SK89496A3 - Bicyclic compounds, pharmaceutical compositions on their base and preventing method of blastocyst implantation - Google Patents

Bicyclic compounds, pharmaceutical compositions on their base and preventing method of blastocyst implantation Download PDF

Info

Publication number: SK89496A3
Authority: SK; Slovakia
Prior art keywords: carbon atoms; alkyl; mono; carbon; group
Prior art date: 1994-01-25

Application number

SK894-96A

Other languages

English (en)

Slovak (sk)

Inventor

Alexander J Bridges

William A Denny

David Fry

Alan Kraker

Robert Meyer

Gordon W Rewcastle

Andrew M Thompson

Original Assignee

Warner Lambert Co

Priority date (The priority date 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 date listed.)

1994-01-25

Filing date

1995-01-23

Publication date

1997-10-08

1994-12-23 Priority claimed from US08/358,351 external-priority patent/US5654307A/en

1995-01-23 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

1997-10-08 Publication of SK89496A3 publication Critical patent/SK89496A3/sk

Links

238000000034 method Methods 0.000 title claims description 70
125000002619 bicyclic group Chemical group 0.000 title claims description 11
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
230000032692 embryo implantation Effects 0.000 title 1
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 541
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 316
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 234
125000000217 alkyl group Chemical group 0.000 claims abstract description 215
229910052799 carbon Inorganic materials 0.000 claims abstract description 181
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 150
125000003545 alkoxy group Chemical group 0.000 claims abstract description 107
125000004429 atom Chemical group 0.000 claims abstract description 53
229910052717 sulfur Inorganic materials 0.000 claims abstract description 51
229910052760 oxygen Inorganic materials 0.000 claims abstract description 33
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims abstract description 28
101800003838 Epidermal growth factor Proteins 0.000 claims abstract description 27
229940116977 epidermal growth factor Drugs 0.000 claims abstract description 27
125000005842 heteroatom Chemical group 0.000 claims abstract description 12
102000009024 Epidermal Growth Factor Human genes 0.000 claims abstract 2
229910052739 hydrogen Inorganic materials 0.000 claims description 191
-1 hydroxy, amino Chemical group 0.000 claims description 184
239000000203 mixture Substances 0.000 claims description 128
125000003118 aryl group Chemical group 0.000 claims description 123
102000001301 EGF receptor Human genes 0.000 claims description 110
239000001257 hydrogen Substances 0.000 claims description 109
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 109
108060006698 EGF receptor Proteins 0.000 claims description 108
150000001875 compounds Chemical class 0.000 claims description 107
125000004663 dialkyl amino group Chemical group 0.000 claims description 96
150000003839 salts Chemical class 0.000 claims description 84
239000003814 drug Substances 0.000 claims description 83
125000000753 cycloalkyl group Chemical group 0.000 claims description 82
125000001041 indolyl group Chemical group 0.000 claims description 82
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 77
229960001231 choline Drugs 0.000 claims description 77
125000004433 nitrogen atom Chemical group N* 0.000 claims description 75
125000001841 imino group Chemical group [H]N=* 0.000 claims description 74
150000002431 hydrogen Chemical class 0.000 claims description 72
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 72
230000002401 inhibitory effect Effects 0.000 claims description 70
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 67
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 66
125000003277 amino group Chemical group 0.000 claims description 60
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 41
125000001424 substituent group Chemical group 0.000 claims description 39
125000002541 furyl group Chemical group 0.000 claims description 36
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 33
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 28
125000003342 alkenyl group Chemical group 0.000 claims description 26
150000001721 carbon Chemical group 0.000 claims description 26
229910052801 chlorine Inorganic materials 0.000 claims description 25
JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 24
125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 24
125000004423 acyloxy group Chemical group 0.000 claims description 24
125000004193 piperazinyl group Chemical group 0.000 claims description 24
125000005936 piperidyl group Chemical group 0.000 claims description 24
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 24
125000001166 thiolanyl group Chemical group 0.000 claims description 24
125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 23
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 23
239000011593 sulfur Substances 0.000 claims description 23
125000004001 thioalkyl group Chemical group 0.000 claims description 23
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 21
229910052736 halogen Inorganic materials 0.000 claims description 21
150000002367 halogens Chemical class 0.000 claims description 21
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
239000000460 chlorine Substances 0.000 claims description 20
229910052731 fluorine Inorganic materials 0.000 claims description 20
150000003254 radicals Chemical class 0.000 claims description 19
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 18
239000001301 oxygen Substances 0.000 claims description 18
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 16
229910052794 bromium Inorganic materials 0.000 claims description 15
230000005764 inhibitory process Effects 0.000 claims description 15
125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
125000004442 acylamino group Chemical group 0.000 claims description 13
125000002971 oxazolyl group Chemical group 0.000 claims description 13
125000004430 oxygen atom Chemical group O* 0.000 claims description 13
125000000168 pyrrolyl group Chemical group 0.000 claims description 13
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 13
125000002252 acyl group Chemical group 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
125000005276 alkyl hydrazino group Chemical group 0.000 claims description 12
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 12
125000004093 cyano group Chemical group *C#N 0.000 claims description 12
125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 12
125000001624 naphthyl group Chemical group 0.000 claims description 12
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 12
125000003373 pyrazinyl group Chemical group 0.000 claims description 12
125000004076 pyridyl group Chemical group 0.000 claims description 12
125000000335 thiazolyl group Chemical group 0.000 claims description 12
125000001544 thienyl group Chemical group 0.000 claims description 12
JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 12
125000000304 alkynyl group Chemical group 0.000 claims description 11
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 11
239000011737 fluorine Substances 0.000 claims description 11
125000004963 sulfonylalkyl group Chemical group 0.000 claims description 11
125000004434 sulfur atom Chemical group 0.000 claims description 11
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
229910052740 iodine Inorganic materials 0.000 claims description 10
206010028980 Neoplasm Diseases 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
241000124008 Mammalia Species 0.000 claims description 8
125000005587 carbonate group Chemical group 0.000 claims description 8
210000001109 blastomere Anatomy 0.000 claims description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
125000005518 carboxamido group Chemical group 0.000 claims description 6
229940079593 drug Drugs 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
201000004681 Psoriasis Diseases 0.000 claims description 5
201000011510 cancer Diseases 0.000 claims description 5
PVCHTGBTKFGXJK-UHFFFAOYSA-N n-[4-(benzylamino)pyrido[4,3-d]pyrimidin-7-yl]acetamide Chemical compound C=12C=NC(NC(=O)C)=CC2=NC=NC=1NCC1=CC=CC=C1 PVCHTGBTKFGXJK-UHFFFAOYSA-N 0.000 claims description 5
QFXMHNZCUIIRHD-UHFFFAOYSA-N 4-n-(3-bromophenyl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC1=CC=CC(Br)=C1 QFXMHNZCUIIRHD-UHFFFAOYSA-N 0.000 claims description 4
MKXXQHSAJJMCBR-UHFFFAOYSA-N 4-n-(3-bromophenyl)-6-n-methylpyrido[3,2-d]pyrimidine-4,6-diamine Chemical compound C12=NC(NC)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 MKXXQHSAJJMCBR-UHFFFAOYSA-N 0.000 claims description 4
PWLAEHXFQCNKSK-UHFFFAOYSA-N 4-n-(3-bromophenyl)pyrido[3,2-d]pyrimidine-4,6-diamine Chemical compound C12=NC(N)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 PWLAEHXFQCNKSK-UHFFFAOYSA-N 0.000 claims description 4
SFUYILVZGXHCDG-UHFFFAOYSA-N 4-n-(3-bromophenyl)pyrido[4,3-d]pyrimidine-4,7-diamine Chemical compound C=12C=NC(N)=CC2=NC=NC=1NC1=CC=CC(Br)=C1 SFUYILVZGXHCDG-UHFFFAOYSA-N 0.000 claims description 4
YJJIALJNKYISIO-UHFFFAOYSA-N 4-n-(4-bromophenyl)pyrido[4,3-d]pyrimidine-4,7-diamine Chemical compound C=12C=NC(N)=CC2=NC=NC=1NC1=CC=C(Br)C=C1 YJJIALJNKYISIO-UHFFFAOYSA-N 0.000 claims description 4
UCCQIOAGMXPOET-UHFFFAOYSA-N 4-n-[3-(trifluoromethyl)phenyl]pyrido[4,3-d]pyrimidine-4,7-diamine Chemical compound C=12C=NC(N)=CC2=NC=NC=1NC1=CC=CC(C(F)(F)F)=C1 UCCQIOAGMXPOET-UHFFFAOYSA-N 0.000 claims description 4
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 4
KFHMLBXBRCITHF-UHFFFAOYSA-N PD158780 Chemical compound N1=CN=C2C=NC(NC)=CC2=C1NC1=CC=CC(Br)=C1 KFHMLBXBRCITHF-UHFFFAOYSA-N 0.000 claims description 4
102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 4
108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 4
238000002513 implantation Methods 0.000 claims description 4
VUFZZYOKJHFSAA-UHFFFAOYSA-N 4-n-(3-bromophenyl)-6-n,6-n-dimethylpyrido[3,2-d]pyrimidine-4,6-diamine Chemical compound C12=NC(N(C)C)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 VUFZZYOKJHFSAA-UHFFFAOYSA-N 0.000 claims description 3
BMZXYZGEVIZRKF-UHFFFAOYSA-N 4-n-(3-nitrophenyl)pyrido[4,3-d]pyrimidine-4,7-diamine Chemical compound C=12C=NC(N)=CC2=NC=NC=1NC1=CC=CC([N+]([O-])=O)=C1 BMZXYZGEVIZRKF-UHFFFAOYSA-N 0.000 claims description 3
206010033645 Pancreatitis Diseases 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
208000017169 kidney disease Diseases 0.000 claims description 3
APXDAYLGZSXVDB-UHFFFAOYSA-N n-(3-bromophenyl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC1=CC=CC(Br)=C1 APXDAYLGZSXVDB-UHFFFAOYSA-N 0.000 claims description 3
KKLFLZHHIPZMHQ-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[4,3-d]pyrimidin-7-yl]acetamide Chemical compound C=12C=NC(NC(=O)C)=CC2=NC=NC=1NC1=CC=CC(Br)=C1 KKLFLZHHIPZMHQ-UHFFFAOYSA-N 0.000 claims description 3
XZPCYVKAGQFORE-UHFFFAOYSA-N n-benzylpyrido[4,3-d]pyrimidin-4-amine Chemical compound N=1C=NC2=CC=NC=C2C=1NCC1=CC=CC=C1 XZPCYVKAGQFORE-UHFFFAOYSA-N 0.000 claims description 3
108091008598 receptor tyrosine kinases Proteins 0.000 claims description 3
125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
FJNCXZZQNBKEJT-UHFFFAOYSA-N 8beta-hydroxymarrubiin Natural products O1C(=O)C2(C)CCCC3(C)C2C1CC(C)(O)C3(O)CCC=1C=COC=1 FJNCXZZQNBKEJT-UHFFFAOYSA-N 0.000 claims description 2
230000002254 contraceptive effect Effects 0.000 claims description 2
ODVAMUDYBBPTAL-UHFFFAOYSA-N n-(3-bromophenyl)-6-methoxypyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(OC)=CC2=C1NC1=CC=CC(Br)=C1 ODVAMUDYBBPTAL-UHFFFAOYSA-N 0.000 claims description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 2
150000004677 hydrates Chemical class 0.000 claims 75
125000000000 cycloalkoxy group Chemical group 0.000 claims 22
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 20
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 3
APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 claims 3
125000005493 quinolyl group Chemical group 0.000 claims 3
239000003085 diluting agent Substances 0.000 claims 2
239000000546 pharmaceutical excipient Substances 0.000 claims 2
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
JHWNCZPTCROSRX-UHFFFAOYSA-N 1-piperidin-1-ylpyridin-1-ium Chemical compound C1CCCCN1[N+]1=CC=CC=C1 JHWNCZPTCROSRX-UHFFFAOYSA-N 0.000 claims 1
108091005682 Receptor kinases Proteins 0.000 claims 1
125000004181 carboxyalkyl group Chemical group 0.000 claims 1
239000003433 contraceptive agent Substances 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
WYOFJYXGKWRDKC-UHFFFAOYSA-N n-(3-bromophenyl)thieno[2,3-d]pyrimidin-4-amine Chemical compound BrC1=CC=CC(NC=2C=3C=CSC=3N=CN=2)=C1 WYOFJYXGKWRDKC-UHFFFAOYSA-N 0.000 claims 1
IKDNMRVPNRIVPS-UHFFFAOYSA-N n-(3-bromophenyl)thieno[3,2-d]pyrimidin-4-amine Chemical compound BrC1=CC=CC(NC=2C=3SC=CC=3N=CN=2)=C1 IKDNMRVPNRIVPS-UHFFFAOYSA-N 0.000 claims 1
HXYUHSIGXJQOND-UHFFFAOYSA-N n-benzylthieno[3,2-d]pyrimidin-4-amine Chemical compound N=1C=NC=2C=CSC=2C=1NCC1=CC=CC=C1 HXYUHSIGXJQOND-UHFFFAOYSA-N 0.000 claims 1
102000027426 receptor tyrosine kinases Human genes 0.000 claims 1
239000003112 inhibitor Substances 0.000 abstract description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 286
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 115
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
239000007787 solid Substances 0.000 description 93
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
239000000243 solution Substances 0.000 description 60
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
210000004027 cell Anatomy 0.000 description 52
238000006243 chemical reaction Methods 0.000 description 49
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
239000000047 product Substances 0.000 description 45
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
239000003480 eluent Substances 0.000 description 39
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 37
239000000741 silica gel Substances 0.000 description 36
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238000006073 displacement reaction Methods 0.000 description 35
230000002829 reductive effect Effects 0.000 description 34
JHZDQHOTYTUIII-UHFFFAOYSA-N 4-methylsulfanylpyrido[4,3-d]pyrimidin-7-amine Chemical compound NC1=NC=C2C(SC)=NC=NC2=C1 JHZDQHOTYTUIII-UHFFFAOYSA-N 0.000 description 32
150000001412 amines Chemical class 0.000 description 29
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 26
102400001368 Epidermal growth factor Human genes 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
230000000694 effects Effects 0.000 description 20
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 20
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 19
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 19
238000010992 reflux Methods 0.000 description 19
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
238000009833 condensation Methods 0.000 description 18
230000005494 condensation Effects 0.000 description 18
239000000284 extract Substances 0.000 description 18
239000002904 solvent Substances 0.000 description 18
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 17
239000002244 precipitate Substances 0.000 description 17
102000005962 receptors Human genes 0.000 description 17
108020003175 receptors Proteins 0.000 description 17
238000003756 stirring Methods 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
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FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
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GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
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RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
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
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical compound C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
FKKJJPMGAWGYPN-UHFFFAOYSA-N thiophen-2-ylmethanamine Chemical compound NCC1=CC=CS1 FKKJJPMGAWGYPN-UHFFFAOYSA-N 0.000 description 1
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LGSAOJLQTXCYHF-UHFFFAOYSA-N tri(propan-2-yl)-tri(propan-2-yl)silyloxysilane Chemical compound CC(C)[Si](C(C)C)(C(C)C)O[Si](C(C)C)(C(C)C)C(C)C LGSAOJLQTXCYHF-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Endocrinology (AREA)
Dermatology (AREA)
Reproductive Health (AREA)
Urology & Nephrology (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Pain & Pain Management (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Immunology (AREA)
Gynecology & Obstetrics (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK894-96A 1994-01-25 1995-01-23 Bicyclic compounds, pharmaceutical compositions on their base and preventing method of blastocyst implantation SK89496A3 (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US18673594A	1994-01-25	1994-01-25
US18674594A	1994-01-25	1994-01-25
US08/358,351 US5654307A (en)	1994-01-25	1994-12-23	Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family
PCT/US1995/000941 WO1995019774A1 (en)	1994-01-25	1995-01-23	Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family

Publications (1)

Publication Number	Publication Date
SK89496A3 true SK89496A3 (en)	1997-10-08

Family

ID=27392143

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK894-96A SK89496A3 (en)	1994-01-25	1995-01-23	Bicyclic compounds, pharmaceutical compositions on their base and preventing method of blastocyst implantation

Country Status (21)

Country	Link
US (5)	US6084095A (cs)
EP (1)	EP0742717A1 (cs)
JP (1)	JPH09508127A (cs)
CN (2)	CN1493291A (cs)
AU (1)	AU686334B2 (cs)
BG (1)	BG63245B1 (cs)
CA (1)	CA2177372A1 (cs)
CZ (1)	CZ197096A3 (cs)
FI (3)	FI114213B (cs)
GE (1)	GEP20012376B (cs)
HR (1)	HRP950034A2 (cs)
HU (1)	HU221741B1 (cs)
IL (1)	IL112249A (cs)
MD (1)	MD1632G2 (cs)
NO (1)	NO309892B1 (cs)
NZ (1)	NZ281011A (cs)
PL (1)	PL179132B1 (cs)
RO (1)	RO117257B1 (cs)
SK (1)	SK89496A3 (cs)
TJ (1)	TJ381B (cs)
WO (1)	WO1995019774A1 (cs)

Families Citing this family (496)

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Publication number	Priority date	Publication date	Assignee	Title
US7772432B2 (en)	1991-09-19	2010-08-10	Astrazeneca Ab	Amidobenzamide derivatives which are useful as cytokine inhibitors
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1995
- 1995-01-04 IL IL11224995A patent/IL112249A/en not_active IP Right Cessation
- 1995-01-23 JP JP7519732A patent/JPH09508127A/ja not_active Ceased
- 1995-01-23 RO RO96-01517A patent/RO117257B1/ro unknown
- 1995-01-23 AU AU17314/95A patent/AU686334B2/en not_active Ceased
- 1995-01-23 NZ NZ281011A patent/NZ281011A/en unknown
- 1995-01-23 SK SK894-96A patent/SK89496A3/sk unknown
- 1995-01-23 CZ CZ961970A patent/CZ197096A3/cs unknown
- 1995-01-23 CA CA002177372A patent/CA2177372A1/en not_active Abandoned
- 1995-01-23 TJ TJ96000352A patent/TJ381B/xx unknown
- 1995-01-23 WO PCT/US1995/000941 patent/WO1995019774A1/en not_active Ceased
- 1995-01-23 HU HU9602017A patent/HU221741B1/hu not_active IP Right Cessation
- 1995-01-23 PL PL95315633A patent/PL179132B1/pl not_active IP Right Cessation
- 1995-01-23 GE GEAP19953313A patent/GEP20012376B/en unknown
- 1995-01-23 MD MD96-0217A patent/MD1632G2/ro not_active IP Right Cessation
- 1995-01-23 CN CNA031220355A patent/CN1493291A/zh active Pending
- 1995-01-23 CN CNB951913107A patent/CN1140269C/zh not_active Expired - Fee Related
- 1995-01-23 EP EP95909316A patent/EP0742717A1/en not_active Withdrawn
- 1995-01-24 HR HR08/358,351A patent/HRP950034A2/hr not_active Application Discontinuation
1996
- 1996-05-20 BG BG100614A patent/BG63245B1/bg unknown
- 1996-07-15 FI FI962856A patent/FI114213B/fi active IP Right Grant
- 1996-07-24 NO NO963094A patent/NO309892B1/no unknown
1997
- 1997-03-06 US US08/811,797 patent/US6084095A/en not_active Expired - Fee Related
1998
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- 1998-11-13 US US09/191,163 patent/US6265410B1/en not_active Expired - Fee Related
2001
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2002
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2004
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- 2004-05-07 FI FI20040648A patent/FI20040648A7/fi not_active Application Discontinuation

Also Published As

Publication number	Publication date
FI114213B (fi)	2004-09-15
TJ381B (en)	2004-04-16
RO117257B1 (ro)	2001-12-28
US6455534B2 (en)	2002-09-24
FI20040648A7 (fi)	2004-05-07
BG63245B1 (bg)	2001-07-31
HRP950034A2 (en)	1997-10-31
CZ197096A3 (en)	1997-09-17
JPH09508127A (ja)	1997-08-19
MD1632F2 (en)	2001-03-31
IL112249A0 (en)	1995-03-30
PL179132B1 (pl)	2000-07-31
NO309892B1 (no)	2001-04-17
HU221741B1 (hu)	2002-12-28
US20030186987A1 (en)	2003-10-02
FI962856L (fi)	1996-09-25
MD1632G2 (ro)	2001-12-31
NO963094D0 (no)	1996-07-24
CN1140269C (zh)	2004-03-03
IL112249A (en)	2001-11-25
US6713484B2 (en)	2004-03-30
US6265410B1 (en)	2001-07-24
CN1139383A (zh)	1997-01-01
FI20040649A7 (fi)	2004-05-07
AU1731495A (en)	1995-08-08
HU9602017D0 (en)	1996-09-30
US20010027197A1 (en)	2001-10-04
MD960217A (en)	1998-04-30
US6084095A (en)	2000-07-04
HUT74589A (en)	1997-01-28
PL315633A1 (en)	1996-11-25
AU686334B2 (en)	1998-02-05
US6521620B1 (en)	2003-02-18
NO963094L (no)	1996-07-24
NZ281011A (en)	2002-02-01
FI962856A0 (fi)	1996-07-15
GEP20012376B (en)	2001-03-25
CA2177372A1 (en)	1995-07-27
BG100614A (bg)	1997-03-31
CN1493291A (zh)	2004-05-05
WO1995019774A1 (en)	1995-07-27
EP0742717A1 (en)	1996-11-20

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