TW201206900A - N-((6-amino-pyridin-3-yl)methyl)-heteroaryl-carboxamides - Google Patents

Info

Publication number

TW201206900A

TW201206900A TW100127620A TW100127620A TW201206900A TW 201206900 A TW201206900 A TW 201206900A TW 100127620 A TW100127620 A TW 100127620A TW 100127620 A TW100127620 A TW 100127620A TW 201206900 A TW201206900 A TW 201206900A

Authority

TW

Taiwan

Prior art keywords

amino

methyl

alkyl

group

indolyl

Prior art date

2010-08-04

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 claims abstract description 388
• 150000003839 salts Chemical group 0.000 claims abstract description 61
• 239000003814 drug Substances 0.000 claims abstract description 17
• 125000000217 alkyl group Chemical group 0.000 claims description 451
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 207
• -1 Oxyl Chemical group 0.000 claims description 160
• 125000004122 cyclic group Chemical group 0.000 claims description 157
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 140
• 229910052757 nitrogen Inorganic materials 0.000 claims description 131
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 124
• 229910052760 oxygen Inorganic materials 0.000 claims description 119
• 239000001301 oxygen Substances 0.000 claims description 119
• 229910052736 halogen Inorganic materials 0.000 claims description 103
• 150000002367 halogens Chemical class 0.000 claims description 99
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 90
• 229910052717 sulfur Inorganic materials 0.000 claims description 90
• 239000011593 sulfur Substances 0.000 claims description 89
• 125000003118 aryl group Chemical group 0.000 claims description 82
• 125000003545 alkoxy group Chemical group 0.000 claims description 80
• 125000001424 substituent group Chemical group 0.000 claims description 78
• 125000006413 ring segment Chemical group 0.000 claims description 76
• 125000005842 heteroatom Chemical group 0.000 claims description 65
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 63
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 58
• 150000001412 amines Chemical class 0.000 claims description 57
• 125000000623 heterocyclic group Chemical group 0.000 claims description 53
• 239000001257 hydrogen Substances 0.000 claims description 53
• 229910052739 hydrogen Inorganic materials 0.000 claims description 53
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 53
• 125000004434 sulfur atom Chemical group 0.000 claims description 50
• 125000003277 amino group Chemical group 0.000 claims description 44
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 42
• 125000001188 haloalkyl group Chemical group 0.000 claims description 42
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
• 239000000460 chlorine Substances 0.000 claims description 39
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 36
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
• 229920006395 saturated elastomer Polymers 0.000 claims description 36
• 201000010099 disease Diseases 0.000 claims description 35
• 125000002950 monocyclic group Chemical group 0.000 claims description 35
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 35
• 229910052799 carbon Inorganic materials 0.000 claims description 30
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 29
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 26
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 25
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 22
• 125000005843 halogen group Chemical group 0.000 claims description 22
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 22
• 125000001041 indolyl group Chemical group 0.000 claims description 21
• 108090000113 Plasma Kallikrein Proteins 0.000 claims description 20
• 125000004432 carbon atom Chemical group C* 0.000 claims description 20
• 102000003827 Plasma Kallikrein Human genes 0.000 claims description 19
• 239000007789 gas Substances 0.000 claims description 19
• 125000004429 atom Chemical group 0.000 claims description 18
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 18
• 125000003282 alkyl amino group Chemical group 0.000 claims description 16
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 16
• 125000000304 alkynyl group Chemical group 0.000 claims description 15
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 13
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 13
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 13
• 239000004202 carbamide Substances 0.000 claims description 12
• 125000000232 haloalkynyl group Chemical group 0.000 claims description 12
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
• 125000000262 haloalkenyl group Chemical group 0.000 claims description 11
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
• VAELWSLNTRVXQS-UHFFFAOYSA-N 1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=COC=N1 VAELWSLNTRVXQS-UHFFFAOYSA-N 0.000 claims description 10
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 10
• 125000006574 non-aromatic ring group Chemical group 0.000 claims description 10
• 239000011734 sodium Substances 0.000 claims description 10
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical group NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 claims description 9
• KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 9
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• 125000002947 alkylene group Chemical group 0.000 claims description 8
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 8
• BRBUBVKGJRPRRD-UHFFFAOYSA-N 4,6-dimethylpyridin-2-amine Chemical compound CC1=CC(C)=NC(N)=C1 BRBUBVKGJRPRRD-UHFFFAOYSA-N 0.000 claims description 7
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 7
• 125000003367 polycyclic group Chemical group 0.000 claims description 7
• 238000006467 substitution reaction Methods 0.000 claims description 7
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
• 239000011737 fluorine Substances 0.000 claims description 6
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 125000000879 imine group Chemical group 0.000 claims description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 5
• 150000002431 hydrogen Chemical class 0.000 claims description 5
• 230000001404 mediated effect Effects 0.000 claims description 5
• ZVXKYWHJBYIYNI-UHFFFAOYSA-N 1h-pyrazole-4-carboxamide Chemical compound NC(=O)C=1C=NNC=1 ZVXKYWHJBYIYNI-UHFFFAOYSA-N 0.000 claims description 4
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
• ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 4
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
• CBFCDTFDPHXCNY-UHFFFAOYSA-N octyldodecane Natural products CCCCCCCCCCCCCCCCCCCC CBFCDTFDPHXCNY-UHFFFAOYSA-N 0.000 claims description 4
• 150000002923 oximes Chemical class 0.000 claims description 4
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
• 229910052708 sodium Inorganic materials 0.000 claims description 4
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 4
• SSKZBZUASHFWGV-UHFFFAOYSA-N 6-amino-4-sulfanyl-1H-pyridine-2-thione Chemical compound Nc1cc(S)cc(=S)[nH]1 SSKZBZUASHFWGV-UHFFFAOYSA-N 0.000 claims description 3
• 150000003973 alkyl amines Chemical class 0.000 claims description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
• 229930192474 thiophene Natural products 0.000 claims description 3
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims description 2
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 2
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 2
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 2
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 6
• 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims 1
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 claims 1
• ACRGIRLCXXEJCS-UHFFFAOYSA-N 1h-indole-4-carboxamide Chemical compound NC(=O)C1=CC=CC2=C1C=CN2 ACRGIRLCXXEJCS-UHFFFAOYSA-N 0.000 claims 1
• CMFXKEDZAJBWJE-UHFFFAOYSA-N 3-benzyl-1,2-oxazole Chemical compound C=1C=CC=CC=1CC=1C=CON=1 CMFXKEDZAJBWJE-UHFFFAOYSA-N 0.000 claims 1
• 239000013543 active substance Substances 0.000 claims 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
• AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 claims 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
• 230000000052 comparative effect Effects 0.000 claims 1
• 125000006612 decyloxy group Chemical group 0.000 claims 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 210000003127 knee Anatomy 0.000 claims 1
• 229920005610 lignin Polymers 0.000 claims 1
• 229930182817 methionine Natural products 0.000 claims 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
• 239000008267 milk Substances 0.000 claims 1
• 210000004080 milk Anatomy 0.000 claims 1
• 235000013336 milk Nutrition 0.000 claims 1
• ICBKXGJJJQTUAY-UHFFFAOYSA-N nonan-4-amine Chemical compound CCCCCC(N)CCC ICBKXGJJJQTUAY-UHFFFAOYSA-N 0.000 claims 1
• 125000004076 pyridyl group Chemical group 0.000 claims 1
• 229910021653 sulphate ion Inorganic materials 0.000 claims 1
• 125000004149 thio group Chemical group *S* 0.000 claims 1
• 125000004001 thioalkyl group Chemical group 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 12
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 304
• 238000000034 method Methods 0.000 description 286
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• 238000004128 high performance liquid chromatography Methods 0.000 description 142
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• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 97
• 229910001868 water Inorganic materials 0.000 description 80
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• 239000000243 solution Substances 0.000 description 51
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• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 42
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 35
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• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
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• 238000001356 surgical procedure Methods 0.000 description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
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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 6
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• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
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