HRP970391A2 - Phosphinate based inhibitors of matrix metalloproteases - Google Patents

Phosphinate based inhibitors of matrix metalloproteases

Info

Publication number: HRP970391A2
Authority: HR; Croatia
Prior art keywords: alkyl; methylcarbamoyl; phosphinic acid; dimethyl; benzyl
Prior art date: 1996-07-18

Application number

HR60/021,959A

Other languages

English (en)

Croatian (hr)

Inventor

Lawrence Alan Reiter

Original Assignee

Lawrence Alan Reiter

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.)

1996-07-18

Filing date

1997-07-17

Publication date

1998-08-31

1997-07-17 Application filed by Lawrence Alan Reiter filed Critical Lawrence Alan Reiter

1998-08-31 Publication of HRP970391A2 publication Critical patent/HRP970391A2/hr

Links

239000003112 inhibitor Substances 0.000 title description 17
239000011159 matrix material Substances 0.000 title description 3
102000005741 Metalloproteases Human genes 0.000 title description 2
108010006035 Metalloproteases Proteins 0.000 title description 2
ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 72
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 37
108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 27
102000003390 tumor necrosis factor Human genes 0.000 claims description 27
-1 hydroxy, amino Chemical group 0.000 claims description 25
238000000034 method Methods 0.000 claims description 19
230000005764 inhibitory process Effects 0.000 claims description 16
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 14
108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 14
125000006719 (C6-C10) aryl (C1-C6) alkyl group Chemical group 0.000 claims description 13
201000010099 disease Diseases 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 13
241000124008 Mammalia Species 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 10
229910052799 carbon Inorganic materials 0.000 claims description 9
230000000694 effects Effects 0.000 claims description 9
238000011282 treatment Methods 0.000 claims description 9
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 8
KATBPZLMXQIZLF-UHFFFAOYSA-N (4-benzylphenyl)methyl-[2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-4-methylpentyl]phosphinic acid Chemical compound C1=CC(CP(O)(=O)CC(CC(C)C)C(=O)NC(C(=O)NC)C(C)(C)C)=CC=C1CC1=CC=CC=C1 KATBPZLMXQIZLF-UHFFFAOYSA-N 0.000 claims description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
206010028980 Neoplasm Diseases 0.000 claims description 7
208000025865 Ulcer Diseases 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
230000036269 ulceration Effects 0.000 claims description 7
206010040047 Sepsis Diseases 0.000 claims description 6
206010040070 Septic Shock Diseases 0.000 claims description 6
206010003246 arthritis Diseases 0.000 claims description 6
201000011510 cancer Diseases 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
208000028169 periodontal disease Diseases 0.000 claims description 6
230000036303 septic shock Effects 0.000 claims description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 5
208000030507 AIDS Diseases 0.000 claims description 5
206010014989 Epidermolysis bullosa Diseases 0.000 claims description 5
206010039705 Scleritis Diseases 0.000 claims description 5
229940035676 analgesics Drugs 0.000 claims description 5
239000000730 antalgic agent Substances 0.000 claims description 5
125000004104 aryloxy group Chemical group 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
231100000433 cytotoxic Toxicity 0.000 claims description 5
230000001472 cytotoxic effect Effects 0.000 claims description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
208000037803 restenosis Diseases 0.000 claims description 5
125000001544 thienyl group Chemical group 0.000 claims description 5
125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 4
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 4
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 4
229910005965 SO 2 Inorganic materials 0.000 claims description 4
239000002246 antineoplastic agent Substances 0.000 claims description 4
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 4
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
208000002780 macular degeneration Diseases 0.000 claims description 4
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 4
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 3
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 3
239000000825 pharmaceutical preparation Substances 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
LQDHQVJPGDBOJR-UHFFFAOYSA-N (4-benzylphenyl)methyl-[2-(cyclohexylmethyl)-3-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-3-oxopropyl]phosphinic acid Chemical compound C=1C=C(CC=2C=CC=CC=2)C=CC=1CP(O)(=O)CC(C(=O)NC(C(=O)NC)C(C)(C)C)CC1CCCCC1 LQDHQVJPGDBOJR-UHFFFAOYSA-N 0.000 claims description 2
UTSFQPTVPZNJJH-UHFFFAOYSA-N (4-benzylphenyl)methyl-[2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-4-phenylbutyl]phosphinic acid Chemical compound C=1C=C(CC=2C=CC=CC=2)C=CC=1CP(O)(=O)CC(C(=O)NC(C(=O)NC)C(C)(C)C)CCC1=CC=CC=C1 UTSFQPTVPZNJJH-UHFFFAOYSA-N 0.000 claims description 2
IHXYDMMVEDLUPK-UHFFFAOYSA-N (4-benzylphenyl)methyl-[2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-5,5,5-trifluoropentyl]phosphinic acid Chemical compound C1=CC(CP(O)(=O)CC(CCC(F)(F)F)C(=O)NC(C(=O)NC)C(C)(C)C)=CC=C1CC1=CC=CC=C1 IHXYDMMVEDLUPK-UHFFFAOYSA-N 0.000 claims description 2
XCUQHJJAOKKHJS-UHFFFAOYSA-N (4-benzylphenyl)methyl-[2-[[3-(4-methoxyphenyl)-1-(methylamino)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]phosphinic acid Chemical compound C=1C=C(CC=2C=CC=CC=2)C=CC=1CP(O)(=O)CC(CC(C)C)C(=O)NC(C(=O)NC)CC1=CC=C(OC)C=C1 XCUQHJJAOKKHJS-UHFFFAOYSA-N 0.000 claims description 2
NQECQHIRGFLISY-UHFFFAOYSA-N (4-benzylphenyl)methyl-[2-[[3-(4-methoxyphenyl)-1-(methylamino)-1-oxopropan-2-yl]carbamoyl]-6-phenoxyhexyl]phosphinic acid Chemical compound C=1C=CC=CC=1OCCCCC(CP(O)(=O)CC=1C=CC(CC=2C=CC=CC=2)=CC=1)C(=O)NC(C(=O)NC)CC1=CC=C(OC)C=C1 NQECQHIRGFLISY-UHFFFAOYSA-N 0.000 claims description 2
JAAFICSMUDJNQS-UHFFFAOYSA-N (5-benzylpyridin-2-yl)methyl-[2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-4-methylpentyl]phosphinic acid Chemical compound C1=NC(CP(O)(=O)CC(CC(C)C)C(=O)NC(C(=O)NC)C(C)(C)C)=CC=C1CC1=CC=CC=C1 JAAFICSMUDJNQS-UHFFFAOYSA-N 0.000 claims description 2
KVOARZLBLIHNAH-UHFFFAOYSA-N (5-benzylthiophen-2-yl)methyl-[2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-4-methylpentyl]phosphinic acid Chemical compound S1C(CP(O)(=O)CC(CC(C)C)C(=O)NC(C(=O)NC)C(C)(C)C)=CC=C1CC1=CC=CC=C1 KVOARZLBLIHNAH-UHFFFAOYSA-N 0.000 claims description 2
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
TTZWROSODOHYKZ-UHFFFAOYSA-N [2-(cyclobutylmethyl)-3-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-3-oxopropyl]-[[4-[(2-fluorophenyl)methyl]phenyl]methyl]phosphinic acid Chemical compound C=1C=C(CC=2C(=CC=CC=2)F)C=CC=1CP(O)(=O)CC(C(=O)NC(C(=O)NC)C(C)(C)C)CC1CCC1 TTZWROSODOHYKZ-UHFFFAOYSA-N 0.000 claims description 2
LKOQZTZLLAIOGB-UHFFFAOYSA-N [2-(cyclopropylmethyl)-3-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-3-oxopropyl]-[[4-[(2-fluorophenyl)methyl]phenyl]methyl]phosphinic acid Chemical compound C=1C=C(CC=2C(=CC=CC=2)F)C=CC=1CP(O)(=O)CC(C(=O)NC(C(=O)NC)C(C)(C)C)CC1CC1 LKOQZTZLLAIOGB-UHFFFAOYSA-N 0.000 claims description 2
YLNWMQOPZKKAIQ-UHFFFAOYSA-N [2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-4-methylpentyl]-[[4-(2-methylpropyl)phenyl]methyl]phosphinic acid Chemical compound CNC(=O)C(C(C)(C)C)NC(=O)C(CC(C)C)CP(O)(=O)CC1=CC=C(CC(C)C)C=C1 YLNWMQOPZKKAIQ-UHFFFAOYSA-N 0.000 claims description 2
VNYKUPXVMBIHEO-UHFFFAOYSA-N [2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-4-methylpentyl]-[[4-[(3-fluorophenyl)methyl]phenyl]methyl]phosphinic acid Chemical compound C1=CC(CP(O)(=O)CC(CC(C)C)C(=O)NC(C(=O)NC)C(C)(C)C)=CC=C1CC1=CC=CC(F)=C1 VNYKUPXVMBIHEO-UHFFFAOYSA-N 0.000 claims description 2
OWXGCYPTRHGHPT-UHFFFAOYSA-N [2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-4-methylpentyl]-[[4-[(4-fluorophenyl)methyl]phenyl]methyl]phosphinic acid Chemical compound C1=CC(CP(O)(=O)CC(CC(C)C)C(=O)NC(C(=O)NC)C(C)(C)C)=CC=C1CC1=CC=C(F)C=C1 OWXGCYPTRHGHPT-UHFFFAOYSA-N 0.000 claims description 2
YQHBOKCURQRVCG-UHFFFAOYSA-N [2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-5,5,5-trifluoropentyl]-[[4-[(2-fluorophenyl)methyl]phenyl]methyl]phosphinic acid Chemical compound C1=CC(CP(O)(=O)CC(CCC(F)(F)F)C(=O)NC(C(=O)NC)C(C)(C)C)=CC=C1CC1=CC=CC=C1F YQHBOKCURQRVCG-UHFFFAOYSA-N 0.000 claims description 2
BQHQFSSBHXZZQD-UHFFFAOYSA-N [4-(cyclohexylmethyl)phenyl]methyl-[2-[[3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]-4-methylpentyl]phosphinic acid Chemical compound C1=CC(CP(O)(=O)CC(CC(C)C)C(=O)NC(C(=O)NC)C(C)(C)C)=CC=C1CC1CCCCC1 BQHQFSSBHXZZQD-UHFFFAOYSA-N 0.000 claims description 2
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
VWYWYCIQBGGPKK-UHFFFAOYSA-N benzyl-[2-[[3-(4-methoxyphenyl)-1-(methylamino)-1-oxopropan-2-yl]carbamoyl]-6-phenoxyhexyl]phosphinic acid Chemical compound C=1C=CC=CC=1OCCCCC(CP(O)(=O)CC=1C=CC=CC=1)C(=O)NC(C(=O)NC)CC1=CC=C(OC)C=C1 VWYWYCIQBGGPKK-UHFFFAOYSA-N 0.000 claims description 2
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
150000001721 carbon Chemical group 0.000 claims description 2
125000004432 carbon atom Chemical group C* 0.000 claims description 2
229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims description 2
125000001786 isothiazolyl group Chemical group 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical compound C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
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125000004437 phosphorous atom Chemical group 0.000 claims description 2
229910052698 phosphorus Inorganic materials 0.000 claims description 2
125000003373 pyrazinyl group Chemical group 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
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102000029816 Collagenase Human genes 0.000 description 17
229960002424 collagenase Drugs 0.000 description 17
239000000243 solution Substances 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
239000000203 mixture Substances 0.000 description 14
239000000758 substrate Substances 0.000 description 14
229910052717 sulfur Inorganic materials 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
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238000006243 chemical reaction Methods 0.000 description 12
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239000011541 reaction mixture Substances 0.000 description 11
238000012360 testing method Methods 0.000 description 11
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239000007787 solid Substances 0.000 description 9
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 8
102000004190 Enzymes Human genes 0.000 description 7
108090000790 Enzymes Proteins 0.000 description 7
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SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 3
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238000007911 parenteral administration Methods 0.000 description 1
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BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
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NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
229960001790 sodium citrate Drugs 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
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238000007920 subcutaneous administration Methods 0.000 description 1
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125000001424 substituent group Chemical group 0.000 description 1
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125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent 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
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
229940063683 taxotere Drugs 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
DRDCQJADRSJFFD-UHFFFAOYSA-N tris-hydroxymethyl-methyl-ammonium Chemical class OC[N+](C)(CO)CO DRDCQJADRSJFFD-UHFFFAOYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
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Classifications

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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- C07F9/28—Phosphorus compounds with one or more P—C bonds
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/306—Arylalkanephosphinic acids, e.g. Ar-(CH2)n-P(=X)(R)(XH), (X = O,S, Se; n>=1)
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
- C—CHEMISTRY; METALLURGY
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65525—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a seven-(or more) membered ring
- C07F9/65527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a seven-(or more) membered ring condensed with carbocyclic rings or carbocyclic ring systems

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Chemical & Material Sciences (AREA)
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Biomedical Technology (AREA)
Neurology (AREA)
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Dermatology (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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HR60/021,959A 1996-07-18 1997-07-17 Phosphinate based inhibitors of matrix metalloproteases HRP970391A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US2195996P	1996-07-18	1996-07-18

Publications (1)

Publication Number	Publication Date
HRP970391A2 true HRP970391A2 (en)	1998-08-31

Family

ID=21807061

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR60/021,959A HRP970391A2 (en)	1996-07-18	1997-07-17	Phosphinate based inhibitors of matrix metalloproteases

Country Status (40)

Country	Link
US (1)	US6147061A (tr)
EP (1)	EP0923585B1 (tr)
JP (1)	JP3299975B2 (tr)
KR (1)	KR20000067904A (tr)
CN (1)	CN1225639A (tr)
AP (1)	AP761A (tr)
AR (1)	AR008260A1 (tr)
AT (1)	ATE217315T1 (tr)
AU (1)	AU712973B2 (tr)
BG (1)	BG103111A (tr)
BR (1)	BR9710381A (tr)
CA (1)	CA2260898C (tr)
CO (1)	CO4890852A1 (tr)
CZ (1)	CZ11899A3 (tr)
DE (1)	DE69712496T2 (tr)
DK (1)	DK0923585T3 (tr)
EA (1)	EA199900036A1 (tr)
ES (1)	ES2175415T3 (tr)
GT (1)	GT199700085A (tr)
HN (1)	HN1997000099A (tr)
HR (1)	HRP970391A2 (tr)
HU (1)	HUP9903014A3 (tr)
ID (1)	ID19443A (tr)
IL (1)	IL127567A0 (tr)
IS (1)	IS4928A (tr)
MA (1)	MA24270A1 (tr)
NO (1)	NO990184L (tr)
NZ (1)	NZ333303A (tr)
OA (1)	OA10956A (tr)
PA (1)	PA8433701A1 (tr)
PE (1)	PE88198A1 (tr)
PL (1)	PL331254A1 (tr)
PT (1)	PT923585E (tr)
SI (1)	SI0923585T1 (tr)
SK (1)	SK3799A3 (tr)
TN (1)	TNSN97122A1 (tr)
TR (1)	TR199900066T2 (tr)
WO (1)	WO1998003516A1 (tr)
YU (1)	YU1899A (tr)
ZA (1)	ZA976330B (tr)

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1997
- 1997-06-30 EP EP97926182A patent/EP0923585B1/en not_active Expired - Lifetime
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ATE217315T1 (de)	2002-05-15
HN1997000099A (es)	1997-12-28
NO990184L (no)	1999-03-15
AP761A (en)	1999-09-13
YU1899A (sh)	2000-03-21
PT923585E (pt)	2002-08-30
IL127567A0 (en)	1999-10-28
HUP9903014A2 (en)	2000-07-28
WO1998003516A1 (en)	1998-01-29
SK3799A3 (en)	2000-03-13
DK0923585T3 (da)	2002-07-01
ES2175415T3 (es)	2002-11-16
KR20000067904A (ko)	2000-11-25
PA8433701A1 (es)	1999-12-27
SI0923585T1 (en)	2002-08-31
CO4890852A1 (es)	2000-02-28
PL331254A1 (en)	1999-07-05
CA2260898C (en)	2002-05-14
BG103111A (en)	1999-11-30
CA2260898A1 (en)	1998-01-29
PE88198A1 (es)	1998-12-21
HUP9903014A3 (en)	2000-08-28
MA24270A1 (fr)	1998-04-01
GT199700085A (es)	1999-01-06
TNSN97122A1 (fr)	2005-03-15
BR9710381A (pt)	1999-08-17
EP0923585B1 (en)	2002-05-08
JP3299975B2 (ja)	2002-07-08
IS4928A (is)	1998-12-18
ZA976330B (en)	1999-01-19
JPH11514673A (ja)	1999-12-14
TR199900066T2 (tr)	1999-04-21
EP0923585A1 (en)	1999-06-23
EA199900036A1 (ru)	1999-06-24
ID19443A (id)	1998-07-09
CN1225639A (zh)	1999-08-11
NZ333303A (en)	2000-06-23
CZ11899A3 (cs)	1999-11-17
AU712973B2 (en)	1999-11-18
NO990184D0 (no)	1999-01-15
AR008260A1 (es)	1999-12-29
OA10956A (en)	2001-10-30
DE69712496T2 (de)	2002-08-29
US6147061A (en)	2000-11-14
AU3104297A (en)	1998-02-10
DE69712496D1 (de)	2002-06-13
AP9701043A0 (en)	1997-07-31

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