1.8抑制剂及其用途 |
WO2023205465A1 (en) | 2022-04-22 | 2023-10-26 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
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