IL125048A - History of barbituric acid and pharmaceutical preparations containing them to inhibit the metropolitan matrix - Google Patents

History of barbituric acid and pharmaceutical preparations containing them to inhibit the metropolitan matrix

Info

Publication number: IL125048A
Authority: IL; Israel
Prior art keywords: group; compound; monocycle; acid; substituted
Prior art date: 1995-12-23

Application number

IL12504896A

Other languages

English (en)

Hebrew (he)

Other versions

IL125048A0 (en

Original Assignee

Roche Diagnostics Gmbh

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.)

1995-12-23

Filing date

1996-12-20

Publication date

2004-02-19

1996-12-20 Application filed by Roche Diagnostics Gmbh filed Critical Roche Diagnostics Gmbh

1999-01-26 Publication of IL125048A0 publication Critical patent/IL125048A0/xx

2004-02-19 Publication of IL125048A publication Critical patent/IL125048A/en

Links

239000011159 matrix material Substances 0.000 title claims description 9
102000005741 Metalloproteases Human genes 0.000 title claims description 7
108010006035 Metalloproteases Proteins 0.000 title claims description 7
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
230000002401 inhibitory effect Effects 0.000 title claims description 3
150000007656 barbituric acids Chemical class 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 71
-1 hydroxy, thio Chemical group 0.000 claims abstract description 54
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 27
229910052760 oxygen Inorganic materials 0.000 claims abstract description 26
239000001301 oxygen Substances 0.000 claims abstract description 25
125000000217 alkyl group Chemical group 0.000 claims abstract description 21
125000005842 heteroatom Chemical group 0.000 claims abstract description 21
239000001257 hydrogen Substances 0.000 claims abstract description 19
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 18
229920006395 saturated elastomer Polymers 0.000 claims abstract description 17
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
125000002252 acyl group Chemical group 0.000 claims abstract description 15
125000003118 aryl group Chemical group 0.000 claims abstract description 15
229910052736 halogen Inorganic materials 0.000 claims abstract description 15
150000002367 halogens Chemical class 0.000 claims abstract description 15
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 12
125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 9
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
239000005864 Sulphur Chemical group 0.000 claims abstract description 8
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 7
125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 7
125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 7
125000004450 alkenylene group Chemical group 0.000 claims abstract description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 6
125000002947 alkylene group Chemical group 0.000 claims abstract description 6
125000006365 alkylene oxy carbonyl group Chemical group 0.000 claims abstract description 6
125000004682 aminothiocarbonyl group Chemical group NC(=S)* 0.000 claims abstract description 6
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims abstract description 6
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 5
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 5
125000006361 alkylene amino carbonyl group Chemical group 0.000 claims abstract description 5
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
239000000651 prodrug Substances 0.000 claims abstract description 5
229940002612 prodrug Drugs 0.000 claims abstract description 5
125000005110 aryl thio group Chemical group 0.000 claims abstract description 4
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 4
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims abstract description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 3
125000001769 aryl amino group Chemical group 0.000 claims abstract description 3
125000005135 aryl sulfinyl group Chemical group 0.000 claims abstract description 3
125000004104 aryloxy group Chemical group 0.000 claims abstract description 3
125000005518 carboxamido group Chemical group 0.000 claims abstract description 3
125000004122 cyclic group Chemical group 0.000 claims abstract description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 3
239000002253 acid Substances 0.000 claims description 108
HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 69
125000004193 piperazinyl group Chemical group 0.000 claims description 29
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 21
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 19
239000004305 biphenyl Chemical group 0.000 claims description 19
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
238000000034 method Methods 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 18
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 16
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 16
229910052794 bromium Inorganic materials 0.000 claims description 16
125000003386 piperidinyl group Chemical group 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
235000010290 biphenyl Nutrition 0.000 claims description 10
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
229910052740 iodine Inorganic materials 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 5
125000001041 indolyl group Chemical group 0.000 claims description 5
239000011630 iodine Substances 0.000 claims description 5
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 4
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
229910006074 SO2NH2 Inorganic materials 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
230000005764 inhibitory process Effects 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
230000001575 pathological effect Effects 0.000 claims description 3
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
125000004670 alkyl amino thio carbonyl group Chemical group 0.000 claims description 2
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
230000000694 effects Effects 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 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
125000002757 morpholinyl group Chemical group 0.000 claims description 2
201000006417 multiple sclerosis Diseases 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
201000008482 osteoarthritis Diseases 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 claims description 2
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
239000003814 drug Substances 0.000 claims 9
125000003373 pyrazinyl group Chemical group 0.000 claims 3
LUYJKNJSNFJKPI-UHFFFAOYSA-N 5-[4-(4-nitrophenyl)piperazin-1-yl]-5-octyl-1,3-diazinane-2,4,6-trione Chemical compound C1CN(C=2C=CC(=CC=2)[N+]([O-])=O)CCN1C1(CCCCCCCC)C(=O)NC(=O)NC1=O LUYJKNJSNFJKPI-UHFFFAOYSA-N 0.000 claims 2
125000002883 imidazolyl group Chemical group 0.000 claims 2
125000005936 piperidyl group Chemical group 0.000 claims 2
DSPQQVKMIMDNOL-UHFFFAOYSA-N 5-[1-(2-hydroxyethyl)piperazin-2-yl]-5-octyl-1,3-diazinane-2,4,6-trione Chemical compound C1NCCN(CCO)C1C1(CCCCCCCC)C(=O)NC(=O)NC1=O DSPQQVKMIMDNOL-UHFFFAOYSA-N 0.000 claims 1
KBYREIKVHAUQAR-UHFFFAOYSA-N 5-decyl-5-[1-(2-hydroxyethyl)piperazin-2-yl]-1,3-diazinane-2,4,6-trione Chemical compound C1NCCN(CCO)C1C1(CCCCCCCCCC)C(=O)NC(=O)NC1=O KBYREIKVHAUQAR-UHFFFAOYSA-N 0.000 claims 1
101000998548 Yersinia ruckeri Alkaline proteinase inhibitor Proteins 0.000 claims 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000002541 furyl group Chemical group 0.000 claims 1
239000003475 metalloproteinase inhibitor Substances 0.000 claims 1
210000001616 monocyte Anatomy 0.000 claims 1
125000002098 pyridazinyl group Chemical group 0.000 claims 1
125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
125000004568 thiomorpholinyl group Chemical group 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 4
125000004685 alkoxythiocarbonyl group Chemical group 0.000 abstract description 2
125000003837 (C1-C20) alkyl group Chemical group 0.000 abstract 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 65
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
238000002360 preparation method Methods 0.000 description 56
239000000047 product Substances 0.000 description 56
239000007787 solid Substances 0.000 description 55
239000000203 mixture Substances 0.000 description 52
239000000243 solution Substances 0.000 description 50
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
239000002904 solvent Substances 0.000 description 36
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
238000003756 stirring Methods 0.000 description 26
239000000725 suspension Substances 0.000 description 25
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
239000011541 reaction mixture Substances 0.000 description 24
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 23
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
229910052938 sodium sulfate Inorganic materials 0.000 description 20
235000011152 sodium sulphate Nutrition 0.000 description 20
239000012074 organic phase Substances 0.000 description 19
239000004202 carbamide Substances 0.000 description 18
238000001914 filtration Methods 0.000 description 18
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 16
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
239000011734 sodium Substances 0.000 description 16
229910052708 sodium Inorganic materials 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
235000013877 carbamide Nutrition 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
239000000284 extract Substances 0.000 description 13
239000002244 precipitate Substances 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
239000008346 aqueous phase Substances 0.000 description 12
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 11
239000007864 aqueous solution Substances 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
238000010898 silica gel chromatography Methods 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 6
229940126062 Compound A Drugs 0.000 description 6
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000003112 inhibitor Substances 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 6
238000010992 reflux Methods 0.000 description 6
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 5
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000003208 petroleum Substances 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
239000000758 substrate Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
238000009835 boiling Methods 0.000 description 4
239000012267 brine Substances 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
VOYADQIFGGIKAT-UHFFFAOYSA-N 1,3-dibutyl-4-hydroxy-2,6-dioxopyrimidine-5-carboximidamide Chemical compound CCCCn1c(O)c(C(N)=N)c(=O)n(CCCC)c1=O VOYADQIFGGIKAT-UHFFFAOYSA-N 0.000 description 3
WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 3
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FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
LJXVFUNQCQOJJV-UHFFFAOYSA-N diethyl 2-bromo-2-phenylpropanedioate Chemical compound CCOC(=O)C(Br)(C(=O)OCC)C1=CC=CC=C1 LJXVFUNQCQOJJV-UHFFFAOYSA-N 0.000 description 1
SPLKINYGZAOTSM-UHFFFAOYSA-N diethyl 2-naphthalen-2-ylpropanedioate Chemical compound C1=CC=CC2=CC(C(C(=O)OCC)C(=O)OCC)=CC=C21 SPLKINYGZAOTSM-UHFFFAOYSA-N 0.000 description 1
HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
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150000002170 ethers Chemical class 0.000 description 1
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NSQBADKMIYCCSC-UHFFFAOYSA-N ethyl 2-(3-hydroxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(O)=C1 NSQBADKMIYCCSC-UHFFFAOYSA-N 0.000 description 1
PUIBRHJUTVHVPI-UHFFFAOYSA-N ethyl 2-(4-butoxyphenyl)acetate Chemical compound CCCCOC1=CC=C(CC(=O)OCC)C=C1 PUIBRHJUTVHVPI-UHFFFAOYSA-N 0.000 description 1
CPYLMUNOJSVCRZ-UHFFFAOYSA-N ethyl 2-(4-phenoxyphenyl)acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1OC1=CC=CC=C1 CPYLMUNOJSVCRZ-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
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108091007167 extracellular matrix enzymes Proteins 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000012634 fragment Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229910001385 heavy metal Inorganic materials 0.000 description 1
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
230000009545 invasion Effects 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
238000002955 isolation Methods 0.000 description 1
VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
OHZZTXYKLXZFSZ-UHFFFAOYSA-I manganese(3+) 5,10,15-tris(1-methylpyridin-1-ium-4-yl)-20-(1-methylpyridin-4-ylidene)porphyrin-22-ide pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Mn+3].C1=CN(C)C=CC1=C1C(C=C2)=NC2=C(C=2C=C[N+](C)=CC=2)C([N-]2)=CC=C2C(C=2C=C[N+](C)=CC=2)=C(C=C2)N=C2C(C=2C=C[N+](C)=CC=2)=C2N=C1C=C2 OHZZTXYKLXZFSZ-UHFFFAOYSA-I 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
229940080818 propionamide Drugs 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
229960001404 quinidine Drugs 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
WWYDYZMNFQIYPT-UHFFFAOYSA-N ru78191 Chemical compound OC(=O)C(C(O)=O)C1=CC=CC=C1 WWYDYZMNFQIYPT-UHFFFAOYSA-N 0.000 description 1
125000005624 silicic acid group Chemical class 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000003381 stabilizer 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
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical group O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
125000000565 sulfonamide group Chemical group 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229940116269 uric acid Drugs 0.000 description 1
235000019871 vegetable fat Nutrition 0.000 description 1
230000004572 zinc-binding Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/62—Barbituric acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/66—Thiobarbituric acids

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Oncology (AREA)
Pain & Pain Management (AREA)
Ophthalmology & Optometry (AREA)
Communicable Diseases (AREA)
Immunology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

IL12504896A 1995-12-23 1996-12-20 History of barbituric acid and pharmaceutical preparations containing them to inhibit the metropolitan matrix IL125048A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19548624A DE19548624A1 (de)	1995-12-23	1995-12-23	Neue Barbitursäure-Derivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
PCT/EP1996/005766 WO1997023465A1 (en)	1995-12-23	1996-12-20	New barbituric acid derivatives, processes for their production and pharmaceutical agents containing these compounds

Publications (2)

Publication Number	Publication Date
IL125048A0 IL125048A0 (en)	1999-01-26
IL125048A true IL125048A (en)	2004-02-19

Family

ID=7781338

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12504896A IL125048A (en)	1995-12-23	1996-12-20	History of barbituric acid and pharmaceutical preparations containing them to inhibit the metropolitan matrix

Country Status (22)

Country	Link
US (2)	US6110924A (pt)
EP (1)	EP0869947B1 (pt)
JP (1)	JP4198752B2 (pt)
KR (1)	KR100440035B1 (pt)
CN (1)	CN1318406C (pt)
AT (1)	ATE226575T1 (pt)
BR (1)	BR9612232A (pt)
CZ (1)	CZ292503B6 (pt)
DE (2)	DE19548624A1 (pt)
DK (1)	DK0869947T3 (pt)
ES (1)	ES2184903T3 (pt)
HU (1)	HUP9901065A3 (pt)
IL (1)	IL125048A (pt)
MX (1)	MX9805063A (pt)
NO (1)	NO311572B1 (pt)
NZ (1)	NZ325802A (pt)
PL (1)	PL190217B1 (pt)
PT (1)	PT869947E (pt)
RU (1)	RU2177475C2 (pt)
TW (1)	TW518324B (pt)
WO (1)	WO1997023465A1 (pt)
ZA (1)	ZA9610765B (pt)

Families Citing this family (22)

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Publication number	Priority date	Publication date	Assignee	Title
JP2002504916A (ja)	1997-06-21	2002-02-12	ロシュダイアグノスティクスゲゼルシャフトミットベシュレンクテルハフツング	抗転移及び抗腫瘍活性を有するバルビツール酸誘導体
DE19726427A1 (de) *	1997-06-23	1998-12-24	Boehringer Mannheim Gmbh	Pyrimidin-2,4,6-trion-Derivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
US6350786B1 (en)	1998-09-22	2002-02-26	Hoffmann-La Roche Inc.	Stable complexes of poorly soluble compounds in ionic polymers
US6265578B1 (en)	1999-02-12	2001-07-24	Hoffmann-La Roche Inc.	Pyrimidine-2,4,6-triones
CO5210860A1 (es) *	1999-10-01	2002-10-30	Hoffmann La Roche	Nuevos derivados de pirimidina-2,4,6-triona
KR20030061825A (ko)	2000-10-26	2003-07-22	화이자 프로덕츠 인크.	피리미딘-2,4,6-트리온 메탈로프로테이나제 억제제
US6716845B2 (en) *	2001-03-30	2004-04-06	Hoffmann-La Roche Inc.	Barbituric acid derivatives
WO2002089824A1 (en) *	2001-05-03	2002-11-14	F. Hoffmann-La Roche Ag	Combination of a gelatinase inhibitor and an anti-tumor agent, and uses thereof
CA2446356C (en)	2001-05-09	2012-07-10	The Regents Of The University Of Michigan	Use of compositions for treating rosacea
WO2003053940A1 (en) *	2001-12-20	2003-07-03	Bristol-Myers Squibb Company	Barbituric acid derivatives as inhibitors of tnf-$g(a) converting enzyme (tace) and/or matrix metalloproteinases
NI200300045A (es) *	2002-04-26	2005-07-08	Pfizer Prod Inc	Inhibidores de triariloxiariloxipirimidin-2,4,6-triona de metaloproteinasa.
EP2181704B1 (en)	2002-12-30	2015-05-06	Angiotech International Ag	Drug delivery from rapid gelling polymer composition
WO2004084903A1 (en) *	2003-03-27	2004-10-07	F. Hoffmann-La Roche Ag	Use of a trioxopyrimidine for the treatment and prevention of ocular pathologic angiogenesis
WO2004084902A1 (en) *	2003-03-28	2004-10-07	F. Hoffmann-La Roche Ag	Use of a trioxopyrimidine for the treatment of chronic wounds
WO2004110457A1 (en) *	2003-06-06	2004-12-23	F. Hoffmann-La Roche Ag	Matrix metalloproteinases inhibitors for the stimulation and protection of bone marrow stem cells
DE602005008418D1 (de) *	2004-04-01	2008-09-04	Hoffmann La Roche	Verwendung von trioxopyrimidin zur behandlung und prävention von entzündlichen erkrankungen der bronchien
EP1735007A2 (en) *	2004-04-01	2006-12-27	F.Hoffmann-La Roche Ag	Cyclodextrin inclusion complexes of pyrimidine-2,4,6-triones
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1995
- 1995-12-23 DE DE19548624A patent/DE19548624A1/de not_active Withdrawn
1996
- 1996-12-20 ZA ZA9610765A patent/ZA9610765B/xx unknown
- 1996-12-20 HU HU9901065A patent/HUP9901065A3/hu unknown
- 1996-12-20 PL PL96327466A patent/PL190217B1/pl not_active IP Right Cessation
- 1996-12-20 ES ES96944612T patent/ES2184903T3/es not_active Expired - Lifetime
- 1996-12-20 CN CNB961800275A patent/CN1318406C/zh not_active Expired - Fee Related
- 1996-12-20 JP JP52331897A patent/JP4198752B2/ja not_active Expired - Fee Related
- 1996-12-20 RU RU98113916/04A patent/RU2177475C2/ru not_active IP Right Cessation
- 1996-12-20 DE DE69624500T patent/DE69624500T2/de not_active Expired - Fee Related
- 1996-12-20 BR BR9612232A patent/BR9612232A/pt not_active IP Right Cessation
- 1996-12-20 NZ NZ325802A patent/NZ325802A/xx unknown
- 1996-12-20 US US09/091,352 patent/US6110924A/en not_active Expired - Fee Related
- 1996-12-20 KR KR10-1998-0704855A patent/KR100440035B1/ko not_active IP Right Cessation
- 1996-12-20 WO PCT/EP1996/005766 patent/WO1997023465A1/en active IP Right Grant
- 1996-12-20 CZ CZ19981968A patent/CZ292503B6/cs not_active IP Right Cessation
- 1996-12-20 DK DK96944612T patent/DK0869947T3/da active
- 1996-12-20 IL IL12504896A patent/IL125048A/en not_active IP Right Cessation
- 1996-12-20 AT AT96944612T patent/ATE226575T1/de not_active IP Right Cessation
- 1996-12-20 PT PT96944612T patent/PT869947E/pt unknown
- 1996-12-20 EP EP96944612A patent/EP0869947B1/en not_active Expired - Lifetime
1997
- 1997-01-28 TW TW086101091A patent/TW518324B/zh not_active IP Right Cessation
1998
- 1998-06-22 MX MX9805063A patent/MX9805063A/es not_active IP Right Cessation
- 1998-06-22 NO NO19982901A patent/NO311572B1/no unknown
2000
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Also Published As

Publication number	Publication date
AU722513B2 (en)	2000-08-03
PL190217B1 (pl)	2005-11-30
IL125048A0 (en)	1999-01-26
RU2177475C2 (ru)	2001-12-27
CN1209123A (zh)	1999-02-24
EP0869947B1 (en)	2002-10-23
NZ325802A (en)	2000-05-26
NO311572B1 (no)	2001-12-10
WO1997023465A1 (en)	1997-07-03
CZ196898A3 (cs)	1998-09-16
AU1303697A (en)	1997-07-17
CN1318406C (zh)	2007-05-30
EP0869947A1 (en)	1998-10-14
JP2000505069A (ja)	2000-04-25
HUP9901065A2 (hu)	1999-09-28
HUP9901065A3 (en)	2001-10-29
MX9805063A (es)	1998-10-31
CZ292503B6 (cs)	2003-10-15
JP4198752B2 (ja)	2008-12-17
KR19990076734A (ko)	1999-10-15
BR9612232A (pt)	1999-07-13
NO982901L (no)	1998-08-24
US6472396B1 (en)	2002-10-29
DE19548624A1 (de)	1997-06-26
TW518324B (en)	2003-01-21
US6110924A (en)	2000-08-29
KR100440035B1 (ko)	2004-09-18
DK0869947T3 (da)	2003-02-24
NO982901D0 (no)	1998-06-22
ATE226575T1 (de)	2002-11-15
PL327466A1 (en)	1998-12-07
ES2184903T3 (es)	2003-04-16
ZA9610765B (en)	1998-07-17
DE69624500T2 (de)	2003-07-17
PT869947E (pt)	2003-03-31
DE69624500D1 (de)	2002-11-28

Publication	Publication Date	Title
IL125048A (en)	2004-02-19	History of barbituric acid and pharmaceutical preparations containing them to inhibit the metropolitan matrix
AU746853B2 (en)	2002-05-02	Barbituric acid derivatives with antimetastatic and antitumor activity
KR101258504B1 (ko)	2013-04-26	히스톤 데아세틸라제의 억제제
EP1701944B1 (en)	2009-07-29	2-(amino-substituted)-4-aryl pyramidines and related compounds useful for treating inflammatory diseases
AU768309B2 (en)	2003-12-04	New pyrimidine-2,4,6-trione derivatives, processes for their production and pharmaceutical agents containing these compounds
CA2240845C (en)	2006-09-19	New barbituric acid derivatives, processes for their production and pharmaceutical agents containing these compounds
AU722513C (en)	2001-02-22	New barbituric acid derivatives, processes for their production and pharmaceutical agents containing these compounds
AU2002302470C1 (en)	2008-07-24	Pyrimidine-2,4,6-trione derivatives, processes for their production and pharmaceutical agents containing them
JP2008133269A (ja)	2008-06-12	１，４−ベンゾチアジン−３−オン骨格又は３，４−ジヒドロキノリン−２−オン骨格を有する新規化合物
AU2002302470A1 (en)	2003-04-03	Pyrimidine-2,4,6-trione derivatives, processes for their production and pharmaceutical agents containing them

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Date	Code	Title	Description
2004-07-25	FF	Patent granted
2007-08-19	MM9K	Patent not in force due to non-payment of renewal fees