NO860981L - Radiografisk middel. - Google Patents

Radiografisk middel.

Info

Publication number: NO860981L
Authority: NO; Norway
Prior art keywords: formula; stated; alkyl; compound; group
Prior art date: 1984-07-19

Application number

NO860981A

Other languages

English (en)

Norwegian (no)

Inventor

Nicholas S Bodor

Original Assignee

Univ Florida

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.)

1984-07-19

Filing date

1986-03-14

Publication date

1986-05-20

1986-03-14 Application filed by Univ Florida filed Critical Univ Florida

1986-05-20 Publication of NO860981L publication Critical patent/NO860981L/no

Links

238000000034 method Methods 0.000 claims abstract description 178
239000002738 chelating agent Substances 0.000 claims abstract description 164
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 49
210000004556 brain Anatomy 0.000 claims abstract description 48
125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims abstract description 37
239000000203 mixture Substances 0.000 claims abstract description 36
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 34
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 34
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims abstract description 18
238000001727 in vivo Methods 0.000 claims abstract description 16
230000003647 oxidation Effects 0.000 claims abstract description 16
238000007254 oxidation reaction Methods 0.000 claims abstract description 16
239000000126 substance Substances 0.000 claims abstract description 15
230000008499 blood brain barrier function Effects 0.000 claims abstract description 12
125000005462 imide group Chemical group 0.000 claims abstract description 8
210000001218 blood-brain barrier Anatomy 0.000 claims abstract description 7
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 299
239000012217 radiopharmaceutical Substances 0.000 claims description 123
229940121896 radiopharmaceutical Drugs 0.000 claims description 123
230000002799 radiopharmaceutical effect Effects 0.000 claims description 123
125000002947 alkylene group Chemical group 0.000 claims description 113
125000000217 alkyl group Chemical group 0.000 claims description 93
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 89
150000003839 salts Chemical class 0.000 claims description 83
229910052739 hydrogen Inorganic materials 0.000 claims description 78
229910052751 metal Inorganic materials 0.000 claims description 60
239000002184 metal Substances 0.000 claims description 60
125000000524 functional group Chemical group 0.000 claims description 59
-1 amino, carboxyl Chemical group 0.000 claims description 53
230000006870 function Effects 0.000 claims description 49
229910052799 carbon Inorganic materials 0.000 claims description 41
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical group C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 41
150000001413 amino acids Chemical class 0.000 claims description 40
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 39
230000002829 reductive effect Effects 0.000 claims description 37
238000002360 preparation method Methods 0.000 claims description 34
150000001408 amides Chemical class 0.000 claims description 31
125000004430 oxygen atom Chemical group O* 0.000 claims description 31
125000004432 carbon atom Chemical group C* 0.000 claims description 29
239000002253 acid Substances 0.000 claims description 28
239000013522 chelant Substances 0.000 claims description 27
230000002285 radioactive effect Effects 0.000 claims description 27
150000001450 anions Chemical class 0.000 claims description 26
230000008569 process Effects 0.000 claims description 26
239000003638 chemical reducing agent Substances 0.000 claims description 25
125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 claims description 25
230000009467 reduction Effects 0.000 claims description 24
125000001424 substituent group Chemical group 0.000 claims description 24
125000001188 haloalkyl group Chemical group 0.000 claims description 22
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 18
235000000346 sugar Nutrition 0.000 claims description 18
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 17
150000002500 ions Chemical class 0.000 claims description 17
238000003384 imaging method Methods 0.000 claims description 16
150000003949 imides Chemical class 0.000 claims description 16
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 16
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
239000007858 starting material Substances 0.000 claims description 14
IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical group C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 claims description 13
238000004519 manufacturing process Methods 0.000 claims description 13
229910052713 technetium Inorganic materials 0.000 claims description 13
GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical group [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 claims description 13
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 12
150000007522 mineralic acids Chemical class 0.000 claims description 12
150000007524 organic acids Chemical class 0.000 claims description 12
125000006239 protecting group Chemical group 0.000 claims description 12
239000012736 aqueous medium Substances 0.000 claims description 11
125000003710 aryl alkyl group Chemical group 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 claims description 10
231100000252 nontoxic Toxicity 0.000 claims description 10
230000003000 nontoxic effect Effects 0.000 claims description 10
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical group [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 claims description 10
229940056501 technetium 99m Drugs 0.000 claims description 9
230000000536 complexating effect Effects 0.000 claims description 8
238000005956 quaternization reaction Methods 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
238000010668 complexation reaction Methods 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
125000002541 furyl group Chemical group 0.000 claims description 7
125000004423 acyloxy group Chemical group 0.000 claims description 6
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
230000007935 neutral effect Effects 0.000 claims description 5
230000005855 radiation Effects 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
239000002585 base Substances 0.000 claims description 3
239000003153 chemical reaction reagent Substances 0.000 claims description 3
230000009918 complex formation Effects 0.000 claims description 3
AWJUIBRHMBBTKR-UHFFFAOYSA-O isoquinolin-2-ium Chemical group C1=[NH+]C=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-O 0.000 claims description 3
230000001934 delay Effects 0.000 claims description 2
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 4
SMWDFEZZVXVKRB-UHFFFAOYSA-O hydron;quinoline Chemical group [NH+]1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-O 0.000 claims 4
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
125000005115 alkyl carbamoyl group Chemical group 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
239000000243 solution Substances 0.000 description 90
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 82
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 81
238000006243 chemical reaction Methods 0.000 description 72
150000002148 esters Chemical class 0.000 description 61
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
ZBSGKPYXQINNGF-UHFFFAOYSA-N N-nicotinoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CN=C1 ZBSGKPYXQINNGF-UHFFFAOYSA-N 0.000 description 51
235000001968 nicotinic acid Nutrition 0.000 description 41
239000011664 nicotinic acid Substances 0.000 description 41
229960003512 nicotinic acid Drugs 0.000 description 39
239000000047 product Substances 0.000 description 38
239000002243 precursor Substances 0.000 description 37
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
150000003254 radicals Chemical group 0.000 description 32
239000002904 solvent Substances 0.000 description 32
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 30
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 28
238000005481 NMR spectroscopy Methods 0.000 description 28
239000003814 drug Substances 0.000 description 28
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
238000001914 filtration Methods 0.000 description 27
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 26
150000008064 anhydrides Chemical class 0.000 description 25
238000006722 reduction reaction Methods 0.000 description 25
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
229940024606 amino acid Drugs 0.000 description 24
235000001014 amino acid Nutrition 0.000 description 24
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
229940079593 drug Drugs 0.000 description 20
239000002244 precipitate Substances 0.000 description 19
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
150000001412 amines Chemical class 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 17
239000007822 coupling agent Substances 0.000 description 16
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 16
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
239000004471 Glycine Substances 0.000 description 14
238000010992 reflux Methods 0.000 description 13
DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 11
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
229910052943 magnesium sulfate Inorganic materials 0.000 description 10
235000019341 magnesium sulphate Nutrition 0.000 description 10
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 10
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 9
239000003446 ligand Substances 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
238000002390 rotary evaporation Methods 0.000 description 9
230000002459 sustained effect Effects 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
230000004087 circulation Effects 0.000 description 8
238000001816 cooling Methods 0.000 description 8
238000001212 derivatisation Methods 0.000 description 8
MCVMLYSLPCECGO-UHFFFAOYSA-N isoquinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CN=CC2=C1 MCVMLYSLPCECGO-UHFFFAOYSA-N 0.000 description 8
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210000000056 organ Anatomy 0.000 description 8
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239000000843 powder Substances 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
239000007787 solid Substances 0.000 description 8
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 7
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230000003511 endothelial effect Effects 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
LCFXLZAXGXOXAP-QPJJXVBHSA-N ethyl (2e)-2-cyano-2-hydroxyiminoacetate Chemical compound CCOC(=O)C(=N\O)\C#N LCFXLZAXGXOXAP-QPJJXVBHSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
125000003916 ethylene diamine group Chemical group 0.000 description 1
238000000605 extraction Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
229960002598 fumaric acid Drugs 0.000 description 1
229940006110 gallium-67 Drugs 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
229960002442 glucosamine Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
230000036541 health Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
GEOVEUCEIQCBKH-UHFFFAOYSA-N hypoiodous acid Chemical compound IO GEOVEUCEIQCBKH-UHFFFAOYSA-N 0.000 description 1
NBZBKCUXIYYUSX-UHFFFAOYSA-N iminodiacetic acid Chemical class OC(=O)CNCC(O)=O NBZBKCUXIYYUSX-UHFFFAOYSA-N 0.000 description 1
230000006872 improvement Effects 0.000 description 1
229940055742 indium-111 Drugs 0.000 description 1
APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
238000001802 infusion Methods 0.000 description 1
XAAKCCMYRKZRAK-UHFFFAOYSA-N isoquinoline-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NC=CC2=C1 XAAKCCMYRKZRAK-UHFFFAOYSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
125000005647 linker group Chemical group 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
230000007774 longterm Effects 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
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000009061 membrane transport Effects 0.000 description 1
230000006883 memory enhancing effect Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
IVEWREUSOKDILU-UHFFFAOYSA-N n-(2-aminoacetyl)pyridine-2-carboxamide Chemical class NCC(=O)NC(=O)C1=CC=CC=N1 IVEWREUSOKDILU-UHFFFAOYSA-N 0.000 description 1
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000012430 organic reaction media Substances 0.000 description 1
150000002923 oximes Chemical group 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
230000000149 penetrating effect Effects 0.000 description 1
230000035515 penetration Effects 0.000 description 1
229960001639 penicillamine Drugs 0.000 description 1
230000003836 peripheral circulation Effects 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000007793 ph indicator Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
125000005545 phthalimidyl group Chemical group 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229940075930 picrate Drugs 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
229940079877 pyrogallol Drugs 0.000 description 1
LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical class [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 1
UKHWJBVVWVYFEY-UHFFFAOYSA-M silver;hydroxide Chemical compound [OH-].[Ag+] UKHWJBVVWVYFEY-UHFFFAOYSA-M 0.000 description 1
235000021309 simple sugar Nutrition 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000003270 steroid hormone Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
229950000244 sulfanilic acid Drugs 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
231100000057 systemic toxicity Toxicity 0.000 description 1
125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003495 technetium Chemical class 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical class [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000032258 transport Effects 0.000 description 1
239000002023 wood Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/40—2,5-Pyrrolidine-diones
- C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Optics & Photonics (AREA)
Animal Behavior & Ethology (AREA)
Biophysics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Physics & Mathematics (AREA)
Biochemistry (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Genetics & Genomics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)
Quinoline Compounds (AREA)

NO860981A 1984-07-19 1986-03-14 Radiografisk middel. NO860981L (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US63231484A	1984-07-19	1984-07-19

Publications (1)

Publication Number	Publication Date
NO860981L true NO860981L (no)	1986-05-20

Family

ID=24535023

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO860981A NO860981L (no)	1984-07-19	1986-03-14	Radiografisk middel.

Country Status (13)

Country	Link
EP (1)	EP0187832A1 (mo)
JP (1)	JPS61106556A (mo)
KR (1)	KR900007514B1 (mo)
AU (1)	AU4635885A (mo)
CA (1)	CA1267899A (mo)
DK (1)	DK124786A (mo)
ES (1)	ES8704900A1 (mo)
FI (1)	FI861118A0 (mo)
GR (1)	GR851792B (mo)
NO (1)	NO860981L (mo)
PT (1)	PT80841B (mo)
WO (1)	WO1986000898A1 (mo)
ZA (1)	ZA855476B (mo)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5079366A (en) *	1987-04-07	1992-01-07	University Of Florida	Quarternary pyridinium salts
US4888427A (en) *	1987-04-07	1989-12-19	University Of Florida	Amino acids containing dihydropyridine ring systems for site-specific delivery of peptides to the brain
DE3879024T2 (de) *	1987-07-31	1993-10-07	Takeda Chemical Industries Ltd	Pyridinium-Derivate, ihre Herstellung und Verwendung.
DE4107570A1 (de) *	1991-03-07	1992-11-19	Diagnostikforschung Inst	Chelate, deren metallkomplexe sowie ihre verwendung in diagnostik und therapie
JP4677863B2 (ja) *	2005-09-05	2011-04-27	堺化学工業株式会社	チオール系光硬化性モノマーおよび光硬化型樹脂組成物
US8701166B2 (en)	2011-12-09	2014-04-15	Blackberry Limited	Secure authentication
US10864279B2 (en)	2016-12-16	2020-12-15	Industrial Technology Research Institute	Linker-drug and antibody-drug conjugate (ADC) employing the same

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3382795T2 (de) *	1982-05-18	1996-02-15	University Of Florida, Gainesville, Fla.	Gehirnspezifische arzneimittelabgabe.

1985
- 1985-07-15 AU AU46358/85A patent/AU4635885A/en not_active Abandoned
- 1985-07-15 EP EP85903633A patent/EP0187832A1/en not_active Withdrawn
- 1985-07-15 FI FI861118A patent/FI861118A0/fi not_active Application Discontinuation
- 1985-07-15 WO PCT/US1985/001334 patent/WO1986000898A1/en not_active Ceased
- 1985-07-18 GR GR851792A patent/GR851792B/el unknown
- 1985-07-18 KR KR1019850005137A patent/KR900007514B1/ko not_active Expired
- 1985-07-19 CA CA000487165A patent/CA1267899A/en not_active Expired - Lifetime
- 1985-07-19 ZA ZA855476A patent/ZA855476B/xx unknown
- 1985-07-19 JP JP60160040A patent/JPS61106556A/ja active Pending
- 1985-07-19 PT PT80841A patent/PT80841B/pt unknown
1986
- 1986-02-17 ES ES552072A patent/ES8704900A1/es not_active Expired
- 1986-03-14 NO NO860981A patent/NO860981L/no unknown
- 1986-03-18 DK DK124786A patent/DK124786A/da not_active Application Discontinuation

Also Published As

Publication number	Publication date
ES8704900A1 (es)	1987-04-16
ES552072A0 (es)	1987-04-16
GR851792B (mo)	1985-11-26
KR860000871A (ko)	1986-02-20
JPS61106556A (ja)	1986-05-24
FI861118L (fi)	1986-03-18
PT80841A (en)	1985-08-01
CA1267899A (en)	1990-04-17
AU4635885A (en)	1986-02-25
EP0187832A1 (en)	1986-07-23
DK124786D0 (da)	1986-03-18
ZA855476B (en)	1987-03-25
DK124786A (da)	1986-05-20
FI861118A7 (fi)	1986-03-18
FI861118A0 (fi)	1986-03-18
KR900007514B1 (ko)	1990-10-11
PT80841B (en)	1987-06-03
WO1986000898A1 (en)	1986-02-13

Publication	Publication Date	Title
US4963688A (en)	1990-10-16	Compounds for site-enhanced delivery of radionuclides and uses thereof
US6426346B1 (en)	2002-07-30	6-membered aromatics as factor Xa inhibitors
EP0329737A1 (en)	1989-08-30	Tri-aza macrocycles and metal complexes thereof
KR102842676B1 (ko)	2025-08-04	Khk 억제 효과를 갖는 화합물
JPH0764815B2 (ja)	1995-07-12	医薬用組成物に用いる化合物
SE445352B (sv)	1986-06-16	Forfarande for framstellning av dipeptider, vilka inhiberar overforing av angiotensin i till angiotensin ii
US20080139461A1 (en)	2008-06-12	Peptidomimetic Compounds and Preparation of Biologically Active Derivatives
US5679778A (en)	1997-10-21	Molecule labelling using 2-hydraninopyridine derivatives
US4963682A (en)	1990-10-16	Novel radiopharmaceuticals and chelating agents useful in their preparation
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