LV11429B - Tricyclopolyazamacrocyclophosphonic acids, complexes and derivates thereof, for use as contrast agents - Google Patents
Tricyclopolyazamacrocyclophosphonic acids, complexes and derivates thereof, for use as contrast agents Download PDFInfo
- Publication number
- LV11429B LV11429B LVP-95-361A LV950361A LV11429B LV 11429 B LV11429 B LV 11429B LV 950361 A LV950361 A LV 950361A LV 11429 B LV11429 B LV 11429B
- Authority
- LV
- Latvia
- Prior art keywords
- formula
- compound
- alkyl
- complex
- pharmaceutically acceptable
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims abstract description 27
- 239000002872 contrast media Substances 0.000 title abstract 2
- 150000007513 acids Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 82
- 229910052757 nitrogen Inorganic materials 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 44
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 238000010992 reflux Methods 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- -1 bromoacetamido Chemical group 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 241001465754 Metazoa Species 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 239000011149 active material Substances 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 3
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 claims 3
- 150000002540 isothiocyanates Chemical class 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 claims 3
- TTZMPOZCBFTTPR-UHFFFAOYSA-N O=P1OCO1 Chemical compound O=P1OCO1 TTZMPOZCBFTTPR-UHFFFAOYSA-N 0.000 claims 2
- 125000004494 ethyl ester group Chemical group 0.000 claims 2
- 229910021645 metal ion Inorganic materials 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Chemical group 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 150000002500 ions Chemical class 0.000 abstract description 17
- 229910052742 iron Inorganic materials 0.000 abstract description 5
- 229910052688 Gadolinium Inorganic materials 0.000 abstract description 4
- 229910052748 manganese Inorganic materials 0.000 abstract description 4
- 238000001727 in vivo Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 27
- 210000000988 bone and bone Anatomy 0.000 description 25
- 239000003446 ligand Substances 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 15
- 230000005298 paramagnetic effect Effects 0.000 description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000013522 chelant Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 210000004185 liver Anatomy 0.000 description 10
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 230000005291 magnetic effect Effects 0.000 description 9
- 229910001868 water Inorganic materials 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 8
- 239000011572 manganese Substances 0.000 description 8
- 210000003205 muscle Anatomy 0.000 description 8
- 210000000952 spleen Anatomy 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000003513 alkali Substances 0.000 description 5
- 230000001588 bifunctional effect Effects 0.000 description 5
- 235000019256 formaldehyde Nutrition 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 230000010412 perfusion Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000002429 large intestine Anatomy 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 210000000813 small intestine Anatomy 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000010668 complexation reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
- 229910018828 PO3H2 Inorganic materials 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000012614 Q-Sepharose Substances 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 238000005341 cation exchange Methods 0.000 description 2
- 239000003518 caustics Substances 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 2
- 239000011268 mixed slurry Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical group [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 150000000921 Gadolinium Chemical class 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid group Chemical class C(C=CC1=CC=CC=C1)(=O)O WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 238000010549 co-Evaporation Methods 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 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
- 235000019441 ethanol Nutrition 0.000 description 1
- PHTXVQQRWJXYPP-UHFFFAOYSA-N ethyltrifluoromethylaminoindane Chemical compound C1=C(C(F)(F)F)C=C2CC(NCC)CC2=C1 PHTXVQQRWJXYPP-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 150000004820 halides Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000001184 hypocalcaemic effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UIWOZHBYBSGCOS-UHFFFAOYSA-N methoxy(oxido)phosphanium Chemical class CO[PH2]=O UIWOZHBYBSGCOS-UHFFFAOYSA-N 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- QVRVXSZKCXFBTE-UHFFFAOYSA-N n-[4-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)butyl]-2-(2-fluoroethoxy)-5-methylbenzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCCCNC(=O)C1=CC(C)=CC=C1OCCF QVRVXSZKCXFBTE-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 150000002976 peresters Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical class [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000079 presaturation Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002455 scale inhibitor Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-N sorbic acid group Chemical group C(\C=C\C=C\C)(=O)O WSWCOQWTEOXDQX-MQQKCMAXSA-N 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- BGRJTUBHPOOWDU-UHFFFAOYSA-N sulpiride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
- G01R33/281—Means for the use of in vitro contrast agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Luminescent Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/058,622 US5385893A (en) | 1993-05-06 | 1993-05-06 | Tricyclopolyazamacrocyclophosphonic acids, complexes and derivatives thereof, for use as contrast agents |
| PCT/US1994/005071 WO1994026276A1 (en) | 1993-05-06 | 1994-05-06 | Tricyclopolyazamacrocyclophosphonic acids, complexes and derivatives thereof, for use as contrast agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LV11429A LV11429A (lv) | 1996-08-20 |
| LV11429B true LV11429B (en) | 1997-04-20 |
Family
ID=22017946
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LVP-95-361A LV11429B (en) | 1993-05-06 | 1995-12-06 | Tricyclopolyazamacrocyclophosphonic acids, complexes and derivates thereof, for use as contrast agents |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5385893A (de) |
| EP (1) | EP0697872B1 (de) |
| JP (1) | JP3553940B2 (de) |
| KR (1) | KR960702462A (de) |
| CN (1) | CN1125906A (de) |
| AT (1) | ATE316377T1 (de) |
| AU (1) | AU687400B2 (de) |
| BG (1) | BG100194A (de) |
| CA (1) | CA2162172A1 (de) |
| DE (1) | DE69434618T2 (de) |
| FI (1) | FI955336A (de) |
| HU (1) | HUT72649A (de) |
| LV (1) | LV11429B (de) |
| NO (1) | NO954441L (de) |
| PL (1) | PL311649A1 (de) |
| SG (1) | SG46496A1 (de) |
| WO (1) | WO1994026276A1 (de) |
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| US5645818A (en) * | 1989-03-24 | 1997-07-08 | Guerbet S.A. | Diagnostic compositions comprising a complex formed by a nitrogenous macrocyclic ligand with metal ions |
| US5739294A (en) * | 1991-12-10 | 1998-04-14 | The Dow Chemical Company | Bicyclopol yazamacrocyclophosphonic acid complexes for use as contrast agents |
| US5714604A (en) * | 1993-05-06 | 1998-02-03 | The Dow Chemical Company | Process for the preparation of azamacrocyclic or acyclic aminophosphonate ester derivatives |
| US5672335A (en) * | 1994-11-30 | 1997-09-30 | Schering Aktiengesellschaft | Use of metal complexes as liver and gallbladder X-ray diagnostic agents |
| US6207826B1 (en) * | 1995-03-27 | 2001-03-27 | Isis Pharmaceuticals, Inc. | Macrocyclic compounds having nitrogen-containing linkages |
| US6107482A (en) * | 1995-03-27 | 2000-08-22 | Isis Pharmaceuticals, Inc. | Nitrogenous macrocyclic compounds |
| DE19546234C1 (de) * | 1995-12-04 | 1997-08-28 | Schering Ag | Neue makrobicyclische Verbindungen, Verfahren zu ihrer Herstellung und diese makrobicyclischen Verbindungen enthaltende pharmazeutische Mittel |
| US5834456A (en) * | 1996-02-23 | 1998-11-10 | The Dow Chemical Company | Polyazamacrocyclofluoromonoalkylphosphonic acids, and their complexes, for use as contrast agents |
| CA2251924C (en) * | 1996-04-19 | 2006-05-30 | The Dow Chemical Company | Fluorescent chelates as visual tissue specific imaging agents |
| DE69906732T2 (de) * | 1998-06-15 | 2003-10-16 | Unilever N.V., Rotterdam | Bleichkatalysatoren und sie enthaltende formulierungen |
| AU1092601A (en) * | 1999-10-18 | 2001-04-30 | Dow Global Technologies Inc. | Aminoalkylenephosphonates for treatment of bone disorders |
| US6794371B1 (en) * | 1999-10-18 | 2004-09-21 | The Dow Chemical Company | Aminoalkylenephosphonates for treatment of bone disorders |
| EP1778699A4 (de) * | 2004-08-10 | 2009-02-25 | Dow Global Technologies Inc | Targeting von chelanten und chelaten |
| US20100111856A1 (en) | 2004-09-23 | 2010-05-06 | Herman Gill | Zirconium-radiolabeled, cysteine engineered antibody conjugates |
| KR101270829B1 (ko) | 2004-09-23 | 2013-06-07 | 제넨테크, 인크. | 시스테인 유전자조작 항체 및 접합체 |
| MX2008015132A (es) | 2006-05-30 | 2008-12-10 | Genentech Inc | Anticuerpos e inmunoconjugados y sus usos. |
| PL2845866T3 (pl) | 2006-10-27 | 2017-10-31 | Genentech Inc | Przeciwciała i immunokoniugaty oraz ich zastosowanie |
| WO2008100805A2 (en) | 2007-02-09 | 2008-08-21 | Genentech, Inc. | Anti-robo4 antibodies and uses therefor |
| PL2474557T3 (pl) | 2007-07-16 | 2015-02-27 | Genentech Inc | Przeciwciała anty- CD79b i immunokoniugaty i sposoby stosowania |
| KR101559595B1 (ko) | 2007-07-16 | 2015-10-12 | 제넨테크, 인크. | 인간화 항-ｃｄ７９ｂ 항체 및 면역접합체 및 사용 방법 |
| IL295449A (en) | 2008-01-31 | 2022-10-01 | Genentech Inc | and fusion antibody-drug-cd79b engineered antibodies cysteine- |
| JP6132548B2 (ja) | 2009-04-01 | 2017-05-24 | ジェネンテック， インコーポレイテッド | 抗ＦｃＲＨ５抗体および免疫接合体および使用方法 |
| AU2010256410B2 (en) | 2009-06-04 | 2016-10-20 | Massachusetts Institute Of Technology | Methods for identification of sites for IgG conjugation |
| CN102510774B (zh) * | 2009-09-18 | 2014-07-23 | 科莱恩金融(Bvi)有限公司 | 制备桥联的三氮杂环壬烷的锰络合物的方法 |
| RU2580038C2 (ru) | 2009-12-04 | 2016-04-10 | Дженентек, Инк. | Мультиспецифические антитела, аналоги антител, композиции и способы |
| MX336109B (es) | 2010-06-03 | 2016-01-08 | Genentech Inc | Formacion de imagenes inmuno-tep de anticuerpos e inmunoconjugados y usos de lo mismo. |
| RU2755066C2 (ru) | 2010-06-08 | 2021-09-13 | Дженентек, Инк. | Полученные с помощью генной инженерии антитела с цистеиновыми заменами и их конъюгаты |
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| WO2017167712A1 (en) | 2016-03-30 | 2017-10-05 | F. Hoffmann-La Roche Ag | Improved sortase |
| KR102495650B1 (ko) | 2017-04-12 | 2023-02-02 | 에프. 호프만-라 로슈 아게 | 알데히드 함유 표적 분자의 라벨링 방법 |
| EP3652214A1 (de) | 2017-07-13 | 2020-05-20 | H. Hoffnabb-La Roche Ag | Neues bindemittel und assay für pivka |
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| WO2019175131A1 (en) | 2018-03-14 | 2019-09-19 | F. Hoffmann-La Roche Ag | Method for affinity maturation of antibodies |
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| WO2020069433A1 (en) | 2018-09-28 | 2020-04-02 | Imaginab, Inc. | Cd8 imaging constructs and methods of use thereof |
| KR20220016210A (ko) | 2019-07-22 | 2022-02-08 | 에프. 호프만-라 로슈 아게 | 자궁내막증의 비-침습적 진단용 혈액 생물표지자로써 s100a9 |
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| BR112022001140A2 (pt) | 2019-07-22 | 2022-03-15 | Hoffmann La Roche | Métodos para avaliar se um paciente tem endometriose ou está em risco de desenvolver endometriose, selecionar um paciente para terapia e monitorar um paciente que sofre de endometriose ou que está sendo tratado para endometriose |
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| CN116457660A (zh) | 2020-10-30 | 2023-07-18 | 豪夫迈·罗氏有限公司 | Timp1作为胆管癌的标志物 |
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| WO2023072904A1 (en) | 2021-10-26 | 2023-05-04 | F. Hoffmann-La Roche Ag | Monoclonal antibodies specific for sars-cov-2 rbd |
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| WO2023131594A1 (en) | 2022-01-05 | 2023-07-13 | F. Hoffmann-La Roche Ag | Derivatization of compounds in patient samples for therapeutic drug monitoring (tdm) |
| WO2023247752A1 (en) | 2022-06-23 | 2023-12-28 | F. Hoffmann-La Roche Ag | Method for diagnosing endometriosis and for classifying the stage of endometriosis |
| WO2024017983A1 (en) | 2022-07-22 | 2024-01-25 | F. Hoffmann-La Roche Ag | Meteorin-like protein (metrnl) as (blood) biomarker for the diagnosis of polycystic ovarian syndrome |
| WO2024017982A1 (en) | 2022-07-22 | 2024-01-25 | F. Hoffmann-La Roche Ag | Leukotriene a4 hydrolase (lta4h) as (blood) biomarker for the diagnosis of polycystic ovarian syndrome |
| WO2024017985A1 (en) | 2022-07-22 | 2024-01-25 | F. Hoffmann-La Roche Ag | Fibroblast growth factor binding protein 1 (fgfbp1) as (blood) biomarker for the diagnosis of polycystic ovarian syndrome |
| WO2025026908A1 (en) | 2023-07-28 | 2025-02-06 | Roche Diagnostics Gmbh | Serum epha1 as biomarker for endometriosis |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2609390A (en) * | 1950-06-01 | 1952-09-02 | Frederick C Bersworth | Phosphonic alkylene polyamino acids and method of producing same |
| US3336221A (en) * | 1964-11-05 | 1967-08-15 | Calgon Corp | Method of inhibiting precipitation and scale formation |
| US3331773A (en) * | 1966-07-22 | 1967-07-18 | Grace W R & Co | Process for inhibiting precipitation in water |
| US3434969A (en) * | 1967-08-11 | 1969-03-25 | Calgon Corp | Scale inhibiting |
| GB1441081A (en) * | 1974-01-09 | 1976-06-30 | Ici Ltd | Tetra-aza-macrocycles and their metal complexes |
| US4980148A (en) * | 1985-02-06 | 1990-12-25 | Mallinckrodt, Inc. | Methods for enhancing magnetic resonance imaging |
| US4880008A (en) * | 1985-05-08 | 1989-11-14 | The General Hospital Corporation | Vivo enhancement of NMR relaxivity |
| US4899755A (en) * | 1985-05-08 | 1990-02-13 | The General Hospital Corporation | Hepatobiliary NMR contrast agents |
| DE3825040A1 (de) * | 1988-07-20 | 1990-01-25 | Schering Ag, 13353 Berlin | 5- oder 6-ring- enthaltende makrocyclische polyaza-verbindungen, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel |
| US5247077A (en) * | 1989-06-23 | 1993-09-21 | Celltech Limited | Tri-aza macrocycles and processes for their preparation |
| ATE160943T1 (de) * | 1991-12-10 | 1997-12-15 | Dow Chemical Co | Bicycloazamakrocyclophosphon-säure, komplexe, konjugate, kontrastmittel und herstellung |
| HU9302308D0 (en) * | 1991-12-10 | 1993-12-28 | Dow Chemical Co | Process for production lof biciclo-polyaza-macrocyclyc-carbonic acid-complexes and their conjugates and of medical preparatives containing them |
| US5428139A (en) * | 1991-12-10 | 1995-06-27 | The Dow Chemical Company | Bicyclopolyazamacrocyclophosphonic acid complexes for use as radiopharmaceuticals |
| AU3415493A (en) * | 1991-12-10 | 1993-07-19 | Dow Chemical Company, The | Bicycle-polyazamacrocyclocarboxylic acid complexes, conjugates, preparation and use as contrast agents |
-
1993
- 1993-05-06 US US08/058,622 patent/US5385893A/en not_active Expired - Lifetime
-
1994
- 1994-05-06 AT AT94916043T patent/ATE316377T1/de not_active IP Right Cessation
- 1994-05-06 AU AU67849/94A patent/AU687400B2/en not_active Ceased
- 1994-05-06 SG SG1996005135A patent/SG46496A1/en unknown
- 1994-05-06 PL PL94311649A patent/PL311649A1/xx unknown
- 1994-05-06 CN CN94192528A patent/CN1125906A/zh active Pending
- 1994-05-06 WO PCT/US1994/005071 patent/WO1994026276A1/en active IP Right Grant
- 1994-05-06 HU HU9502023A patent/HUT72649A/hu unknown
- 1994-05-06 KR KR1019950704947A patent/KR960702462A/ko not_active Application Discontinuation
- 1994-05-06 JP JP52558694A patent/JP3553940B2/ja not_active Expired - Fee Related
- 1994-05-06 CA CA002162172A patent/CA2162172A1/en not_active Abandoned
- 1994-05-06 EP EP94916043A patent/EP0697872B1/de not_active Expired - Lifetime
- 1994-05-06 DE DE69434618T patent/DE69434618T2/de not_active Expired - Fee Related
-
1995
- 1995-11-06 FI FI955336A patent/FI955336A/fi unknown
- 1995-11-06 NO NO954441A patent/NO954441L/no unknown
- 1995-12-05 BG BG100194A patent/BG100194A/xx unknown
- 1995-12-06 LV LVP-95-361A patent/LV11429B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| LV11429A (lv) | 1996-08-20 |
| WO1994026276A1 (en) | 1994-11-24 |
| EP0697872A1 (de) | 1996-02-28 |
| JPH08511003A (ja) | 1996-11-19 |
| US5385893A (en) | 1995-01-31 |
| DE69434618D1 (de) | 2006-04-13 |
| FI955336A (fi) | 1995-12-22 |
| EP0697872B1 (de) | 2006-01-25 |
| AU687400B2 (en) | 1998-02-26 |
| ATE316377T1 (de) | 2006-02-15 |
| KR960702462A (ko) | 1996-04-27 |
| NO954441D0 (no) | 1995-11-06 |
| CA2162172A1 (en) | 1994-11-24 |
| NO954441L (no) | 1996-01-05 |
| DE69434618T2 (de) | 2006-08-10 |
| BG100194A (en) | 1996-12-31 |
| PL311649A1 (en) | 1996-03-04 |
| EP0697872A4 (de) | 2003-04-02 |
| HUT72649A (en) | 1996-05-28 |
| SG46496A1 (en) | 1998-02-20 |
| FI955336A0 (fi) | 1995-11-06 |
| AU6784994A (en) | 1994-12-12 |
| HU9502023D0 (en) | 1995-09-28 |
| CN1125906A (zh) | 1996-07-03 |
| JP3553940B2 (ja) | 2004-08-11 |
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