DK3122755T3 - UNKNOWN CONDENSED IMIDAZOBENZOTHIAZOL COMPOUNDS - Google Patents
UNKNOWN CONDENSED IMIDAZOBENZOTHIAZOL COMPOUNDS Download PDFInfo
- Publication number
- DK3122755T3 DK3122755T3 DK15717242.0T DK15717242T DK3122755T3 DK 3122755 T3 DK3122755 T3 DK 3122755T3 DK 15717242 T DK15717242 T DK 15717242T DK 3122755 T3 DK3122755 T3 DK 3122755T3
- Authority
- DK
- Denmark
- Prior art keywords
- alkyl
- imidazo
- tert
- butyl
- amino
- Prior art date
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- HWAXRLFNEXLBSN-UHFFFAOYSA-N 2h-imidazo[4,5-g][1,3]benzothiazole Chemical class C1=CC2=NCSC2=C2N=CN=C21 HWAXRLFNEXLBSN-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 265
- -1 CH2 halogen Chemical class 0.000 claims description 110
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 39
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 24
- 239000004202 carbamide Substances 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 208000006673 asthma Diseases 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 150000001204 N-oxides Chemical class 0.000 claims description 12
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 230000000172 allergic effect Effects 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 208000028004 allergic respiratory disease Diseases 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 8
- KYUNTDRHCPSMOG-UHFFFAOYSA-N 2h-1,3-benzothiazole-3-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)CSC2=C1 KYUNTDRHCPSMOG-UHFFFAOYSA-N 0.000 claims description 6
- 150000004677 hydrates Chemical class 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
- UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229910004727 OSO3H Inorganic materials 0.000 claims description 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000003003 spiro group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- LWFDHAPJWFIMIO-UHFFFAOYSA-N C(C)(C)(C)C1=NN(C(=C1)NC(=O)NC1=CC=C(C=C1)SC1=CC2=C(N3C(S2)=NC=C3C(=O)O)C=C1)C1=CC=C(C=C1)OC Chemical compound C(C)(C)(C)C1=NN(C(=C1)NC(=O)NC1=CC=C(C=C1)SC1=CC2=C(N3C(S2)=NC=C3C(=O)O)C=C1)C1=CC=C(C=C1)OC LWFDHAPJWFIMIO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 9
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 5
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 208000037915 non-allergic respiratory disease Diseases 0.000 claims 4
- SZXLBDVCHABEGD-UHFFFAOYSA-N 2h-1,3-benzothiazole-3-carboxamide Chemical compound C1=CC=C2N(C(=O)N)CSC2=C1 SZXLBDVCHABEGD-UHFFFAOYSA-N 0.000 claims 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 2
- SCMZUKWXQZOOQG-UHFFFAOYSA-N imidazo[2,1-b][1,3]benzothiazole-2-carboxamide Chemical compound C1=CC=C2N3C(SC2=C1)=NC(=C3)C(=O)N SCMZUKWXQZOOQG-UHFFFAOYSA-N 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 claims 1
- KXPKWHNZKVLCRR-UHFFFAOYSA-N 6-aminopyrimidine-4-carboxylic acid Chemical compound NC1=CC(C(O)=O)=NC=N1 KXPKWHNZKVLCRR-UHFFFAOYSA-N 0.000 claims 1
- PVHYQIUDYPJQGV-UHFFFAOYSA-N C(C)(C)(C)C1=NN(C(=C1)NC(=O)NC1=CC=C(C=C1)SC1=CC2=C(N3C(S2)=NC=C3C(=O)O)C=C1)C1=CC=C(C=C1)O Chemical compound C(C)(C)(C)C1=NN(C(=C1)NC(=O)NC1=CC=C(C=C1)SC1=CC2=C(N3C(S2)=NC=C3C(=O)O)C=C1)C1=CC=C(C=C1)O PVHYQIUDYPJQGV-UHFFFAOYSA-N 0.000 claims 1
- VQEUOGXRVDUBLN-UHFFFAOYSA-N COCC1=C(C)N=C2SC3=CC(OC4=C(CNC(=O)NC5=CC(=C(Cl)C=C5)C(F)(F)F)C=CC=C4)=CC=C3N12 Chemical compound COCC1=C(C)N=C2SC3=CC(OC4=C(CNC(=O)NC5=CC(=C(Cl)C=C5)C(F)(F)F)C=CC=C4)=CC=C3N12 VQEUOGXRVDUBLN-UHFFFAOYSA-N 0.000 claims 1
- YOIVKJOSQDFQFV-UHFFFAOYSA-N COCC1=C(C)N=C2SC3=CC(OC4=C(CNC(=O)NC5=CC(Cl)=C(OC)C=C5)C=CC=C4)=CC=C3N12 Chemical compound COCC1=C(C)N=C2SC3=CC(OC4=C(CNC(=O)NC5=CC(Cl)=C(OC)C=C5)C=CC=C4)=CC=C3N12 YOIVKJOSQDFQFV-UHFFFAOYSA-N 0.000 claims 1
- DATDJSZIZGCMBI-UHFFFAOYSA-N [4-[3-tert-butyl-5-[[2-[1-(morpholin-4-ylmethyl)imidazo[2,1-b][1,3]benzothiazol-6-yl]oxyphenyl]methylcarbamoylamino]pyrazol-1-yl]-2-chlorophenyl] hydrogen sulfate Chemical compound S(=O)(=O)(OC1=C(C=C(C=C1)N1N=C(C=C1NC(NCC1=C(C=CC=C1)OC1=CC2=C(N3C(S2)=NC=C3CN2CCOCC2)C=C1)=O)C(C)(C)C)Cl)O DATDJSZIZGCMBI-UHFFFAOYSA-N 0.000 claims 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 1
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- 239000002904 solvent Substances 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 238000000034 method Methods 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 37
- 125000000217 alkyl group Chemical group 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 28
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- 239000000203 mixture Substances 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 23
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 23
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 210000004072 lung Anatomy 0.000 description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 15
- 239000003981 vehicle Substances 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 210000000440 neutrophil Anatomy 0.000 description 12
- 239000000010 aprotic solvent Substances 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 201000010099 disease Diseases 0.000 description 9
- 239000012530 fluid Substances 0.000 description 9
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 9
- 239000000779 smoke Substances 0.000 description 9
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- 238000010520 demethylation reaction Methods 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 102000043136 MAP kinase family Human genes 0.000 description 7
- 108091054455 MAP kinase family Proteins 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 230000017858 demethylation Effects 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 208000037883 airway inflammation Diseases 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 235000019504 cigarettes Nutrition 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 6
- 210000004969 inflammatory cell Anatomy 0.000 description 6
- 230000004199 lung function Effects 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 230000002685 pulmonary effect Effects 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 5
- 241000208125 Nicotiana Species 0.000 description 5
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 5
- 208000010668 atopic eczema Diseases 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 210000000038 chest Anatomy 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- MMPNNHOCVBHUDP-UHFFFAOYSA-N CCOC(=O)C1=CN=C2SC3=CC(OC4=C(CO)C=CC=C4)=CC=C3N12 Chemical compound CCOC(=O)C1=CN=C2SC3=CC(OC4=C(CO)C=CC=C4)=CC=C3N12 MMPNNHOCVBHUDP-UHFFFAOYSA-N 0.000 description 4
- 241000700198 Cavia Species 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- QAGOQTLMBXVXKL-UHFFFAOYSA-N Cl.CCOC(=O)c1cnc2sc3cc(Oc4ccccc4CN)ccc3n12 Chemical compound Cl.CCOC(=O)c1cnc2sc3cc(Oc4ccccc4CN)ccc3n12 QAGOQTLMBXVXKL-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 4
- NNANLNTZKYFMRS-UHFFFAOYSA-N NC1=CC=C(OC2=CC3=C(N4C(S3)=NC=C4C(=O)OCC)C=C2)C=C1 Chemical compound NC1=CC=C(OC2=CC3=C(N4C(S3)=NC=C4C(=O)OCC)C=C2)C=C1 NNANLNTZKYFMRS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000001476 alcoholic effect Effects 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 229940125846 compound 25 Drugs 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
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- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
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- 239000011736 potassium bicarbonate Substances 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1089MU2014 | 2014-03-27 | ||
| PCT/IB2015/052124 WO2015145336A1 (en) | 2014-03-27 | 2015-03-24 | Novel fused imidazobenzothiazole compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK3122755T3 true DK3122755T3 (en) | 2019-02-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK15717242.0T DK3122755T3 (en) | 2014-03-27 | 2015-03-24 | UNKNOWN CONDENSED IMIDAZOBENZOTHIAZOL COMPOUNDS |
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| EP (1) | EP3122755B1 (enExample) |
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| AR (1) | AR099867A1 (enExample) |
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| CY (1) | CY1121147T1 (enExample) |
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| IL (1) | IL247955B (enExample) |
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| MY (1) | MY193041A (enExample) |
| PH (1) | PH12016501903B1 (enExample) |
| PL (1) | PL3122755T3 (enExample) |
| PT (1) | PT3122755T (enExample) |
| RS (1) | RS58324B1 (enExample) |
| SG (1) | SG11201607793RA (enExample) |
| SI (1) | SI3122755T1 (enExample) |
| SM (1) | SMT201900036T1 (enExample) |
| TR (1) | TR201900735T4 (enExample) |
| TW (1) | TWI648282B (enExample) |
| UA (1) | UA121469C2 (enExample) |
| WO (1) | WO2015145336A1 (enExample) |
| ZA (1) | ZA201606598B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2852054T3 (es) | 2013-03-15 | 2021-09-10 | Global Blood Therapeutics Inc | Compuestos y usos de los mismos para la modulación de hemoglobina |
| EA201992707A1 (ru) | 2013-11-18 | 2020-06-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| TWI648282B (zh) * | 2014-03-27 | 2019-01-21 | 印度商托仁特生技有限公司 | 新熔合咪唑苯并噻唑化合物 |
| DE102016209204A1 (de) | 2016-05-27 | 2017-11-30 | Robert Bosch Gmbh | Vorrichtung zur Regelung mindestens eines Fluidstroms in einem Fahrzeug |
| KR102630959B1 (ko) * | 2016-10-31 | 2024-01-29 | 엘지디스플레이 주식회사 | 유기 화합물과 이를 이용한 발광다이오드 및 유기발광다이오드 표시장치 |
| CN106727538A (zh) * | 2017-02-20 | 2017-05-31 | 潘连香 | 一种治疗2型糖尿病的药物组合物 |
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| GB8724566D0 (en) | 1987-10-20 | 1987-11-25 | Roussel Lab Ltd | Chemical compounds |
| GB8908845D0 (en) | 1989-04-19 | 1989-06-07 | Roussel Lab Ltd | Chemical compounds |
| AU2381995A (en) * | 1994-04-29 | 1995-11-29 | Pharmacia & Upjohn Company | Methanol derivatives for treatment of retroviral infections especially hiv infections |
| WO2002014321A1 (en) * | 2000-08-11 | 2002-02-21 | The Regents Of The University Of California | Use of stat-6 inhibitors as therapeutic agents |
| US7601846B2 (en) | 2001-06-26 | 2009-10-13 | The Regents Of The University Of California | Compounds having activity as inhibitors of apoptosis |
| JP2006513270A (ja) * | 2002-11-25 | 2006-04-20 | ファルマシア・コーポレーション | ヘテロアリールスルホニルメチルヒドロキサム酸およびアミド、ならびにプロテアーゼ阻害薬としてのそれらの使用 |
| GB0320244D0 (en) * | 2003-05-06 | 2003-10-01 | Aventis Pharma Inc | Pyrazoles as inhibitors of tumour necrosis factor |
| EP1984363A1 (en) * | 2006-02-09 | 2008-10-29 | Pfizer Limited | Triazolopyridine compounds |
| TWI648282B (zh) * | 2014-03-27 | 2019-01-21 | 印度商托仁特生技有限公司 | 新熔合咪唑苯并噻唑化合物 |
-
2015
- 2015-03-16 TW TW104108329A patent/TWI648282B/zh not_active IP Right Cessation
- 2015-03-24 PT PT15717242T patent/PT3122755T/pt unknown
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- 2015-03-24 DK DK15717242.0T patent/DK3122755T3/en active
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- 2015-03-24 AU AU2015237840A patent/AU2015237840B2/en not_active Ceased
- 2015-03-24 MX MX2016012535A patent/MX368985B/es active IP Right Grant
- 2015-03-24 TR TR2019/00735T patent/TR201900735T4/tr unknown
- 2015-03-24 CN CN201580024068.6A patent/CN106414458B/zh not_active Expired - Fee Related
- 2015-03-24 UA UAA201610628A patent/UA121469C2/uk unknown
- 2015-03-24 MY MYPI2016703533A patent/MY193041A/en unknown
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- 2015-03-24 PL PL15717242T patent/PL3122755T3/pl unknown
- 2015-03-24 US US15/128,886 patent/US9908898B2/en active Active
- 2015-03-24 EA EA201691920A patent/EA029745B9/ru not_active IP Right Cessation
- 2015-03-24 SI SI201530555T patent/SI3122755T1/sl unknown
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- 2015-03-24 SG SG11201607793RA patent/SG11201607793RA/en unknown
- 2015-03-24 EP EP15717242.0A patent/EP3122755B1/en active Active
- 2015-03-24 HR HRP20190121TT patent/HRP20190121T1/hr unknown
- 2015-03-24 SM SM20190036T patent/SMT201900036T1/it unknown
- 2015-03-24 JP JP2016559356A patent/JP6480949B2/ja not_active Expired - Fee Related
- 2015-03-24 ES ES15717242T patent/ES2707099T3/es active Active
- 2015-03-27 AR ARP150100915A patent/AR099867A1/es not_active Application Discontinuation
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2016
- 2016-09-21 IL IL247955A patent/IL247955B/en active IP Right Grant
- 2016-09-23 ZA ZA2016/06598A patent/ZA201606598B/en unknown
- 2016-09-27 PH PH12016501903A patent/PH12016501903B1/en unknown
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2018
- 2018-01-03 US US15/861,399 patent/US10227361B2/en active Active
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2019
- 2019-01-21 CY CY20191100076T patent/CY1121147T1/el unknown
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