CA2986199C - Benzoimidazole derivatives as pad4 inhibitors - Google Patents
Benzoimidazole derivatives as pad4 inhibitors Download PDFInfo
- Publication number
- CA2986199C CA2986199C CA2986199A CA2986199A CA2986199C CA 2986199 C CA2986199 C CA 2986199C CA 2986199 A CA2986199 A CA 2986199A CA 2986199 A CA2986199 A CA 2986199A CA 2986199 C CA2986199 C CA 2986199C
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- Prior art keywords
- methyl
- mmol
- indo1
- compound
- ethyl
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- 239000003112 inhibitor Substances 0.000 title abstract description 16
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical class C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 253
- 150000003839 salts Chemical class 0.000 claims abstract description 135
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 52
- 101100406797 Arabidopsis thaliana PAD4 gene Proteins 0.000 claims abstract description 44
- 101150094373 Padi4 gene Proteins 0.000 claims abstract description 44
- 102100035731 Protein-arginine deiminase type-4 Human genes 0.000 claims abstract description 44
- 238000011282 treatment Methods 0.000 claims abstract description 44
- 208000035475 disorder Diseases 0.000 claims abstract description 37
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 27
- 206010025135 lupus erythematosus Diseases 0.000 claims abstract description 24
- 206010047115 Vasculitis Diseases 0.000 claims abstract description 19
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 18
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 16
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 14
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 14
- 201000011510 cancer Diseases 0.000 claims abstract description 14
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims abstract description 14
- 201000003883 Cystic fibrosis Diseases 0.000 claims abstract description 13
- 208000006673 asthma Diseases 0.000 claims abstract description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 89
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 76
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 33
- 239000003814 drug Substances 0.000 claims description 31
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 230000000694 effects Effects 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 230000001404 mediated effect Effects 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 393
- 238000000034 method Methods 0.000 description 273
- 239000000543 intermediate Substances 0.000 description 222
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 220
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 219
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 180
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 154
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 150
- 229910001868 water Inorganic materials 0.000 description 149
- 238000006243 chemical reaction Methods 0.000 description 147
- 239000011541 reaction mixture Substances 0.000 description 144
- 239000000203 mixture Substances 0.000 description 128
- 239000000243 solution Substances 0.000 description 126
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 122
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 117
- 239000007787 solid Substances 0.000 description 112
- 239000002904 solvent Substances 0.000 description 104
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 94
- 239000000047 product Substances 0.000 description 93
- -1 -CH2CN Chemical group 0.000 description 89
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- 239000010410 layer Substances 0.000 description 76
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 74
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 71
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 63
- 235000019439 ethyl acetate Nutrition 0.000 description 61
- 239000012043 crude product Substances 0.000 description 59
- 239000000377 silicon dioxide Substances 0.000 description 59
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 58
- 239000003921 oil Substances 0.000 description 55
- 235000019198 oils Nutrition 0.000 description 54
- 238000003756 stirring Methods 0.000 description 52
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 51
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 48
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 47
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 46
- 230000002829 reductive effect Effects 0.000 description 45
- 239000000725 suspension Substances 0.000 description 45
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 238000000746 purification Methods 0.000 description 41
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 101100063435 Caenorhabditis elegans din-1 gene Proteins 0.000 description 39
- SBNOTUDDIXOFSN-UHFFFAOYSA-N 1h-indole-2-carbaldehyde Chemical compound C1=CC=C2NC(C=O)=CC2=C1 SBNOTUDDIXOFSN-UHFFFAOYSA-N 0.000 description 37
- 229910052938 sodium sulfate Inorganic materials 0.000 description 36
- 235000011152 sodium sulphate Nutrition 0.000 description 36
- 239000007832 Na2SO4 Substances 0.000 description 33
- 238000009472 formulation Methods 0.000 description 33
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- 150000002148 esters Chemical class 0.000 description 30
- 230000002209 hydrophobic effect Effects 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 30
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 25
- 239000000843 powder Substances 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 239000007821 HATU Substances 0.000 description 23
- 238000002347 injection Methods 0.000 description 22
- 239000007924 injection Substances 0.000 description 22
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 125000004093 cyano group Chemical group *C#N 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- 229940006116 lithium hydroxide Drugs 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 21
- BKXVVCILCIUCLG-UHFFFAOYSA-N raloxifene hydrochloride Chemical class [H+].[Cl-].C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 BKXVVCILCIUCLG-UHFFFAOYSA-N 0.000 description 20
- 239000000443 aerosol Substances 0.000 description 19
- 125000004429 atom Chemical group 0.000 description 19
- 239000002585 base Substances 0.000 description 19
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- 150000001299 aldehydes Chemical class 0.000 description 16
- 125000001475 halogen functional group Chemical group 0.000 description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
- 229910052796 boron Inorganic materials 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 15
- 239000000523 sample Substances 0.000 description 15
- 239000012312 sodium hydride Substances 0.000 description 15
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 14
- 238000004296 chiral HPLC Methods 0.000 description 14
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 14
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 14
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 14
- 230000008569 process Effects 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- 235000011054 acetic acid Nutrition 0.000 description 13
- 150000001242 acetic acid derivatives Chemical class 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000012530 fluid Substances 0.000 description 12
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 12
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 12
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 239000006071 cream Substances 0.000 description 11
- 239000002552 dosage form Substances 0.000 description 11
- WTDFFADXONGQOM-UHFFFAOYSA-N formaldehyde;hydrochloride Chemical class Cl.O=C WTDFFADXONGQOM-UHFFFAOYSA-N 0.000 description 11
- 150000002828 nitro derivatives Chemical class 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 10
- 239000003380 propellant Substances 0.000 description 10
- 239000012488 sample solution Substances 0.000 description 10
- WUOQXNWMYLFAHT-MRVPVSSYSA-N tert-butyl n-[(3r)-piperidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCCNC1 WUOQXNWMYLFAHT-MRVPVSSYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 238000012856 packing Methods 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 9
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 8
- 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 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- 238000011321 prophylaxis Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 238000000825 ultraviolet detection Methods 0.000 description 8
- 238000001851 vibrational circular dichroism spectroscopy Methods 0.000 description 8
- 239000012267 brine Substances 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 230000008878 coupling Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 239000000463 material Substances 0.000 description 7
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- 229920003023 plastic Polymers 0.000 description 7
- 239000004033 plastic Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000012453 solvate Substances 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000006329 citrullination Effects 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- 229940071648 metered dose inhaler Drugs 0.000 description 6
- RUJMPEWZLDVEAV-UHFFFAOYSA-N methyl 4-(methylamino)-3-nitrobenzoate Chemical compound CNC1=CC=C(C(=O)OC)C=C1[N+]([O-])=O RUJMPEWZLDVEAV-UHFFFAOYSA-N 0.000 description 6
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 6
- 210000001331 nose Anatomy 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 239000003643 water by type Substances 0.000 description 6
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 5
- NKWCGTOZTHZDHB-UHFFFAOYSA-N 1h-imidazol-1-ium-4-carboxylate Chemical compound OC(=O)C1=CNC=N1 NKWCGTOZTHZDHB-UHFFFAOYSA-N 0.000 description 5
- 101150041968 CDC13 gene Proteins 0.000 description 5
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 5
- 108010033040 Histones Proteins 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 102000004183 Synaptosomal-Associated Protein 25 Human genes 0.000 description 5
- 108010057722 Synaptosomal-Associated Protein 25 Proteins 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
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Classifications
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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Landscapes
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
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- General Health & Medical Sciences (AREA)
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- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Materials For Medical Uses (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA3199601A CA3199601A1 (en) | 2015-05-21 | 2016-05-19 | Benzoimidazole derivatives as pad4 inhibitors |
Applications Claiming Priority (3)
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| PCT/IB2016/000761 WO2016185279A1 (en) | 2015-05-21 | 2016-05-19 | Benzoimidazole derivatives as pad4 inhibitors |
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Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR107032A1 (es) * | 2015-12-09 | 2018-03-14 | Padlock Therapeutics Inc | Inhibidores bicíclicos de pad4 |
| CA3015482A1 (en) * | 2016-02-23 | 2017-08-31 | Padlock Therapeutics, Inc. | Heteroaryl inhibitors of pad4 |
| WO2018022897A1 (en) * | 2016-07-27 | 2018-02-01 | Padlock Therapeutics, Inc. | Covalent inhibitors of pad4 |
| CN110248934B (zh) | 2016-09-12 | 2022-05-24 | 帕德罗科治疗公司 | 杂芳基pad4抑制剂 |
| HUE067314T2 (hu) * | 2017-09-22 | 2024-10-28 | Jubilant Epipad LLC | Heterociklusos vegyületek mint PAD gátlók |
| KR102782563B1 (ko) * | 2017-10-18 | 2025-03-14 | 주빌런트 에피파드 엘엘씨 | Pad 억제제로서의 이미다조-피리딘 화합물 |
| KR20200085836A (ko) | 2017-11-06 | 2020-07-15 | 주빌런트 프로델 엘엘씨 | Pd1/pd-l1 활성화 억제제로서의 피리미딘 유도체 |
| BR112020010322A2 (pt) | 2017-11-24 | 2020-11-17 | Jubilant Episcribe Llc | composto da fórmula i; composto da fórmula ia; composto da fórmula ib; processo de preparação de compostos da fórmula i; composição farmacêutica; método para o tratamento e/ou prevenção de várias doenças; uso dos compostos; método para o tratamento de câncer; e método para o tratamento e/ou prevenção de uma afecção mediada por prmt5 ou um distúrbio proliferativo ou câncer |
| EP3737680A1 (en) | 2018-01-08 | 2020-11-18 | F. Hoffmann-La Roche AG | Octahydropyrido[1,2-alpha]pyrazines as magl inhibitors |
| WO2019152883A1 (en) * | 2018-02-02 | 2019-08-08 | Padforward Llc | Inhibitors of protein arginine deiminases |
| SG11202008950PA (en) | 2018-03-13 | 2020-10-29 | Jubilant Prodel LLC | Bicyclic compounds as inhibitors of pd1/pd-l1 interaction/activation |
| LT3768684T (lt) | 2018-03-22 | 2023-04-25 | F. Hoffmann-La Roche Ag | Oksazino monoacilglicerolio lipazės (magl) inhibitoriai |
| KR102885181B1 (ko) * | 2018-08-08 | 2025-11-11 | 브리스톨-마이어스 스큅 컴퍼니 | Pad 효소의 인돌 및 아자인돌 억제제 |
| SG11202101176YA (en) * | 2018-08-08 | 2021-03-30 | Bristol Myers Squibb Co | Substituted benzimidazoles as pad4 inhibitors |
| WO2020033514A1 (en) * | 2018-08-08 | 2020-02-13 | Bristol-Myers Squibb Company | Benzimidazole inhibitors of pad enzymes |
| ES2929200T3 (es) | 2018-08-08 | 2022-11-25 | Bristol Myers Squibb Co | Tienopirroles sustituidos como inhibidores de PAD4 |
| KR20210044217A (ko) | 2018-08-13 | 2021-04-22 | 에프. 호프만-라 로슈 아게 | 모노아실글리세롤 리파제 저해제로서의 신규 헤테로시클릭 화합물 |
| EP4474017A3 (en) | 2018-08-13 | 2025-02-26 | F. Hoffmann-La Roche AG | New heterocyclic compounds |
| CN113166170A (zh) | 2018-11-22 | 2021-07-23 | 豪夫迈·罗氏有限公司 | 新的杂环化合物 |
| US20210094971A1 (en) | 2019-09-09 | 2021-04-01 | Hoffmann-La Roche Inc. | Heterocyclic compounds |
| WO2021048242A1 (en) | 2019-09-12 | 2021-03-18 | F. Hoffmann-La Roche Ag | 4,4a,5,7,8,8a-hexapyrido[4,3-b][1,4]oxazin-3-one compounds as magl inhibitors |
| EP4034602A1 (en) | 2019-09-24 | 2022-08-03 | F. Hoffmann-La Roche AG | Fluorescent probes for monoacylglycerol lipase (magl) |
| CA3152213A1 (en) | 2019-09-24 | 2021-04-01 | F. Hoffmann-La Roche Ag | New heterocyclic monoacylglycerol lipase (magl) inhibitors |
| PE20221340A1 (es) | 2019-09-24 | 2022-09-13 | Hoffmann La Roche | Compuestos heterociclicos |
| WO2021057910A1 (zh) * | 2019-09-27 | 2021-04-01 | 南京药捷安康生物科技有限公司 | 肽酰精氨酸脱亚胺酶抑制剂及其用途 |
| KR20220137694A (ko) * | 2020-02-06 | 2022-10-12 | 브리스톨-마이어스 스큅 컴퍼니 | 면역억제제로서 유용한 마크로시클릭 pad4 억제제 |
| TW202140477A (zh) * | 2020-02-12 | 2021-11-01 | 美商必治妥美雅史谷比公司 | 雜環ｐａｄ４抑制劑 |
| US20230107927A1 (en) | 2020-02-28 | 2023-04-06 | First Wave Bio, Inc. | Methods of treating iatrogenic autoimmune colitis |
| MX2022013615A (es) * | 2020-04-30 | 2022-11-16 | Gilead Sciences Inc | Inhibidores de macrociclo de peptidilarginina deiminasas. |
| MX2023001671A (es) * | 2020-08-12 | 2023-05-16 | Jubilant Epipad LLC | Procedimiento y compuesto para su uso en el tratamiento y/o prevención de la netosis. |
| CA3190277A1 (en) | 2020-09-03 | 2022-03-10 | Joerg Benz | Heterocyclic compounds |
| TW202233174A (zh) | 2020-12-22 | 2022-09-01 | 美商基利科學股份有限公司 | 肽基精胺酸去亞胺酶之抑制劑 |
| TW202241884A (zh) | 2020-12-22 | 2022-11-01 | 美商基利科學股份有限公司 | 肽基精胺酸去亞胺酶之抑制劑 |
| AU2022387714A1 (en) * | 2021-11-15 | 2024-05-30 | Regor Pharmaceuticals, Inc. | Pad4 inhibitors and use thereof |
| WO2025024265A1 (en) | 2023-07-21 | 2025-01-30 | Bristol-Myers Squibb Company | Methods of assessing citrullination and activity of pad4 modulators |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU570439B2 (en) | 1983-03-28 | 1988-03-17 | Compression Labs, Inc. | A combined intraframe and interframe transform coding system |
| US5776963A (en) | 1989-05-19 | 1998-07-07 | Hoechst Marion Roussel, Inc. | 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility |
| AU710382B2 (en) | 1995-04-14 | 1999-09-16 | Glaxo Wellcome Inc. | Metered dose inhaler for albuterol |
| TW533865U (en) | 1997-06-10 | 2003-05-21 | Glaxo Group Ltd | Dispenser for dispensing medicament and actuation indicating device |
| US6315112B1 (en) | 1998-12-18 | 2001-11-13 | Smithkline Beecham Corporation | Method and package for storing a pressurized container containing a drug |
| US6119853A (en) | 1998-12-18 | 2000-09-19 | Glaxo Wellcome Inc. | Method and package for storing a pressurized container containing a drug |
| US6390291B1 (en) | 1998-12-18 | 2002-05-21 | Smithkline Beecham Corporation | Method and package for storing a pressurized container containing a drug |
| US6352152B1 (en) | 1998-12-18 | 2002-03-05 | Smithkline Beecham Corporation | Method and package for storing a pressurized container containing a drug |
| US6448281B1 (en) * | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| BR0213562A (pt) * | 2001-10-26 | 2004-08-31 | Aventis Pharma Inc | Benzimidazóis e análogos e seu uso como inibidores de cinases de proteìna |
| JP4641526B2 (ja) | 2003-11-03 | 2011-03-02 | グラクソ グループ リミテッド | 流体分配デバイス |
| US7429611B2 (en) * | 2004-09-23 | 2008-09-30 | Bristol-Myers Squibb Company | Indole inhibitors of 15-lipoxygenase |
| UY32138A (es) | 2008-09-25 | 2010-04-30 | Boehringer Ingelheim Int | Amidas sustituidas del ácido 2-(2,6-dicloro-fenilamino)-6-fluoro-1-metil-1h-bencimidazol-5-carboxílico y sus sales farmacéuticamente aceptables |
| WO2010115736A2 (en) * | 2009-04-02 | 2010-10-14 | Merck Serono S.A. | Dihydroorotate dehydrogenase inhibitors |
| US8450340B2 (en) * | 2009-12-21 | 2013-05-28 | Samumed, Llc | 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof |
| US9127003B2 (en) * | 2012-07-26 | 2015-09-08 | Glaxo Group Limited | 2-(azaindol-2-yl)benzimidazoles as PAD4 inhibitors |
| AR107032A1 (es) * | 2015-12-09 | 2018-03-14 | Padlock Therapeutics Inc | Inhibidores bicíclicos de pad4 |
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| TW201706263A (zh) | 2017-02-16 |
| AU2016264958A1 (en) | 2017-12-07 |
| CN107849015B (zh) | 2021-03-19 |
| CA3199601A1 (en) | 2016-11-24 |
| KR20180005250A (ko) | 2018-01-15 |
| BR112017024678A2 (pt) | 2018-07-31 |
| CN107849015A (zh) | 2018-03-27 |
| EA033680B1 (ru) | 2019-11-15 |
| EP3298003A1 (en) | 2018-03-28 |
| US10815218B2 (en) | 2020-10-27 |
| IL278916A (en) | 2021-01-31 |
| JP6703553B2 (ja) | 2020-06-03 |
| MX387321B (es) | 2025-03-11 |
| AR106863A1 (es) | 2018-02-28 |
| US10407407B2 (en) | 2019-09-10 |
| AU2016264958B2 (en) | 2020-10-29 |
| WO2016185279A1 (en) | 2016-11-24 |
| US20200095227A1 (en) | 2020-03-26 |
| ES2945314T3 (es) | 2023-06-30 |
| US20180297983A1 (en) | 2018-10-18 |
| EP3298003B1 (en) | 2023-04-19 |
| EA201792517A1 (ru) | 2018-04-30 |
| MX2017014714A (es) | 2018-01-25 |
| JP2018520105A (ja) | 2018-07-26 |
| IL255666A (en) | 2018-01-31 |
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