SK13002000A3 - Deriváty meta-azacyklickej aminobenzoovej kyseliny a ich deriváty, ktoré sú antagonisty integrínu - Google Patents

Deriváty meta-azacyklickej aminobenzoovej kyseliny a ich deriváty, ktoré sú antagonisty integrínu Download PDF

Info

Publication number: SK13002000A3
Authority: SK; Slovakia
Prior art keywords: added; solution; mol; reaction mixture; product
Prior art date: 1998-03-04

Application number

SK1300-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Thomas E. Rogers

Peter G. Ruminski

Original Assignee

G. D. Searle & Co.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-03-04

Filing date

1999-02-22

Publication date

2001-07-10

1999-02-22 Application filed by G. D. Searle & Co. filed Critical G. D. Searle & Co.

2001-07-10 Publication of SK13002000A3 publication Critical patent/SK13002000A3/sk

Links

239000005557 antagonist Substances 0.000 title abstract description 15
108010044426 integrins Proteins 0.000 title description 24
102000006495 integrins Human genes 0.000 title description 24
150000005415 aminobenzoic acids Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 89
150000003839 salts Chemical class 0.000 claims abstract description 15
238000000034 method Methods 0.000 claims description 55
238000011282 treatment Methods 0.000 claims description 26
206010028980 Neoplasm Diseases 0.000 claims description 22
239000003814 drug Substances 0.000 claims description 16
230000033115 angiogenesis Effects 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
208000001132 Osteoporosis Diseases 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
208000002780 macular degeneration Diseases 0.000 claims description 6
230000015590 smooth muscle cell migration Effects 0.000 claims description 6
230000004614 tumor growth Effects 0.000 claims description 6
206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
208000037147 Hypercalcaemia Diseases 0.000 claims description 3
201000011510 cancer Diseases 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
230000000148 hypercalcaemia Effects 0.000 claims description 3
230000036210 malignancy Effects 0.000 claims description 3
230000001404 mediated effect Effects 0.000 claims description 3
241000124008 Mammalia Species 0.000 claims description 2
208000030915 hypercalcemia disease Diseases 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 9
CTCHDPAJHVDPRN-UHFFFAOYSA-N integrin Chemical compound C=1C(OC)=CC(O)=C(C(C=2CC=C(C)C)=O)C=1OC=2C1=CC=C(O)C=C1O CTCHDPAJHVDPRN-UHFFFAOYSA-N 0.000 claims 1
102000008607 Integrin beta3 Human genes 0.000 abstract description 4
108010020950 Integrin beta3 Proteins 0.000 abstract description 4
239000000243 solution Substances 0.000 description 154
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 117
239000000047 product Substances 0.000 description 115
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 104
239000011541 reaction mixture Substances 0.000 description 95
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 89
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
238000002360 preparation method Methods 0.000 description 80
238000005481 NMR spectroscopy Methods 0.000 description 79
239000000203 mixture Substances 0.000 description 75
239000007787 solid Substances 0.000 description 74
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 74
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 53
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
239000000460 chlorine Substances 0.000 description 36
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 34
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 32
235000019441 ethanol Nutrition 0.000 description 32
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
235000002639 sodium chloride Nutrition 0.000 description 30
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 29
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 29
229910000041 hydrogen chloride Inorganic materials 0.000 description 29
238000003756 stirring Methods 0.000 description 28
235000019439 ethyl acetate Nutrition 0.000 description 27
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
229960004132 diethyl ether Drugs 0.000 description 25
238000001914 filtration Methods 0.000 description 25
229910052943 magnesium sulfate Inorganic materials 0.000 description 24
235000019341 magnesium sulphate Nutrition 0.000 description 24
239000002904 solvent Substances 0.000 description 24
239000000126 substance Substances 0.000 description 24
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 20
239000002244 precipitate Substances 0.000 description 20
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 19
239000012044 organic layer Substances 0.000 description 19
238000010992 reflux Methods 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
150000002148 esters Chemical class 0.000 description 18
-1 methoxyethoxymethyl Chemical group 0.000 description 18
230000002829 reductive effect Effects 0.000 description 18
239000010410 layer Substances 0.000 description 17
239000011780 sodium chloride Substances 0.000 description 17
239000000725 suspension Substances 0.000 description 17
230000005764 inhibitory process Effects 0.000 description 16
238000012360 testing method Methods 0.000 description 16
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
238000004007 reversed phase HPLC Methods 0.000 description 15
238000004108 freeze drying Methods 0.000 description 14
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 13
239000002253 acid Substances 0.000 description 12
238000004458 analytical method Methods 0.000 description 12
230000002401 inhibitory effect Effects 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 11
238000003556 assay Methods 0.000 description 11
239000003153 chemical reaction reagent Substances 0.000 description 11
239000000706 filtrate Substances 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
108010031318 Vitronectin Proteins 0.000 description 10
102100035140 Vitronectin Human genes 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
150000002466 imines Chemical class 0.000 description 10
238000004452 microanalysis Methods 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
102000005962 receptors Human genes 0.000 description 10
108020003175 receptors Proteins 0.000 description 10
DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 9
241000282414 Homo sapiens Species 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000012267 brine Substances 0.000 description 9
239000008367 deionised water Substances 0.000 description 9
229910021641 deionized water Inorganic materials 0.000 description 9
239000000843 powder Substances 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
QPEJHSFTZVMSJH-UHFFFAOYSA-N 3-amino-5-hydroxybenzoic acid Chemical compound NC1=CC(O)=CC(C(O)=O)=C1 QPEJHSFTZVMSJH-UHFFFAOYSA-N 0.000 description 8
206010027476 Metastases Diseases 0.000 description 8
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 8
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 8
238000001816 cooling Methods 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
230000009401 metastasis Effects 0.000 description 8
239000012299 nitrogen atmosphere Substances 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-UHFFFAOYSA-N 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
229940079593 drug Drugs 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000003446 ligand Substances 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
238000000746 purification Methods 0.000 description 7
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 6
XXFFEGBFFXHMTF-UHFFFAOYSA-N 5-bromo-3-chloro-2-hydroxybenzaldehyde Chemical compound OC1=C(Cl)C=C(Br)C=C1C=O XXFFEGBFFXHMTF-UHFFFAOYSA-N 0.000 description 6
QNSRWUDUYCZRQJ-UHFFFAOYSA-N 5-chloro-2-hydroxy-3-iodobenzaldehyde Chemical compound OC1=C(I)C=C(Cl)C=C1C=O QNSRWUDUYCZRQJ-UHFFFAOYSA-N 0.000 description 6
IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 6
208000006386 Bone Resorption Diseases 0.000 description 6
235000019502 Orange oil Nutrition 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 6
230000008485 antagonism Effects 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
230000024279 bone resorption Effects 0.000 description 6
239000007789 gas Substances 0.000 description 6
239000010502 orange oil Substances 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
FABVMBDCVAJXMB-UHFFFAOYSA-N 3,5-dichloro-2-hydroxybenzaldehyde Chemical compound OC1=C(Cl)C=C(Cl)C=C1C=O FABVMBDCVAJXMB-UHFFFAOYSA-N 0.000 description 5
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
VYKYVFPHGKLLDF-UHFFFAOYSA-N 5-bromo-2-hydroxy-3-iodobenzaldehyde Chemical compound OC1=C(I)C=C(Br)C=C1C=O VYKYVFPHGKLLDF-UHFFFAOYSA-N 0.000 description 5
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 5
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
235000001671 coumarin Nutrition 0.000 description 5
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 5
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 5
229940046892 lead acetate Drugs 0.000 description 5
230000009826 neoplastic cell growth Effects 0.000 description 5
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 5
210000002381 plasma Anatomy 0.000 description 5
230000008569 process Effects 0.000 description 5
208000037803 restenosis Diseases 0.000 description 5
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 5
UYEMGAFJOZZIFP-UHFFFAOYSA-N 3,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC(O)=C1 UYEMGAFJOZZIFP-UHFFFAOYSA-N 0.000 description 4
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical class OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
206010012689 Diabetic retinopathy Diseases 0.000 description 4
101000803709 Homo sapiens Vitronectin Proteins 0.000 description 4
208000010191 Osteitis Deformans Diseases 0.000 description 4
208000027868 Paget disease Diseases 0.000 description 4
239000002671 adjuvant Substances 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
238000004090 dissolution Methods 0.000 description 4
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
208000027202 mammary Paget disease Diseases 0.000 description 4
239000000463 material Substances 0.000 description 4
210000002997 osteoclast Anatomy 0.000 description 4
239000002245 particle Substances 0.000 description 4
230000001575 pathological effect Effects 0.000 description 4
DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
239000000758 substrate Substances 0.000 description 4
230000005747 tumor angiogenesis Effects 0.000 description 4
IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 3
UYBWIEGTWASWSR-UHFFFAOYSA-N 1,3-diaminopropan-2-ol Chemical compound NCC(O)CN UYBWIEGTWASWSR-UHFFFAOYSA-N 0.000 description 3
JHZOXYGFQMROFJ-UHFFFAOYSA-N 3,5-dibromo-2-hydroxybenzaldehyde Chemical compound OC1=C(Br)C=C(Br)C=C1C=O JHZOXYGFQMROFJ-UHFFFAOYSA-N 0.000 description 3
KNOYZLVIXXBBIB-UHFFFAOYSA-N 3-bromo-5-chloro-2-hydroxybenzaldehyde Chemical compound OC1=C(Br)C=C(Cl)C=C1C=O KNOYZLVIXXBBIB-UHFFFAOYSA-N 0.000 description 3
MKKSTJKBKNCMRV-UHFFFAOYSA-N 5-bromo-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Br)C=C1C=O MKKSTJKBKNCMRV-UHFFFAOYSA-N 0.000 description 3
FUGKCSRLAQKUHG-UHFFFAOYSA-N 5-chloro-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Cl)C=C1C=O FUGKCSRLAQKUHG-UHFFFAOYSA-N 0.000 description 3
GBUALRXLRRQXGH-UHFFFAOYSA-N 5-hydroxy-1,3-diazinane-2-thione Chemical compound OC1CNC(=S)NC1 GBUALRXLRRQXGH-UHFFFAOYSA-N 0.000 description 3
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical class O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 3
238000006418 Brown reaction Methods 0.000 description 3
GRJLICHBYGPIKS-UHFFFAOYSA-N C(C1=CC=CC=C1)(=O)O.N1CNCC=C1 Chemical compound C(C1=CC=CC=C1)(=O)O.N1CNCC=C1 GRJLICHBYGPIKS-UHFFFAOYSA-N 0.000 description 3
102000000844 Cell Surface Receptors Human genes 0.000 description 3
108010001857 Cell Surface Receptors Proteins 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
108010012088 Fibrinogen Receptors Proteins 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
102100022337 Integrin alpha-V Human genes 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
201000004681 Psoriasis Diseases 0.000 description 3
208000017442 Retinal disease Diseases 0.000 description 3
206010038923 Retinopathy Diseases 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
230000002776 aggregation Effects 0.000 description 3
238000004220 aggregation Methods 0.000 description 3
229940072056 alginate Drugs 0.000 description 3
229920000615 alginic acid Chemical class 0.000 description 3
235000010443 alginic acid Nutrition 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
150000001413 amino acids Chemical group 0.000 description 3
239000012300 argon atmosphere Substances 0.000 description 3
206010003246 arthritis Diseases 0.000 description 3
239000002585 base Substances 0.000 description 3
230000009286 beneficial effect Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
230000021164 cell adhesion Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229960000956 coumarin Drugs 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
238000004896 high resolution mass spectrometry Methods 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
208000028169 periodontal disease Diseases 0.000 description 3
239000012071 phase Substances 0.000 description 3
210000004623 platelet-rich plasma Anatomy 0.000 description 3
238000002953 preparative HPLC Methods 0.000 description 3
230000002265 prevention Effects 0.000 description 3
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
238000012546 transfer Methods 0.000 description 3
210000004881 tumor cell Anatomy 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
229910052725 zinc Inorganic materials 0.000 description 3
239000011701 zinc Substances 0.000 description 3
YMXHPSHLTSZXKH-RVBZMBCESA-N (2,5-dioxopyrrolidin-1-yl) 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)ON1C(=O)CCC1=O YMXHPSHLTSZXKH-RVBZMBCESA-N 0.000 description 2
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical group O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
WSJBVTXFHPLKJB-UHFFFAOYSA-N 3,5-diiodo-2-(2-methoxyethoxymethoxy)benzaldehyde Chemical compound COCCOCOC1=C(I)C=C(I)C=C1C=O WSJBVTXFHPLKJB-UHFFFAOYSA-N 0.000 description 2
MEPAVMTWMMMPIZ-UHFFFAOYSA-N 3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]benzoic acid Chemical compound C1C(O)CNC(NC=2C=C(C=C(O)C=2)C(O)=O)=N1 MEPAVMTWMMMPIZ-UHFFFAOYSA-N 0.000 description 2
UYWFPYSTOCFFQX-UHFFFAOYSA-N 5-chloro-3-iodo-2-(2-methoxyethoxymethoxy)benzaldehyde Chemical compound COCCOCOC1=C(I)C=C(Cl)C=C1C=O UYWFPYSTOCFFQX-UHFFFAOYSA-N 0.000 description 2
QAUBTCSLKHMNQG-UHFFFAOYSA-N 6,8-dibromochromen-2-one Chemical compound O1C(=O)C=CC2=CC(Br)=CC(Br)=C21 QAUBTCSLKHMNQG-UHFFFAOYSA-N 0.000 description 2
VXNXVBSMMLEIIB-UHFFFAOYSA-N 6,8-dichlorochromen-2-one Chemical compound O1C(=O)C=CC2=CC(Cl)=CC(Cl)=C21 VXNXVBSMMLEIIB-UHFFFAOYSA-N 0.000 description 2
BFNNJTYAPVFZKH-UHFFFAOYSA-N 6-bromo-8-chlorochromen-2-one Chemical compound C1=CC(=O)OC2=C1C=C(Br)C=C2Cl BFNNJTYAPVFZKH-UHFFFAOYSA-N 0.000 description 2
QIYDOYNZBNLOCB-UHFFFAOYSA-N 6-chloro-8-iodochromen-2-one Chemical compound O1C(=O)C=CC2=CC(Cl)=CC(I)=C21 QIYDOYNZBNLOCB-UHFFFAOYSA-N 0.000 description 2
241000283707 Capra Species 0.000 description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
102000008946 Fibrinogen Human genes 0.000 description 2
108010049003 Fibrinogen Proteins 0.000 description 2
108010001336 Horseradish Peroxidase Proteins 0.000 description 2
208000034827 Neointima Diseases 0.000 description 2
206010029113 Neovascularisation Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000005417 aminobenzoic acid derivatives Chemical class 0.000 description 2
230000003042 antagnostic effect Effects 0.000 description 2
230000001745 anti-biotin effect Effects 0.000 description 2
230000000840 anti-viral effect Effects 0.000 description 2
239000003443 antiviral agent Substances 0.000 description 2
230000006907 apoptotic process Effects 0.000 description 2
238000013459 approach Methods 0.000 description 2
108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Natural products N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
239000011575 calcium Substances 0.000 description 2
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000007979 citrate buffer Substances 0.000 description 2
150000004775 coumarins Chemical class 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
230000001747 exhibiting effect Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
229940012952 fibrinogen Drugs 0.000 description 2
238000009472 formulation Methods 0.000 description 2
210000002196 fr. b Anatomy 0.000 description 2
210000003918 fraction a Anatomy 0.000 description 2
239000012458 free base Substances 0.000 description 2
230000006870 function Effects 0.000 description 2
125000001188 haloalkyl group Chemical group 0.000 description 2
229940106780 human fibrinogen Drugs 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
206010020718 hyperplasia Diseases 0.000 description 2
238000002329 infrared spectrum Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000009545 invasion Effects 0.000 description 2
238000005342 ion exchange Methods 0.000 description 2
150000002596 lactones Chemical class 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000003760 magnetic stirring Methods 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
201000001441 melanoma Diseases 0.000 description 2
238000002156 mixing Methods 0.000 description 2
230000011164 ossification Effects 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
GXLJZLBKWSJXFP-UHFFFAOYSA-N phenyl propanoate;hydrochloride Chemical compound Cl.CCC(=O)OC1=CC=CC=C1 GXLJZLBKWSJXFP-UHFFFAOYSA-N 0.000 description 2
239000004033 plastic Substances 0.000 description 2
229920003023 plastic Polymers 0.000 description 2
229920000573 polyethylene Polymers 0.000 description 2
239000013641 positive control Substances 0.000 description 2
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
230000002441 reversible effect Effects 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
239000012453 solvate Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
229920002554 vinyl polymer Chemical class 0.000 description 2
230000003612 virological effect Effects 0.000 description 2
VRXONKVNZOTTIV-UHFFFAOYSA-N (2-hydroxy-3,5-diiodophenyl) propanoate Chemical compound C(CC)(=O)OC1=C(C(=CC(=C1)I)I)O VRXONKVNZOTTIV-UHFFFAOYSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
NNWAARLSYSBVPB-UHFFFAOYSA-N 1h-imidazole-4,5-dicarboxamide Chemical compound NC(=O)C=1N=CNC=1C(N)=O NNWAARLSYSBVPB-UHFFFAOYSA-N 0.000 description 1
IIUBNFWCBHOHQJ-UHFFFAOYSA-N 2-aminoacetic acid;1-hydroxypyrrolidine-2,5-dione Chemical compound NCC(O)=O.ON1C(=O)CCC1=O IIUBNFWCBHOHQJ-UHFFFAOYSA-N 0.000 description 1
MWGATWIBSKHFMR-UHFFFAOYSA-N 2-anilinoethanol Chemical compound OCCNC1=CC=CC=C1 MWGATWIBSKHFMR-UHFFFAOYSA-N 0.000 description 1
MYWSBJKVOUZCIA-UHFFFAOYSA-N 2-hydroxy-3,5-diiodobenzaldehyde Chemical compound OC1=C(I)C=C(I)C=C1C=O MYWSBJKVOUZCIA-UHFFFAOYSA-N 0.000 description 1
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
HRADVHZVMOMEPU-UHFFFAOYSA-N 3-iodopyrrolidine-2,5-dione Chemical compound IC1CC(=O)NC1=O HRADVHZVMOMEPU-UHFFFAOYSA-N 0.000 description 1
PPJDYEYTFNNFML-UHFFFAOYSA-N 4-amino-6-chloro-8-iodo-3,4-dihydrochromen-2-one;hydrochloride Chemical compound Cl.C1=C(Cl)C=C2C(N)CC(=O)OC2=C1I PPJDYEYTFNNFML-UHFFFAOYSA-N 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
208000010392 Bone Fractures Diseases 0.000 description 1
206010065687 Bone loss Diseases 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
108010010803 Gelatin Chemical class 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
SCCPDJAQCXWPTF-VKHMYHEASA-N Gly-Asp Chemical compound NCC(=O)N[C@H](C(O)=O)CC(O)=O SCCPDJAQCXWPTF-VKHMYHEASA-N 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
108700020129 Human immunodeficiency virus 1 p31 integrase Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020584 Hypercalcaemia of malignancy Diseases 0.000 description 1
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 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
102000012750 Membrane Glycoproteins Human genes 0.000 description 1
108010090054 Membrane Glycoproteins Proteins 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
RDYMUEJQFCLGFY-UHFFFAOYSA-N OC=1C=NC=NC1.CSC Chemical compound OC=1C=NC=NC1.CSC RDYMUEJQFCLGFY-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
238000003684 Perkin reaction Methods 0.000 description 1
108010035030 Platelet Membrane Glycoprotein IIb Proteins 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
241000287219 Serinus canaria Species 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
108010048673 Vitronectin Receptors Proteins 0.000 description 1
229910003106 Zn-Br Inorganic materials 0.000 description 1
QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
102000019997 adhesion receptor Human genes 0.000 description 1
108010013985 adhesion receptor Proteins 0.000 description 1
238000001042 affinity chromatography Methods 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
230000002491 angiogenic effect Effects 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
230000000843 anti-fungal effect Effects 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
230000008827 biological function Effects 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
230000008512 biological response Effects 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
238000000160 carbon, hydrogen and nitrogen elemental analysis Methods 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000004709 cell invasion Effects 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
230000035602 clotting Effects 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
210000000805 cytoplasm Anatomy 0.000 description 1
238000010908 decantation Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
125000006003 dichloroethyl group Chemical group 0.000 description 1
238000007865 diluting Methods 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
229940088679 drug related substance Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000008393 encapsulating agent Substances 0.000 description 1
230000012202 endocytosis Effects 0.000 description 1
210000003038 endothelium Anatomy 0.000 description 1
MUAQLURLPRJFAT-VIFPVBQESA-N ethyl (3s)-3-amino-3-(2-hydroxy-3,5-diiodophenyl)propanoate Chemical compound CCOC(=O)C[C@H](N)C1=CC(I)=CC(I)=C1O MUAQLURLPRJFAT-VIFPVBQESA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
210000002744 extracellular matrix Anatomy 0.000 description 1
238000010265 fast atom bombardment Methods 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 description 1
239000006260 foam Substances 0.000 description 1
210000001061 forehead Anatomy 0.000 description 1
239000004023 fresh frozen plasma Substances 0.000 description 1
239000008273 gelatin Chemical class 0.000 description 1
229920000159 gelatin Chemical class 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000012010 growth Effects 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
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 description 1
208000008750 humoral hypercalcemia of malignancy Diseases 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
229940124524 integrase inhibitor Drugs 0.000 description 1
239000002850 integrase inhibitor Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229910052740 iodine Inorganic materials 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
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000000395 magnesium oxide Substances 0.000 description 1
CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000003550 marker Substances 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 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
230000003287 optical effect Effects 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
210000002826 placenta Anatomy 0.000 description 1
230000010118 platelet activation Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
229940116357 potassium thiocyanate Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
YYFIGOPUHPDIBO-UHFFFAOYSA-N propanoic acid;hydrochloride Chemical compound Cl.CCC(O)=O YYFIGOPUHPDIBO-UHFFFAOYSA-N 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
238000010926 purge Methods 0.000 description 1
LTXJLQINBYSQFU-UHFFFAOYSA-N pyrimidin-5-ol Chemical compound OC1=CN=CN=C1 LTXJLQINBYSQFU-UHFFFAOYSA-N 0.000 description 1
210000003370 receptor cell Anatomy 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000007634 remodeling Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000013049 sediment Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000002002 slurry Substances 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
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
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000012289 standard assay Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000003068 static effect Effects 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229940086735 succinate Drugs 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
150000003585 thioureas Chemical class 0.000 description 1
210000001519 tissue Anatomy 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
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
- 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
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/12—Nitrogen atoms not forming part of a nitro radical
- C07D239/14—Nitrogen atoms not forming part of a nitro radical with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to said nitrogen atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Rheumatology (AREA)
Bioinformatics & Cheminformatics (AREA)
Physical Education & Sports Medicine (AREA)
Engineering & Computer Science (AREA)
Orthopedic Medicine & Surgery (AREA)
Epidemiology (AREA)
Obesity (AREA)
Immunology (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Pain & Pain Management (AREA)
Molecular Biology (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Oncology (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Indole Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK1300-2000A 1998-03-04 1999-02-22 Deriváty meta-azacyklickej aminobenzoovej kyseliny a ich deriváty, ktoré sú antagonisty integrínu SK13002000A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US3427098A	1998-03-04	1998-03-04
PCT/US1999/003281 WO1999044994A1 (en)	1998-03-04	1999-02-22	Meta-azacyclic amino benzoic acid compounds and derivatives thereof being integrin antagonists

Publications (1)

Publication Number	Publication Date
SK13002000A3 true SK13002000A3 (sk)	2001-07-10

Family

ID=21875345

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1300-2000A SK13002000A3 (sk)	1998-03-04	1999-02-22	Deriváty meta-azacyklickej aminobenzoovej kyseliny a ich deriváty, ktoré sú antagonisty integrínu

Country Status (29)

Country	Link
EP (1)	EP1060164A1 (is)
JP (1)	JP2002505323A (is)
KR (1)	KR20010041584A (is)
CN (1)	CN1214011C (is)
AP (1)	AP1244A (is)
AR (1)	AR018139A1 (is)
AU (1)	AU753230B2 (is)
BG (1)	BG104740A (is)
BR (1)	BR9908470A (is)
CA (1)	CA2322207A1 (is)
EA (1)	EA200000804A1 (is)
EE (1)	EE200000506A (is)
GE (1)	GEP20033118B (is)
HR (1)	HRP20000574A2 (is)
HU (1)	HUP0100865A3 (is)
ID (1)	ID25591A (is)
IL (1)	IL137653A0 (is)
IS (1)	IS5582A (is)
MY (1)	MY123908A (is)
NO (1)	NO315703B1 (is)
NZ (1)	NZ506598A (is)
OA (1)	OA11530A (is)
PL (1)	PL342726A1 (is)
SK (1)	SK13002000A3 (is)
TR (1)	TR200002542T2 (is)
UA (1)	UA71906C2 (is)
WO (1)	WO1999044994A1 (is)
YU (1)	YU52000A (is)
ZA (1)	ZA994406B (is)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9805655D0 (en)	1998-03-16	1998-05-13	Celltech Therapeutics Ltd	Chemical compounds
GB9814414D0 (en)	1998-07-03	1998-09-02	Celltech Therapeutics Ltd	Chemical compounds
GB9821061D0 (en)	1998-09-28	1998-11-18	Celltech Therapeutics Ltd	Chemical compounds
GB9826174D0 (en)	1998-11-30	1999-01-20	Celltech Therapeutics Ltd	Chemical compounds
US6518283B1 (en)	1999-05-28	2003-02-11	Celltech R&D Limited	Squaric acid derivatives
US6455539B2 (en)	1999-12-23	2002-09-24	Celltech R&D Limited	Squaric acid derivates
AU2001248553A1 (en)	2000-04-17	2001-10-30	Celltech R And D Limited	Enamine derivatives as cell adhesion molecules
US6545013B2 (en)	2000-05-30	2003-04-08	Celltech R&D Limited	2,7-naphthyridine derivatives
US6403608B1 (en)	2000-05-30	2002-06-11	Celltech R&D, Ltd.	3-Substituted isoquinolin-1-yl derivatives
US6921767B2 (en) *	2000-06-15	2005-07-26	Pharmacia Corporation	Cycloalkyl alkanoic acids as integrin receptor antagonists derivatives
EP1305291A1 (en)	2000-08-02	2003-05-02	Celltech R&D Limited	3-substituted isoquinolin-1-yl derivatives
MXPA05006732A (es) *	2002-12-20	2005-09-08	Pharmacia Corp	El isomero r de compuesto de beta-aminoacido como derivados de antagonistas de receptor de la integrina.
UA87854C2 (en)	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
CA2612979A1 (en) *	2005-06-10	2006-12-21	Bipar Sciences, Inc.	Parp modulators and treatment of cancer
WO2008108944A2 (en)	2007-03-01	2008-09-12	Mallinckrodt Inc.	Integrated photoactive small molecules and uses thereof
JP4792124B1 (ja) *	2010-11-15	2011-10-12	エフイートレード株式会社	車両用保護フィルムの型取り方法、及び、車両用保護フィルムの製造方法
WO2014015054A1 (en)	2012-07-18	2014-01-23	Saint Louis University	Beta amino acid derivatives as integrin antagonists
US8716226B2 (en)	2012-07-18	2014-05-06	Saint Louis University	3,5 phenyl-substituted beta amino acid derivatives as integrin antagonists
SG11201609050UA (en)	2014-05-30	2016-12-29	Pfizer	Carbonitrile derivatives as selective androgen receptor modulators
CN106659162B (zh) *	2014-06-04	2020-10-27	孟山都技术公司	3,6-二氯水杨酸化合物以及相关合成方法
BR112018012981A2 (pt)	2015-12-30	2018-12-04	Saint Louis University	derivados do ácido meta-azacíclico amino benzoico como antagonistas de pan integrina com melhores propriedades farmacocinéticas
EP4151632A4 (en)	2020-05-14	2024-04-24	UBE Corporation	1, 4, 5, 6-tetrahydropyrimidine-2-amine derivative
WO2023275715A1 (en)	2021-06-30	2023-01-05	Pfizer Inc.	Metabolites of selective androgen receptor modulators
US20250049806A1 (en)	2021-11-12	2025-02-13	Ube Corporation	Pharmaceutical composition for providing treatment for or preventing alport syndrome

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BR9610422A (pt) *	1995-08-30	1999-07-13	Searle & Co	Derivados de meta-guanidina uréia tiouréia ou ácido aminobenzóico azacíclico como antagonistas de integrina

1999
- 1999-02-11 ZA ZA9904406A patent/ZA994406B/xx unknown
- 1999-02-22 UA UA2000095148A patent/UA71906C2/uk unknown
- 1999-02-22 WO PCT/US1999/003281 patent/WO1999044994A1/en not_active Ceased
- 1999-02-22 BR BR9908470-8A patent/BR9908470A/pt not_active Application Discontinuation
- 1999-02-22 GE GEAP19995537A patent/GEP20033118B/en unknown
- 1999-02-22 TR TR2000/02542T patent/TR200002542T2/xx unknown
- 1999-02-22 KR KR1020007009774A patent/KR20010041584A/ko not_active Ceased
- 1999-02-22 EP EP99937927A patent/EP1060164A1/en active Pending
- 1999-02-22 PL PL99342726A patent/PL342726A1/xx unknown
- 1999-02-22 YU YU52000A patent/YU52000A/sh unknown
- 1999-02-22 AP APAP/P/2000/001893A patent/AP1244A/en active
- 1999-02-22 EA EA200000804A patent/EA200000804A1/ru unknown
- 1999-02-22 CN CNB998035815A patent/CN1214011C/zh not_active Expired - Fee Related
- 1999-02-22 OA OA1200000238A patent/OA11530A/en unknown
- 1999-02-22 EE EEP200000506A patent/EE200000506A/xx unknown
- 1999-02-22 SK SK1300-2000A patent/SK13002000A3/sk unknown
- 1999-02-22 NZ NZ506598A patent/NZ506598A/en unknown
- 1999-02-22 HU HU0100865A patent/HUP0100865A3/hu unknown
- 1999-02-22 HR HR20000574A patent/HRP20000574A2/hr not_active Application Discontinuation
- 1999-02-22 AU AU32947/99A patent/AU753230B2/en not_active Ceased
- 1999-02-22 JP JP2000534538A patent/JP2002505323A/ja active Pending
- 1999-02-22 ID IDW20001695A patent/ID25591A/id unknown
- 1999-02-22 CA CA002322207A patent/CA2322207A1/en not_active Abandoned
- 1999-02-22 IL IL13765399A patent/IL137653A0/xx unknown
- 1999-03-02 AR ARP990100880A patent/AR018139A1/es unknown
- 1999-03-03 MY MYPI99000772A patent/MY123908A/en unknown
2000
- 2000-08-04 IS IS5582A patent/IS5582A/is unknown
- 2000-08-30 NO NO20004316A patent/NO315703B1/no not_active IP Right Cessation
- 2000-09-01 BG BG104740A patent/BG104740A/xx unknown

Also Published As

Publication number	Publication date
IL137653A0 (en)	2001-10-31
CN1291978A (zh)	2001-04-18
UA71906C2 (en)	2005-01-17
JP2002505323A (ja)	2002-02-19
GEP20033118B (en)	2003-11-25
NO20004316D0 (no)	2000-08-30
AP1244A (en)	2004-02-04
NO315703B1 (no)	2003-10-13
IS5582A (is)	2000-08-04
BR9908470A (pt)	2000-12-05
AP2000001893A0 (en)	2000-09-30
CA2322207A1 (en)	1999-09-10
HUP0100865A3 (en)	2001-11-28
BG104740A (en)	2001-02-28
WO1999044994A1 (en)	1999-09-10
MY123908A (en)	2006-06-30
OA11530A (en)	2004-05-17
NZ506598A (en)	2003-07-25
YU52000A (sh)	2003-02-28
EA200000804A1 (ru)	2001-04-23
EE200000506A (et)	2002-04-15
AR018139A1 (es)	2001-10-31
AU3294799A (en)	1999-09-20
HUP0100865A2 (hu)	2001-08-28
AU753230B2 (en)	2002-10-10
EP1060164A1 (en)	2000-12-20
ZA994406B (en)	2000-02-11
ID25591A (id)	2000-10-19
HRP20000574A2 (en)	2001-08-31
PL342726A1 (en)	2001-07-02
KR20010041584A (ko)	2001-05-25
NO20004316L (no)	2000-11-06
CN1214011C (zh)	2005-08-10
TR200002542T2 (tr)	2001-05-21

Publication	Publication Date	Title
SK13002000A3 (sk)	2001-07-10	Deriváty meta-azacyklickej aminobenzoovej kyseliny a ich deriváty, ktoré sú antagonisty integrínu
US6677308B1 (en)	2004-01-13	Meta-substituted phenylene sulphonamide derivatives
US6251944B1 (en)	2001-06-26	Para-substituted phenylene derivatives
AU702487B2 (en)	1999-02-25	Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid derivatives as integrin antagonists
WO1997036858A1 (en)	1997-10-09	Cyclopropyl alkanoic acid derivatives
WO1999052896A1 (en)	1999-10-21	Heterocyclic glycyl beta-alanine derivatives as vitronectin antagonists
US6372719B1 (en)	2002-04-16	ανβ3 integrin antagonists in combination with chemotherapeutic agents
US6013651A (en)	2000-01-11	Meta-azacyclic amino benzoic acid compounds and derivatives thereof
EP0804418B1 (en)	2003-03-26	Platelet aggregation inhibitors
CZ20011963A3 (cs)	2001-11-14	Antagonista vitronektinového receptoru
US6689754B1 (en)	2004-02-10	Heterocyclic glycyl β-alanine derivatives
JP2004513088A (ja)	2004-04-30	ラクトンインテグリン拮抗薬
CZ20003218A3 (cs)	2001-03-14	Deriváty meta-azacyklické aminobenzoové kyseliny a jejich deriváty, které jsou antagonisty integrinu
MXPA00008427A (en)	2002-07-25	Meta-azacyclic amino benzoic acid compounds and derivatives thereof being integrin antagonists
MXPA00009967A (en)	2001-07-31	Heterocyclic glycyl beta-alanine derivatives as vitronectin antagonists
EP1157985A1 (en)	2001-11-28	Para- substituted phenylene derivatives and their use as integrin antagonists