BG65860B1 - Заместени пиридини и пиридазини, инхибиращи ангиогенезата - Google Patents

Info

Publication number

BG65860B1

BG65860B1 BG106637A BG10663702A BG65860B1 BG 65860 B1 BG65860 B1 BG 65860B1 BG 106637 A BG106637 A BG 106637A BG 10663702 A BG10663702 A BG 10663702A BG 65860 B1 BG65860 B1 BG 65860B1

Authority

BG

Bulgaria

Prior art keywords

alkyl

substituted

optionally substituted

methyl

amino

Prior art date

1999-09-28

Links

• Espacenet
• Global Dossier
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• 230000033115 angiogenesis Effects 0.000 title claims abstract description 23
• 230000002401 inhibitory effect Effects 0.000 title abstract description 3
• 150000004892 pyridazines Chemical class 0.000 title description 4
• 150000003222 pyridines Chemical class 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 135
• 238000000034 method Methods 0.000 claims abstract description 113
• 125000001424 substituent group Chemical group 0.000 claims abstract description 59
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 31
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 27
• 125000003118 aryl group Chemical group 0.000 claims abstract description 23
• 230000008569 process Effects 0.000 claims abstract description 8
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• 125000003282 alkyl amino group Chemical group 0.000 claims description 133
• -1 nitro, amidino, guanidino, mercapto, sulfo Chemical group 0.000 claims description 108
• 125000000217 alkyl group Chemical group 0.000 claims description 101
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 81
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
• 229910052717 sulfur Inorganic materials 0.000 claims description 64
• 125000000623 heterocyclic group Chemical group 0.000 claims description 63
• 229910052760 oxygen Inorganic materials 0.000 claims description 62
• 125000004429 atom Chemical group 0.000 claims description 55
• 125000001072 heteroaryl group Chemical group 0.000 claims description 52
• 238000002360 preparation method Methods 0.000 claims description 51
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 44
• 229910052757 nitrogen Inorganic materials 0.000 claims description 44
• 229910052736 halogen Inorganic materials 0.000 claims description 42
• 125000004432 carbon atom Chemical group C* 0.000 claims description 38
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 38
• 125000003545 alkoxy group Chemical group 0.000 claims description 32
• 125000004414 alkyl thio group Chemical group 0.000 claims description 31
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
• 125000003107 substituted aryl group Chemical group 0.000 claims description 29
• 150000002367 halogens Chemical class 0.000 claims description 27
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 27
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 22
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 22
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 21
• 230000015572 biosynthetic process Effects 0.000 claims description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 125000003342 alkenyl group Chemical group 0.000 claims description 16
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 15
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 14
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
• 150000001412 amines Chemical class 0.000 claims description 14
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 14
• 125000003277 amino group Chemical group 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 12
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 12
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 11
• 125000005842 heteroatom Chemical group 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 10
• 241000124008 Mammalia Species 0.000 claims description 9
• 125000002947 alkylene group Chemical group 0.000 claims description 9
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 125000004423 acyloxy group Chemical group 0.000 claims description 7
• 125000006413 ring segment Chemical group 0.000 claims description 7
• 125000004434 sulfur atom Chemical group 0.000 claims description 7
• 230000002159 abnormal effect Effects 0.000 claims description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
• 206010038923 Retinopathy Diseases 0.000 claims description 5
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 208000028867 ischemia Diseases 0.000 claims description 5
• 229910052751 metal Inorganic materials 0.000 claims description 5
• 239000002184 metal Substances 0.000 claims description 5
• 206010006555 Bullous conditions Diseases 0.000 claims description 4
• 201000004624 Dermatitis Diseases 0.000 claims description 4
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
• 206010015150 Erythema Diseases 0.000 claims description 4
• 206010034277 Pemphigoid Diseases 0.000 claims description 4
• 208000017442 Retinal disease Diseases 0.000 claims description 4
• 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 4
• 238000011161 development Methods 0.000 claims description 4
• 230000018109 developmental process Effects 0.000 claims description 4
• 231100000321 erythema Toxicity 0.000 claims description 4
• 238000005304 joining Methods 0.000 claims description 4
• 208000002780 macular degeneration Diseases 0.000 claims description 4
• 210000001957 retinal vein Anatomy 0.000 claims description 4
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• ZNBJYZFRLKDRAC-UHFFFAOYSA-N 4-[[1-(4-chloroanilino)isoquinolin-4-yl]methyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC(CC=2C3=CC=CC=C3C(NC=3C=CC(Cl)=CC=3)=NC=2)=C1 ZNBJYZFRLKDRAC-UHFFFAOYSA-N 0.000 claims description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
• UFGSVJMWQZYRDS-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-5-yl)-4-(pyridin-4-ylmethyl)isoquinolin-1-amine Chemical compound C=1N=C(NC=2C=C3CCCC3=CC=2)C2=CC=CC=C2C=1CC1=CC=NC=C1 UFGSVJMWQZYRDS-UHFFFAOYSA-N 0.000 claims description 2
• GHEQDWPWNIMUQE-UHFFFAOYSA-N n-(3-fluoro-4-methylphenyl)-4-(pyridin-4-ylmethyl)isoquinolin-1-amine Chemical compound C1=C(F)C(C)=CC=C1NC(C1=CC=CC=C11)=NC=C1CC1=CC=NC=C1 GHEQDWPWNIMUQE-UHFFFAOYSA-N 0.000 claims description 2
• DFVKSVPVYDYCCD-UHFFFAOYSA-N n-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)isoquinolin-1-amine Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NC=C1CC1=CC=NC=C1 DFVKSVPVYDYCCD-UHFFFAOYSA-N 0.000 claims description 2
• DIDIJDSQKHOKKS-UHFFFAOYSA-N n-(4-chlorophenyl)-4-pyridin-4-ylsulfanylisoquinolin-1-amine Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NC=C1SC1=CC=NC=C1 DIDIJDSQKHOKKS-UHFFFAOYSA-N 0.000 claims description 2
• VNRMXOPCEVMSCQ-UHFFFAOYSA-N n-(4-pyridin-4-ylsulfanylisoquinolin-1-yl)-1,3-benzothiazol-6-amine Chemical compound C=1C=C2N=CSC2=CC=1NC(C1=CC=CC=C11)=NC=C1SC1=CC=NC=C1 VNRMXOPCEVMSCQ-UHFFFAOYSA-N 0.000 claims description 2
• PXRQCAHBDKPEKP-UHFFFAOYSA-N n-[4-(pyridin-4-ylmethyl)isoquinolin-1-yl]-1,3-benzothiazol-6-amine Chemical compound C=1N=C(NC=2C=C3SC=NC3=CC=2)C2=CC=CC=C2C=1CC1=CC=NC=C1 PXRQCAHBDKPEKP-UHFFFAOYSA-N 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 11
• 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 10
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 6
• 201000004681 Psoriasis Diseases 0.000 claims 3
• LUCGBEPEAUHERV-UHFFFAOYSA-N pyridazin-4-amine Chemical compound NC1=CC=NN=C1 LUCGBEPEAUHERV-UHFFFAOYSA-N 0.000 claims 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 2
• 230000005748 tumor development Effects 0.000 claims 2
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
• NQHPPUGCFAAXNN-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide;hydrobromide Chemical compound Br.C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 NQHPPUGCFAAXNN-UHFFFAOYSA-N 0.000 claims 1
• RJWBTWIBUIGANW-UHFFFAOYSA-M 4-chlorobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-M 0.000 claims 1
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
• 229910002651 NO3 Inorganic materials 0.000 claims 1
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• 150000003857 carboxamides Chemical class 0.000 claims 1
• 150000002466 imines Chemical class 0.000 claims 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 claims 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
• IKTMLCHVAZTPSB-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]pyridine-2-carboxamide Chemical compound CN(C)CCNC(=O)C1=CC=CC=N1 IKTMLCHVAZTPSB-UHFFFAOYSA-N 0.000 claims 1
• UVVSPCBTTAHCDX-UHFFFAOYSA-N n-[4-(5-bromo-2,3-dihydroindol-1-yl)phthalazin-1-yl]-1,3-benzothiazol-6-amine Chemical compound C12=CC=CC=C2C(N2C3=CC=C(C=C3CC2)Br)=NN=C1NC1=CC=C(N=CS2)C2=C1 UVVSPCBTTAHCDX-UHFFFAOYSA-N 0.000 claims 1
• SJXFRBJTCADHHF-UHFFFAOYSA-N n-cyclopropylpyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)NC1CC1 SJXFRBJTCADHHF-UHFFFAOYSA-N 0.000 claims 1
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• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims 1
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