NO315703B1 - Meta azasykliske aminobenzosyreforbindelser og derivater derav som er integrinatantagonister - Google Patents

Meta azasykliske aminobenzosyreforbindelser og derivater derav som er integrinatantagonister Download PDF

Info

Publication number: NO315703B1
Authority: NO; Norway
Prior art keywords: added; mol; solution; product; give
Prior art date: 1998-03-04

Application number

NO20004316A

Other languages

English (en)

Norwegian (no)

Other versions

NO20004316L (no

NO20004316D0 (no

Inventor

Thomas E Rogers

Peter G Ruminski

Original Assignee

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

2000-08-30

Publication date

2003-10-13

2000-08-30 Application filed by Searle & Co filed Critical Searle & Co

2000-08-30 Publication of NO20004316D0 publication Critical patent/NO20004316D0/no

2000-11-06 Publication of NO20004316L publication Critical patent/NO20004316L/no

2003-10-13 Publication of NO315703B1 publication Critical patent/NO315703B1/no

Links

108010044426 integrins Proteins 0.000 title claims description 27
102000006495 integrins Human genes 0.000 title claims description 27
239000005557 antagonist Substances 0.000 title description 14
150000005415 aminobenzoic acids Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 91
206010028980 Neoplasm Diseases 0.000 claims description 18
239000003814 drug Substances 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
229940079593 drug Drugs 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
206010027476 Metastases Diseases 0.000 claims description 8
230000033115 angiogenesis Effects 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
208000001132 Osteoporosis Diseases 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 6
208000002780 macular degeneration Diseases 0.000 claims description 6
230000009401 metastasis Effects 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
229910052799 carbon Inorganic materials 0.000 claims description 5
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 3
230000001404 mediated effect Effects 0.000 claims description 3
208000008750 humoral hypercalcemia of malignancy Diseases 0.000 claims description 2
239000000047 product Substances 0.000 description 116
239000000243 solution Substances 0.000 description 99
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 94
239000011541 reaction mixture Substances 0.000 description 92
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 77
239000007787 solid Substances 0.000 description 73
238000005481 NMR spectroscopy Methods 0.000 description 71
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
239000000203 mixture Substances 0.000 description 59
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
238000004519 manufacturing process Methods 0.000 description 55
238000000034 method Methods 0.000 description 50
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 46
238000006243 chemical reaction Methods 0.000 description 43
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
239000000460 chlorine Substances 0.000 description 34
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
238000003756 stirring Methods 0.000 description 32
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 30
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
235000019439 ethyl acetate Nutrition 0.000 description 28
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
238000002360 preparation method Methods 0.000 description 26
238000001914 filtration Methods 0.000 description 25
239000003921 oil Substances 0.000 description 24
235000019198 oils Nutrition 0.000 description 24
235000019441 ethanol Nutrition 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
239000012267 brine Substances 0.000 description 21
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
229910052757 nitrogen Inorganic materials 0.000 description 20
239000002244 precipitate Substances 0.000 description 20
239000012074 organic phase 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
230000005764 inhibitory process Effects 0.000 description 18
230000002829 reductive effect Effects 0.000 description 18
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 17
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
235000002639 sodium chloride Nutrition 0.000 description 15
238000004108 freeze drying Methods 0.000 description 14
239000003656 tris buffered saline Substances 0.000 description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
238000003556 assay Methods 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
150000002148 esters Chemical class 0.000 description 12
-1 methoxyethoxymethyl Chemical group 0.000 description 12
239000003153 chemical reaction reagent Substances 0.000 description 11
239000000706 filtrate Substances 0.000 description 11
239000012071 phase Substances 0.000 description 11
102000005962 receptors Human genes 0.000 description 11
108020003175 receptors Proteins 0.000 description 11
239000003039 volatile agent Substances 0.000 description 11
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 10
229910052801 chlorine Inorganic materials 0.000 description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000004458 analytical method Methods 0.000 description 9
238000001816 cooling Methods 0.000 description 9
150000002466 imines Chemical class 0.000 description 9
239000000843 powder Substances 0.000 description 9
239000002002 slurry Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
238000012360 testing method Methods 0.000 description 9
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 9
ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 8
239000000463 material 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
239000000725 suspension Substances 0.000 description 8
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 7
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 7
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 7
108010031318 Vitronectin Proteins 0.000 description 7
102100035140 Vitronectin Human genes 0.000 description 7
239000002253 acid Substances 0.000 description 7
150000003840 hydrochlorides Chemical class 0.000 description 7
239000003446 ligand Substances 0.000 description 7
DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 7
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 7
238000000746 purification Methods 0.000 description 7
BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-UHFFFAOYSA-N 0.000 description 6
QPEJHSFTZVMSJH-UHFFFAOYSA-N 3-amino-5-hydroxybenzoic acid Chemical compound NC1=CC(O)=CC(C(O)=O)=C1 QPEJHSFTZVMSJH-UHFFFAOYSA-N 0.000 description 6
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical class OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-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
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
208000006386 Bone Resorption Diseases 0.000 description 6
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
101000803709 Homo sapiens Vitronectin Proteins 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
235000019502 Orange oil Nutrition 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
239000008346 aqueous phase Substances 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
201000010099 disease Diseases 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
230000000694 effects 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
238000002953 preparative HPLC Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-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
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 5
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 5
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
230000008485 antagonism Effects 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
201000011510 cancer Diseases 0.000 description 5
235000001671 coumarin Nutrition 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
230000009826 neoplastic cell growth Effects 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
230000002441 reversible effect Effects 0.000 description 5
239000012047 saturated solution Substances 0.000 description 5
239000011734 sodium Substances 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
229960000549 4-dimethylaminophenol Drugs 0.000 description 4
MKKSTJKBKNCMRV-UHFFFAOYSA-N 5-bromo-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Br)C=C1C=O MKKSTJKBKNCMRV-UHFFFAOYSA-N 0.000 description 4
FUGKCSRLAQKUHG-UHFFFAOYSA-N 5-chloro-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Cl)C=C1C=O FUGKCSRLAQKUHG-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
102000000844 Cell Surface Receptors Human genes 0.000 description 4
108010001857 Cell Surface Receptors Proteins 0.000 description 4
206010012689 Diabetic retinopathy Diseases 0.000 description 4
102100023038 WD and tetratricopeptide repeats protein 1 Human genes 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
230000001745 anti-biotin effect Effects 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
230000009286 beneficial effect Effects 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
230000001575 pathological effect Effects 0.000 description 4
239000008177 pharmaceutical agent Substances 0.000 description 4
210000002381 plasma Anatomy 0.000 description 4
210000004623 platelet-rich plasma Anatomy 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
230000002265 prevention Effects 0.000 description 4
108090000765 processed proteins & peptides Proteins 0.000 description 4
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
208000037803 restenosis Diseases 0.000 description 4
238000004007 reversed phase HPLC Methods 0.000 description 4
208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
239000000126 substance Substances 0.000 description 4
239000000758 substrate Substances 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
230000005747 tumor angiogenesis Effects 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
UYBWIEGTWASWSR-UHFFFAOYSA-N 1,3-diaminopropan-2-ol Chemical compound NCC(O)CN UYBWIEGTWASWSR-UHFFFAOYSA-N 0.000 description 3
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
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 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
GBUALRXLRRQXGH-UHFFFAOYSA-N 5-hydroxy-1,3-diazinane-2-thione Chemical compound OC1CNC(=S)NC1 GBUALRXLRRQXGH-UHFFFAOYSA-N 0.000 description 3
238000006418 Brown reaction Methods 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
101000797623 Homo sapiens Protein AMBP Proteins 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
208000037147 Hypercalcaemia Diseases 0.000 description 3
102400001240 Inter-alpha-trypsin inhibitor light chain 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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
239000003443 antiviral agent Substances 0.000 description 3
206010003230 arteritis Diseases 0.000 description 3
239000002585 base Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 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
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000000921 elemental analysis Methods 0.000 description 3
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
208000024693 gingival disease Diseases 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
230000000148 hypercalcaemia Effects 0.000 description 3
208000030915 hypercalcemia disease Diseases 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 3
239000010985 leather Substances 0.000 description 3
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 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
210000002997 osteoclast Anatomy 0.000 description 3
239000002245 particle Substances 0.000 description 3
230000008569 process Effects 0.000 description 3
230000004083 survival effect Effects 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
238000012546 transfer Methods 0.000 description 3
239000011701 zinc Substances 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 2
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
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 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-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
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
241000282412 Homo Species 0.000 description 2
108010001336 Horseradish Peroxidase Proteins 0.000 description 2
102100022337 Integrin alpha-V Human genes 0.000 description 2
102000012750 Membrane Glycoproteins Human genes 0.000 description 2
108010090054 Membrane Glycoproteins Proteins 0.000 description 2
QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-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
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
102000019997 adhesion receptor Human genes 0.000 description 2
108010013985 adhesion receptor Proteins 0.000 description 2
230000002776 aggregation Effects 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
230000003042 antagnostic effect Effects 0.000 description 2
239000004599 antimicrobial Substances 0.000 description 2
230000006907 apoptotic process Effects 0.000 description 2
108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
206010003246 arthritis Diseases 0.000 description 2
239000012131 assay buffer Substances 0.000 description 2
210000004204 blood vessel Anatomy 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000011575 calcium Substances 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
230000004709 cell invasion Effects 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
239000007979 citrate buffer Substances 0.000 description 2
150000004775 coumarins Chemical class 0.000 description 2
239000013078 crystal Substances 0.000 description 2
239000002178 crystalline material Substances 0.000 description 2
239000008367 deionised water Substances 0.000 description 2
229910021641 deionized water Inorganic materials 0.000 description 2
238000011161 development Methods 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
238000001035 drying Methods 0.000 description 2
238000010828 elution Methods 0.000 description 2
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 2
210000002744 extracellular matrix Anatomy 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
239000004023 fresh frozen plasma 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
206010020718 hyperplasia Diseases 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000011534 incubation Methods 0.000 description 2
238000002329 infrared spectrum Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
238000005342 ion exchange Methods 0.000 description 2
150000002596 lactones Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
230000033001 locomotion Effects 0.000 description 2
239000011777 magnesium Substances 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
230000036210 malignancy Effects 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
238000002156 mixing Methods 0.000 description 2
230000011164 ossification Effects 0.000 description 2
239000008188 pellet 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
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
230000003389 potentiating effect Effects 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000004044 response Effects 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 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
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-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
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical group O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-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
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 1
ZSZOYQQPFGTKJE-UHFFFAOYSA-N 3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]benzoic acid;hydrochloride Chemical compound Cl.C1C(O)CNC(NC=2C=C(C=C(O)C=2)C(O)=O)=N1 ZSZOYQQPFGTKJE-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
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
125000006847 BOC protecting group Chemical group 0.000 description 1
208000010392 Bone Fractures Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
102000008946 Fibrinogen Human genes 0.000 description 1
108010049003 Fibrinogen Proteins 0.000 description 1
241000287828 Gallus gallus Species 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
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 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
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
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
241000692870 Inachis io Species 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
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
206010029113 Neovascularisation Diseases 0.000 description 1
208000010191 Osteitis Deformans Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000027868 Paget disease Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241001494479 Pecora Species 0.000 description 1
238000003684 Perkin reaction Methods 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical class [P] OAICVXFJPJFONN-UHFFFAOYSA-N 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
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
241001061127 Thione Species 0.000 description 1
241000700605 Viruses Species 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
150000007513 acids Chemical class 0.000 description 1
238000005054 agglomeration Methods 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
150000005417 aminobenzoic acid derivatives Chemical class 0.000 description 1
SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 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
229940121375 antifungal agent Drugs 0.000 description 1
229940121357 antivirals Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
125000004429 atom Chemical group 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
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000008827 biological function Effects 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 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
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003795 chemical substances by application Substances 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
125000004122 cyclic group Chemical class 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
239000008121 dextrose Substances 0.000 description 1
125000006003 dichloroethyl group Chemical group 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
229920001971 elastomer Polymers 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
210000002889 endothelial cell Anatomy 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
229940012952 fibrinogen Drugs 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
238000011010 flushing procedure Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
238000009472 formulation Methods 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
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 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
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
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection 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
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000009545 invasion Effects 0.000 description 1
238000011835 investigation Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
150000002500 ions Chemical class 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
238000002955 isolation Methods 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
229910052745 lead Inorganic materials 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229920002521 macromolecule Polymers 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
208000027202 mammary Paget disease Diseases 0.000 description 1
239000003550 marker Substances 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
206010061289 metastatic neoplasm Diseases 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
ODKLEQPZOCJQMT-UHFFFAOYSA-N n,n-diethylpyridin-4-amine Chemical compound CCN(CC)C1=CC=NC=C1 ODKLEQPZOCJQMT-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 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
239000012299 nitrogen atmosphere Substances 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
230000003287 optical effect Effects 0.000 description 1
230000001599 osteoclastic 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
230000035515 penetration Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
208000028169 periodontal disease Diseases 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
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus 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
229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
229940116357 potassium thiocyanate Drugs 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001953 recrystallisation 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
238000013207 serial dilution 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
239000000377 silicon dioxide Substances 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000001509 sodium citrate Substances 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
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
239000011550 stock solution Substances 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
239000005720 sucrose Substances 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
150000003892 tartrate salts Chemical class 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
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
230000000699 topical effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
229940038773 trisodium citrate Drugs 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000012224 working solution 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)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Rheumatology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Epidemiology (AREA)
Cardiology (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Molecular Biology (AREA)
Pain & Pain Management (AREA)
Heart & Thoracic Surgery (AREA)
Oncology (AREA)
Immunology (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)

NO20004316A 1998-03-04 2000-08-30 Meta azasykliske aminobenzosyreforbindelser og derivater derav som er integrinatantagonister NO315703B1 (no)

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 (3)

Publication Number	Publication Date
NO20004316D0 NO20004316D0 (no)	2000-08-30
NO20004316L NO20004316L (no)	2000-11-06
NO315703B1 true NO315703B1 (no)	2003-10-13

Family

ID=21875345

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20004316A NO315703B1 (no)	1998-03-04	2000-08-30	Meta azasykliske aminobenzosyreforbindelser og derivater derav som er integrinatantagonister

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
JP2003531141A (ja)	2000-04-17	2003-10-21	セルテックアールアンドディリミテッド	エナミン誘導体
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
JP2004505110A (ja)	2000-08-02	2004-02-19	セルテック　アール　アンド　ディ　リミテッド	３位置換イソキノリン−１−イル誘導体
AU2003299600A1 (en) *	2002-12-20	2004-07-29	Pharmacia Corpration	The r-isomer of beta amino acid compounds as integrin receptor antagonists derivatives
UA87854C2 (en)	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
BRPI0611814A2 (pt) *	2005-06-10	2008-12-09	Bipar Sciences Inc	moduladores parp e tratamento de cÂnceres
CN101687040A (zh)	2007-03-01	2010-03-31	马林克罗特公司	整合光活性的小分子及其用途
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
US8716226B2 (en)	2012-07-18	2014-05-06	Saint Louis University	3,5 phenyl-substituted beta amino acid derivatives as integrin antagonists
IN2015DN00099A (is)	2012-07-18	2015-05-29	Univ Saint Louis
WO2015181676A1 (en)	2014-05-30	2015-12-03	Pfizer Inc.	Carbonitrile derivatives as selective androgen receptor modulators
WO2015187774A1 (en) *	2014-06-04	2015-12-10	Monsanto Technology Llc	3,6-dichlorosalicylic acid compounds and related synthetic processes
CN108779077A (zh)	2015-12-30	2018-11-09	圣路易斯大学	作为pan整合素拮抗剂的间位氮杂环氨基苯甲酸衍生物
CA3182964A1 (en)	2020-05-14	2021-11-18	Ube Corporation	1,4,5,6-tetrahydropyrimidin-2-amine derivative
WO2023275715A1 (en)	2021-06-30	2023-01-05	Pfizer Inc.	Metabolites of selective androgen receptor modulators
JPWO2023085396A1 (is)	2021-11-12	2023-05-19

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CZ293323B6 (cs) *	1995-08-30	2004-04-14	G. D. Searle & Co.	Meta-guanidinové, močovinové, thiomočovinové nebo azacyklické deriváty aminobenzoové kyseliny jako antagonisty integrinů

1999
- 1999-02-11 ZA ZA9904406A patent/ZA994406B/xx unknown
- 1999-02-22 YU YU52000A patent/YU52000A/sh unknown
- 1999-02-22 TR TR2000/02542T patent/TR200002542T2/xx unknown
- 1999-02-22 EP EP99937927A patent/EP1060164A1/en active Pending
- 1999-02-22 GE GEAP19995537A patent/GEP20033118B/en unknown
- 1999-02-22 BR BR9908470-8A patent/BR9908470A/pt not_active Application Discontinuation
- 1999-02-22 HU HU0100865A patent/HUP0100865A3/hu unknown
- 1999-02-22 JP JP2000534538A patent/JP2002505323A/ja active Pending
- 1999-02-22 AU AU32947/99A patent/AU753230B2/en not_active Ceased
- 1999-02-22 SK SK1300-2000A patent/SK13002000A3/sk unknown
- 1999-02-22 CA CA002322207A patent/CA2322207A1/en not_active Abandoned
- 1999-02-22 EA EA200000804A patent/EA200000804A1/ru unknown
- 1999-02-22 OA OA1200000238A patent/OA11530A/en unknown
- 1999-02-22 EE EEP200000506A patent/EE200000506A/xx unknown
- 1999-02-22 IL IL13765399A patent/IL137653A0/xx unknown
- 1999-02-22 PL PL99342726A patent/PL342726A1/xx unknown
- 1999-02-22 UA UA2000095148A patent/UA71906C2/uk unknown
- 1999-02-22 CN CNB998035815A patent/CN1214011C/zh not_active Expired - Fee Related
- 1999-02-22 AP APAP/P/2000/001893A patent/AP1244A/en active
- 1999-02-22 NZ NZ506598A patent/NZ506598A/en unknown
- 1999-02-22 WO PCT/US1999/003281 patent/WO1999044994A1/en not_active Ceased
- 1999-02-22 KR KR1020007009774A patent/KR20010041584A/ko not_active Ceased
- 1999-02-22 HR HR20000574A patent/HRP20000574A2/hr not_active Application Discontinuation
- 1999-02-22 ID IDW20001695A patent/ID25591A/id 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
SK13002000A3 (sk)	2001-07-10
EA200000804A1 (ru)	2001-04-23
CN1214011C (zh)	2005-08-10
YU52000A (sh)	2003-02-28
AR018139A1 (es)	2001-10-31
MY123908A (en)	2006-06-30
HRP20000574A2 (en)	2001-08-31
CN1291978A (zh)	2001-04-18
NZ506598A (en)	2003-07-25
NO20004316L (no)	2000-11-06
CA2322207A1 (en)	1999-09-10
GEP20033118B (en)	2003-11-25
IL137653A0 (en)	2001-10-31
TR200002542T2 (tr)	2001-05-21
OA11530A (en)	2004-05-17
JP2002505323A (ja)	2002-02-19
AP1244A (en)	2004-02-04
IS5582A (is)	2000-08-04
AU3294799A (en)	1999-09-20
ID25591A (id)	2000-10-19
EE200000506A (et)	2002-04-15
NO20004316D0 (no)	2000-08-30
AU753230B2 (en)	2002-10-10
HUP0100865A3 (en)	2001-11-28
PL342726A1 (en)	2001-07-02
UA71906C2 (en)	2005-01-17
KR20010041584A (ko)	2001-05-25
WO1999044994A1 (en)	1999-09-10
ZA994406B (en)	2000-02-11
HUP0100865A2 (hu)	2001-08-28
EP1060164A1 (en)	2000-12-20
BG104740A (en)	2001-02-28
BR9908470A (pt)	2000-12-05
AP2000001893A0 (en)	2000-09-30

Publication	Publication Date	Title
NO315703B1 (no)	2003-10-13	Meta azasykliske aminobenzosyreforbindelser og derivater derav som er integrinatantagonister
CA2250586C (en)	2007-04-17	Meta-substituted phenylene sulphonamide derivatives
AU765294B2 (en)	2003-09-11	Heterocyclic glycyl beta-alanine derivatives as vitronectin antagonists
EP0889875B1 (en)	2001-06-20	Cyclopropyl alkanoic acid derivatives
JP2000515493A (ja)	2000-11-21	パラ―置換フェニレン誘導体
US6372719B1 (en)	2002-04-16	ανβ3 integrin antagonists in combination with chemotherapeutic agents
MXPA05006732A (es)	2005-09-08	El isomero r de compuesto de beta-aminoacido como derivados de antagonistas de receptor de la integrina.
US6013651A (en)	2000-01-11	Meta-azacyclic amino benzoic acid compounds and derivatives thereof
US6689754B1 (en)	2004-02-10	Heterocyclic glycyl β-alanine derivatives
US6172256B1 (en)	2001-01-09	Chiral-β-amino acid compounds and derivatives thereof
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
US20080064716A1 (en)	2008-03-13	Biphenyl Integrin Antagonists
MXPA00009967A (en)	2001-07-31	Heterocyclic glycyl beta-alanine derivatives as vitronectin antagonists

Legal Events

Date	Code	Title	Description
2005-10-10	MM1K	Lapsed by not paying the annual fees