FI112079B - 2-(2-amino-4-okso-tetrahydropyrido[2,3-d]-pyridiini- ja pyrimido[5,4-b][1,4]tiatsin-6-yyli)etyyli-4-metyylitien-2-yyli-L-glutamiinihappojohdannaisia - Google Patents

2-(2-amino-4-okso-tetrahydropyrido[2,3-d]-pyridiini- ja pyrimido[5,4-b][1,4]tiatsin-6-yyli)etyyli-4-metyylitien-2-yyli-L-glutamiinihappojohdannaisia Download PDF

Info

Publication number: FI112079B
Authority: FI; Finland
Prior art keywords: compound; ethyl; oxo; formula; amino
Prior art date: 1994-07-28

Application number

FI970317A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI970317A (fi

FI970317A0 (fi

Inventor

Michael D Varney

William H Romines

Original Assignee

Agouron Pharma

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.)

1994-07-28

Filing date

1997-01-24

Publication date

2003-10-31

1997-01-24 Application filed by Agouron Pharma filed Critical Agouron Pharma

1997-01-24 Publication of FI970317A0 publication Critical patent/FI970317A0/fi

1997-03-05 Publication of FI970317A publication Critical patent/FI970317A/fi

2003-10-31 Application granted granted Critical

2003-10-31 Publication of FI112079B publication Critical patent/FI112079B/fi

Links

-1 2-Amino-4-oxo-tetrahydropyrido [2,3-d] -pyridin Chemical compound 0.000 title claims description 26
229960002989 glutamic acid Drugs 0.000 title claims description 11
150000001875 compounds Chemical class 0.000 claims abstract description 130
238000000034 method Methods 0.000 claims abstract description 20
150000003839 salts Chemical class 0.000 claims abstract description 16
230000001028 anti-proliverative effect Effects 0.000 claims abstract description 11
239000000203 mixture Substances 0.000 claims abstract description 10
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 19
229910052717 sulfur Inorganic materials 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
230000012010 growth Effects 0.000 claims description 10
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
244000005700 microbiome Species 0.000 claims description 5
239000011593 sulfur Substances 0.000 claims description 5
229940079593 drug Drugs 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
241000277284 Salvelinus fontinalis Species 0.000 claims 1
ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims 1
230000035897 transcription Effects 0.000 claims 1
238000013518 transcription Methods 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 abstract description 15
239000000543 intermediate Substances 0.000 abstract description 9
239000003944 phosphoribosylglycinamide formyltransferase inhibitor Substances 0.000 abstract description 9
230000015572 biosynthetic process Effects 0.000 abstract description 3
230000003389 potentiating effect Effects 0.000 abstract description 3
238000003786 synthesis reaction Methods 0.000 abstract description 3
OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 34
239000011724 folic acid Substances 0.000 description 30
210000004027 cell Anatomy 0.000 description 28
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
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239000000047 product Substances 0.000 description 23
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000002904 solvent Substances 0.000 description 18
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239000002585 base Substances 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
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229940049906 glutamate Drugs 0.000 description 14
238000004458 analytical method Methods 0.000 description 13
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
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230000005764 inhibitory process Effects 0.000 description 11
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
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DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
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XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
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YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
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239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000011734 sodium Substances 0.000 description 6
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000000872 buffer Substances 0.000 description 5
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241000400611 Eucalyptus deanei Species 0.000 description 4
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
239000002168 alkylating agent Substances 0.000 description 4
229940100198 alkylating agent Drugs 0.000 description 4
230000003432 anti-folate effect Effects 0.000 description 4
229940127074 antifolate Drugs 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
229940125904 compound 1 Drugs 0.000 description 4
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QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
235000018102 proteins Nutrition 0.000 description 4
102000004169 proteins and genes Human genes 0.000 description 4
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BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 4
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 4
HSHPZFSEXMTXSY-UHFFFAOYSA-N 5-bromo-4-methylthiophene-2-carboxylic acid Chemical compound CC=1C=C(C(O)=O)SC=1Br HSHPZFSEXMTXSY-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 3
235000019502 Orange oil Nutrition 0.000 description 3
230000001476 alcoholic effect Effects 0.000 description 3
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229910052794 bromium Inorganic materials 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
210000000170 cell membrane Anatomy 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
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QEUBTYRTXLRKKN-UHFFFAOYSA-N methyl 4-methyl-5-(3-oxopropyl)thiophene-2-carboxylate Chemical compound COC(=O)C1=CC(C)=C(CCC=O)S1 QEUBTYRTXLRKKN-UHFFFAOYSA-N 0.000 description 3
JUMDSAWWVCBSNK-UHFFFAOYSA-N methyl 5-(3-hydroxypropyl)-4-methylthiophene-2-carboxylate Chemical compound COC(=O)C1=CC(C)=C(CCCO)S1 JUMDSAWWVCBSNK-UHFFFAOYSA-N 0.000 description 3
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230000001988 toxicity Effects 0.000 description 3
125000004665 trialkylsilyl group Chemical group 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
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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 description 2
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CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
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CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
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230000003213 activating effect Effects 0.000 description 2
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125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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LXNIFSQVULLYIY-UHFFFAOYSA-N methyl 5-(3-hydroxyprop-1-ynyl)-4-methylthiophene-2-carboxylate Chemical compound COC(=O)C1=CC(C)=C(C#CCO)S1 LXNIFSQVULLYIY-UHFFFAOYSA-N 0.000 description 2
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NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
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KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 2
239000000376 reactant Substances 0.000 description 2
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229910052708 sodium Inorganic materials 0.000 description 2
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GUUBJKMBDULZTE-UHFFFAOYSA-M potassium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[K+].OCCN1CCN(CCS(O)(=O)=O)CC1 GUUBJKMBDULZTE-UHFFFAOYSA-M 0.000 description 1
239000002243 precursor Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
DGMKFQYCZXERLX-UHFFFAOYSA-N proglumide Chemical compound CCCN(CCC)C(=O)C(CCC(O)=O)NC(=O)C1=CC=CC=C1 DGMKFQYCZXERLX-UHFFFAOYSA-N 0.000 description 1
229960003857 proglumide Drugs 0.000 description 1
TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
239000011535 reaction buffer Substances 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
239000002336 ribonucleotide Substances 0.000 description 1
125000002652 ribonucleotide group Chemical group 0.000 description 1
229910052711 selenium Inorganic materials 0.000 description 1
239000011669 selenium Substances 0.000 description 1
239000002002 slurry Substances 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
229960004306 sulfadiazine Drugs 0.000 description 1
229960004673 sulfadoxine Drugs 0.000 description 1
229960005404 sulfamethoxazole Drugs 0.000 description 1
GPTONYMQFTZPKC-UHFFFAOYSA-N sulfamethoxydiazine Chemical compound N1=CC(OC)=CN=C1NS(=O)(=O)C1=CC=C(N)C=C1 GPTONYMQFTZPKC-UHFFFAOYSA-N 0.000 description 1
229960002229 sulfametoxydiazine Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
150000003571 thiolactams Chemical class 0.000 description 1
238000004448 titration Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1
230000007723 transport mechanism Effects 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
229960001082 trimethoprim Drugs 0.000 description 1
NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
229960001099 trimetrexate Drugs 0.000 description 1
CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
210000003934 vacuole Anatomy 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
150000003722 vitamin derivatives Chemical class 0.000 description 1
238000010792 warming Methods 0.000 description 1

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
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- 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

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pyridine Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Electrochromic Elements, Electrophoresis, Or Variable Reflection Or Absorption Elements (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

FI970317A 1994-07-28 1997-01-24 2-(2-amino-4-okso-tetrahydropyrido[2,3-d]-pyridiini- ja pyrimido[5,4-b][1,4]tiatsin-6-yyli)etyyli-4-metyylitien-2-yyli-L-glutamiinihappojohdannaisia FI112079B (fi)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US08/281,639 US5608082A (en)	1994-07-28	1994-07-28	Compounds useful as antiproliferative agents and GARFT inhibitors
US28163994		1994-07-28
US9509519		1995-07-28
PCT/US1995/009519 WO1996003406A1 (en)	1994-07-28	1995-07-28	Compounds useful as antiproliferative agents and garft inhibitors

Publications (3)

Publication Number	Publication Date
FI970317A0 FI970317A0 (fi)	1997-01-24
FI970317A FI970317A (fi)	1997-03-05
FI112079B true FI112079B (fi)	2003-10-31

Family

ID=23078167

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI970317A FI112079B (fi)	1994-07-28	1997-01-24	2-(2-amino-4-okso-tetrahydropyrido[2,3-d]-pyridiini- ja pyrimido[5,4-b][1,4]tiatsin-6-yyli)etyyli-4-metyylitien-2-yyli-L-glutamiinihappojohdannaisia

Country Status (20)

Country	Link
US (2)	US5608082A (zh)
EP (1)	EP0773943B1 (zh)
JP (1)	JPH10503762A (zh)
KR (1)	KR100380610B1 (zh)
CN (2)	CN1091770C (zh)
AT (1)	ATE206122T1 (zh)
AU (1)	AU697138B2 (zh)
CA (1)	CA2195420A1 (zh)
DE (1)	DE69522945T2 (zh)
DK (1)	DK0773943T3 (zh)
ES (1)	ES2162933T3 (zh)
FI (1)	FI112079B (zh)
MX (1)	MX9700675A (zh)
NO (1)	NO308248B1 (zh)
NZ (1)	NZ290703A (zh)
PT (1)	PT773943E (zh)
RU (1)	RU2152945C2 (zh)
SI (1)	SI0773943T1 (zh)
TW (1)	TW432062B (zh)
WO (1)	WO1996003406A1 (zh)

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WO2003033477A1 (en) *	2001-10-12	2003-04-24	Warner-Lambert Company Llc	Alkynlated fused ring pyrimidine compounds as matrix metalloprotease-13 inhibitor
JP4164028B2 (ja)	2001-10-12	2008-10-08	ワーナー−ランバートカンパニーリミテッドライアビリティーカンパニー	アルキンマトリックスメタロプロテイナーゼ阻害剤
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US6962922B2 (en) *	2001-10-12	2005-11-08	Warner-Lambert Company Llc	Alkynylated quinazoline compounds
US20040043959A1 (en) *	2002-03-04	2004-03-04	Bloom Laura A.	Combination therapies for treating methylthioadenosine phosphorylase deficient cells
US6894057B2 (en) *	2002-03-08	2005-05-17	Warner-Lambert Company	Oxo-azabicyclic compounds
US6747147B2 (en)	2002-03-08	2004-06-08	Warner-Lambert Company	Oxo-azabicyclic compounds
US20040006077A1 (en) *	2002-06-25	2004-01-08	Bernard Gaudilliere	Thiazine and oxazine derivatives as MMP-13 inhibitors
EP1534274A1 (en) *	2002-07-17	2005-06-01	Warner-Lambert Company LLC	Combination of an allosteric alkyne inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib
WO2004113337A1 (en) *	2003-06-25	2004-12-29	Pfizer Inc.	Convergent synthesis of a garft inhibitor containing a methyl substitute thiophene core and a tetrahydropyrido`2,3-d! pyrimidine ring system and intermediates therefor
WO2004113328A1 (en) *	2003-06-25	2004-12-29	Pfizer Inc.	Convergent asymmetric synthesis route to produce a key intermediate towards the synthesis of a garft inhibitor
WO2005016926A1 (en) *	2003-08-19	2005-02-24	Warner-Lambert Company Llc	Pyrido [3,4-d] pyrimidine derivatives as matrix metalloproteinase-13 inhibitors
US7420059B2 (en) *	2003-11-20	2008-09-02	Bristol-Myers Squibb Company	HMG-CoA reductase inhibitors and method
EA012970B1 (ru)	2005-04-26	2010-02-26	Пфайзер Инк.	Антитела против р-кадгерина
JP5161777B2 (ja)	2005-09-07	2013-03-13	アムジェンフレモントインク．	アクチビン受容体様キナーゼ−１に対するヒトモノクローナル抗体
EP2258700A1 (en)	2006-05-09	2010-12-08	Pfizer Products Inc.	Cycloalkylamino acid derivatives and pharmaceutical compositions thereof
US8252804B2 (en) *	2008-10-01	2012-08-28	Duquesne University Of The Holy Spirit	Selective proton coupled folate transporter and folate receptor, and GARFTase inhibitor compounds and methods of using the same
PH12013501727A1 (en)	2011-02-23	2013-10-07	Lupin Ltd	Heteroaryl derivatives as alpha7 nachr modulators
GB201103578D0 (en)	2011-03-02	2011-04-13	Sabrepharm Ltd	Dipyridinium derivatives
ES2606043T3 (es)	2011-07-05	2017-03-17	Lupin Limited	Derivados de biarilo como moduladores de nAChR
CN103958457A (zh) *	2011-09-29	2014-07-30	埃莫里大学	鞘氨醇类似物、组合物及其相关方法
WO2013132380A1 (en)	2012-03-06	2013-09-12	Lupin Limited	Thiazole derivatives as alpha 7 nachr modulators
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CN115634228B (zh) *	2021-07-20	2024-03-19	首都医科大学	嘌呤合成抑制剂在制备治疗缺血和缺血再灌注损伤药物中的应用

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US4889859A (en) *	1988-02-05	1989-12-26	The Trustees Of Princeton University	Pyrido[2,3-d]pyrimidine derivatives
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US4882333A (en) *	1988-05-25	1989-11-21	The Trustess Of Princeton University	N-(5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl-alkanoyl)-glutamic acid derivatives
DK172753B1 (da) *	1988-05-25	1999-06-28	Lilly Co Eli	N-(5,6,7,8-tetrahydropyrido[2,3--d]pyrimidin-6-yl-alkanoyl)-glutaminsyrederivater, deres anvendelse, farmaceutiske præparat
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US4883799A (en) *	1988-06-29	1989-11-28	The Trustees Of Princeton University	N-(4-(1-hydroxy-3-(5,6,7,8-tetrahydropyrido(2,3,-d)-pyrimidin-6-yl)prop-2-yl)benzoyl)glutamic acid derivatives
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1994
- 1994-07-28 US US08/281,639 patent/US5608082A/en not_active Expired - Fee Related
1995
- 1995-06-06 US US08/467,945 patent/US5646141A/en not_active Expired - Fee Related
- 1995-07-28 RU RU97103518/04A patent/RU2152945C2/ru not_active IP Right Cessation
- 1995-07-28 PT PT95927503T patent/PT773943E/pt unknown
- 1995-07-28 ES ES95927503T patent/ES2162933T3/es not_active Expired - Lifetime
- 1995-07-28 EP EP95927503A patent/EP0773943B1/en not_active Expired - Lifetime
- 1995-07-28 KR KR1019970700588A patent/KR100380610B1/ko not_active IP Right Cessation
- 1995-07-28 CA CA002195420A patent/CA2195420A1/en not_active Abandoned
- 1995-07-28 MX MX9700675A patent/MX9700675A/es not_active IP Right Cessation
- 1995-07-28 CN CN95194376A patent/CN1091770C/zh not_active Expired - Fee Related
- 1995-07-28 SI SI9530534T patent/SI0773943T1/xx unknown
- 1995-07-28 DE DE69522945T patent/DE69522945T2/de not_active Expired - Fee Related
- 1995-07-28 WO PCT/US1995/009519 patent/WO1996003406A1/en active IP Right Grant
- 1995-07-28 AT AT95927503T patent/ATE206122T1/de not_active IP Right Cessation
- 1995-07-28 AU AU31517/95A patent/AU697138B2/en not_active Ceased
- 1995-07-28 JP JP8505975A patent/JPH10503762A/ja not_active Withdrawn
- 1995-07-28 NZ NZ290703A patent/NZ290703A/en unknown
- 1995-07-28 DK DK95927503T patent/DK0773943T3/da active
1996
- 1996-01-29 TW TW085101051A patent/TW432062B/zh not_active IP Right Cessation
1997
- 1997-01-24 FI FI970317A patent/FI112079B/fi not_active IP Right Cessation
- 1997-01-27 NO NO970349A patent/NO308248B1/no not_active IP Right Cessation
2001
- 2001-12-05 CN CN01142735A patent/CN1394857A/zh active Pending

Also Published As

Publication number	Publication date
AU3151795A (en)	1996-02-22
PT773943E (pt)	2002-01-30
FI970317A (fi)	1997-03-05
EP0773943B1 (en)	2001-09-26
KR100380610B1 (ko)	2003-08-27
ES2162933T3 (es)	2002-01-16
SI0773943T1 (en)	2001-12-31
CA2195420A1 (en)	1996-02-08
DK0773943T3 (da)	2002-03-04
RU2152945C2 (ru)	2000-07-20
WO1996003406A1 (en)	1996-02-08
US5608082A (en)	1997-03-04
CN1154110A (zh)	1997-07-09
ATE206122T1 (de)	2001-10-15
US5646141A (en)	1997-07-08
NO970349L (no)	1997-03-12
NO970349D0 (no)	1997-01-27
NZ290703A (en)	1998-11-25
CN1091770C (zh)	2002-10-02
NO308248B1 (no)	2000-08-21
EP0773943A1 (en)	1997-05-21
AU697138B2 (en)	1998-09-24
MX9700675A (es)	1997-04-30
FI970317A0 (fi)	1997-01-24
TW432062B (en)	2001-05-01
DE69522945D1 (de)	2001-10-31
JPH10503762A (ja)	1998-04-07
CN1394857A (zh)	2003-02-05
DE69522945T2 (de)	2002-03-28

Publication	Publication Date	Title
FI112079B (fi)	2003-10-31	2-(2-amino-4-okso-tetrahydropyrido[2,3-d]-pyridiini- ja pyrimido[5,4-b][1,4]tiatsin-6-yyli)etyyli-4-metyylitien-2-yyli-L-glutamiinihappojohdannaisia
KR910001136B1 (ko)	1991-02-25	축합 이미다조피리딘 유도체의 제조방법
EP1399444B1 (fr)	2007-04-11	Composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens
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