HUP0303219A2 - Kinolin-, izokinolin- és ftalazinszármazékok mint gonadotropinfelszabadító hormon antagonisták és eljárás az előállításukra - Google Patents

Kinolin-, izokinolin- és ftalazinszármazékok mint gonadotropinfelszabadító hormon antagonisták és eljárás az előállításukra Download PDF

Info

Publication number: HUP0303219A2
Authority: HU; Hungary
Prior art keywords: group; general formula; optionally substituted; alkyl; atom
Prior art date: 2001-02-21

Application number

HU0303219A

Other languages

English (en)

Hungarian (hu)

Inventor

Ulrich Bühmann

Peter Dröscher

Eckhard Günther

Holger Hess-Stumpp

Roland Kühne

Peter Muhn

Emmanuel Polymeropoulos

Norbert Schmees

Peter Strehlke

Antonius Marinus Ter Laak

Original Assignee

Zentaris Gmbh.

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

2001-02-21

Filing date

2002-02-21

Publication date

2003-12-29

2001-02-21 Priority claimed from DE2001108271 external-priority patent/DE10108271A1/de

2002-02-21 Application filed by Zentaris Gmbh. filed Critical Zentaris Gmbh.

2003-12-29 Publication of HUP0303219A2 publication Critical patent/HUP0303219A2/hu

Links

239000000579 Gonadotropin-Releasing Hormone Substances 0.000 title claims abstract description 15
101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 title claims abstract description 15
XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 title claims abstract description 15
229940035638 gonadotropin-releasing hormone Drugs 0.000 title claims abstract description 15
239000005557 antagonist Substances 0.000 title claims description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 title description 4
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical class C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 87
-1 Z means direct bond Chemical compound 0.000 claims abstract description 60
125000000217 alkyl group Chemical group 0.000 claims abstract description 50
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 30
125000005843 halogen group Chemical group 0.000 claims abstract description 25
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 9
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 7
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 6
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
239000001301 oxygen Substances 0.000 claims abstract description 6
229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 5
150000003839 salts Chemical class 0.000 claims abstract description 5
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
239000002253 acid Substances 0.000 claims abstract description 3
125000002947 alkylene group Chemical group 0.000 claims abstract description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 3
239000011593 sulfur Substances 0.000 claims abstract 3
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims abstract 2
125000002252 acyl group Chemical group 0.000 claims abstract 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
229910052751 metal Chemical group 0.000 claims description 13
239000002184 metal Chemical group 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 11
125000003118 aryl group Chemical group 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 9
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
230000035558 fertility Effects 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
125000001624 naphthyl group Chemical group 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
239000003054 catalyst Substances 0.000 claims description 4
125000004122 cyclic group Chemical group 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
238000000034 method Methods 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
229910052755 nonmetal Inorganic materials 0.000 claims description 4
125000000962 organic group Chemical group 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
206010028980 Neoplasm Diseases 0.000 claims description 3
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
238000001794 hormone therapy Methods 0.000 claims description 3
208000000509 infertility Diseases 0.000 claims description 3
230000036512 infertility Effects 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 3
150000007513 acids Chemical class 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
231100000535 infertility Toxicity 0.000 claims description 2
230000005764 inhibitory process Effects 0.000 claims description 2
125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
150000001721 carbon Chemical group 0.000 claims 1
229910052740 iodine Inorganic materials 0.000 claims 1
238000004519 manufacturing process Methods 0.000 abstract description 5
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract description 3
125000004434 sulfur atom Chemical group 0.000 abstract description 3
230000003042 antagnostic effect Effects 0.000 abstract description 2
CKFGINPQOCXMAZ-UHFFFAOYSA-N methanediol Chemical compound OCO CKFGINPQOCXMAZ-UHFFFAOYSA-N 0.000 abstract 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 description 15
239000000243 solution Substances 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
239000000203 mixture Substances 0.000 description 10
210000004027 cell Anatomy 0.000 description 8
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
239000006260 foam Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
239000003480 eluent Substances 0.000 description 6
229940088597 hormone Drugs 0.000 description 6
239000005556 hormone Substances 0.000 description 6
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 6
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
238000012360 testing method Methods 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000011575 calcium Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
230000002483 superagonistic effect Effects 0.000 description 5
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
239000003098 androgen Substances 0.000 description 4
229910052788 barium Inorganic materials 0.000 description 4
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 4
229910052792 caesium Inorganic materials 0.000 description 4
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 4
229910052791 calcium Inorganic materials 0.000 description 4
201000010099 disease Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
230000000694 effects Effects 0.000 description 4
229940011871 estrogen Drugs 0.000 description 4
239000000262 estrogen Substances 0.000 description 4
229910052744 lithium Inorganic materials 0.000 description 4
239000011591 potassium Substances 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 3
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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108010037003 Buserelin Proteins 0.000 description 3
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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
102000008238 LHRH Receptors Human genes 0.000 description 3
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KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
206010046798 Uterine leiomyoma Diseases 0.000 description 3
CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 3
229960002719 buserelin Drugs 0.000 description 3
229910052802 copper Inorganic materials 0.000 description 3
239000010949 copper Substances 0.000 description 3
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
RTAHXZKDHJCUQD-UHFFFAOYSA-N ethyl 6-(4-acetamidophenoxy)-5-(chloromethyl)-1-[(2,6-difluorophenyl)methyl]-4-oxoquinoline-3-carboxylate Chemical compound C12=CC=C(OC=3C=CC(NC(C)=O)=CC=3)C(CCl)=C2C(=O)C(C(=O)OCC)=CN1CC1=C(F)C=CC=C1F RTAHXZKDHJCUQD-UHFFFAOYSA-N 0.000 description 3
239000003163 gonadal steroid hormone Substances 0.000 description 3
239000002474 gonadorelin antagonist Substances 0.000 description 3
229910052736 halogen Inorganic materials 0.000 description 3
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
201000010260 leiomyoma Diseases 0.000 description 3
239000000463 material Substances 0.000 description 3
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
239000008188 pellet Substances 0.000 description 3
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239000002244 precipitate Substances 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
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238000010792 warming Methods 0.000 description 3
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125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
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125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
229960004622 raloxifene Drugs 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
239000000523 sample Substances 0.000 description 1
238000007790 scraping Methods 0.000 description 1
208000008742 seborrheic dermatitis Diseases 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
230000021595 spermatogenesis Effects 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
238000010257 thawing Methods 0.000 description 1
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
201000007954 uterine fibroid Diseases 0.000 description 1
238000003466 welding Methods 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Endocrinology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Reproductive Health (AREA)
Diabetes (AREA)
Gynecology & Obstetrics (AREA)
Epidemiology (AREA)
Pregnancy & Childbirth (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Quinoline Compounds (AREA)

HU0303219A 2001-02-21 2002-02-21 Kinolin-, izokinolin- és ftalazinszármazékok mint gonadotropinfelszabadító hormon antagonisták és eljárás az előállításukra HUP0303219A2 (hu)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE2001108271 DE10108271A1 (de)	2001-02-21	2001-02-21	Chinolin-, Isochinolin- und Phthalazinderivate als Antagonisten des Gonadotropin freisetzenden Hormons
US27491401P	2001-03-13	2001-03-13
PCT/EP2002/001882 WO2002066437A1 (de)	2001-02-21	2002-02-21	Chinolin-, isochinolin- und phthalazinderivate als antagonisten des gonadotropin freisetzenden hormons

Publications (1)

Publication Number	Publication Date
HUP0303219A2 true HUP0303219A2 (hu)	2003-12-29

Family

ID=26008581

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HU0303219A HUP0303219A2 (hu)	2001-02-21	2002-02-21	Kinolin-, izokinolin- és ftalazinszármazékok mint gonadotropinfelszabadító hormon antagonisták és eljárás az előállításukra

Country Status (17)

Country	Link
EP (1)	EP1362034A1 (no)
JP (1)	JP2004528298A (no)
CN (1)	CN1496354A (no)
AU (1)	AU2002247737B2 (no)
BG (1)	BG108165A (no)
BR (1)	BR0207451A (no)
CA (1)	CA2438709A1 (no)
CZ (1)	CZ20032514A3 (no)
HU (1)	HUP0303219A2 (no)
IL (1)	IL157303A0 (no)
MX (1)	MXPA03007348A (no)
NO (1)	NO325675B1 (no)
NZ (1)	NZ527597A (no)
PL (1)	PL367285A1 (no)
RU (1)	RU2280031C2 (no)
SK (1)	SK11622003A3 (no)
WO (1)	WO2002066437A1 (no)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2968323A4 (en)	2013-03-13	2016-12-14	Flatley Discovery Lab	PYRIDAZINONE COMPOUNDS AND METHODS FOR THE TREATMENT OF CYSTIC FIBROSIS

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4120646A1 (de) *	1991-06-22	1992-12-24	Bayer Ag	7-isoindolinyl-chinolon- und naphthyridoncarbonsaeure-derivate
CN1200114A (zh) *	1995-10-19	1998-11-25	武田药品工业株式会社	作为gnrh拮抗剂的喹啉衍生物
WO1997044041A1 (en) *	1996-05-20	1997-11-27	Merck & Co., Inc.	Antagonists of gonadotropin releasing hormone

2002
- 2002-02-21 JP JP2002565954A patent/JP2004528298A/ja active Pending
- 2002-02-21 IL IL15730302A patent/IL157303A0/xx unknown
- 2002-02-21 MX MXPA03007348A patent/MXPA03007348A/es active IP Right Grant
- 2002-02-21 CA CA002438709A patent/CA2438709A1/en not_active Abandoned
- 2002-02-21 SK SK1162-2003A patent/SK11622003A3/sk unknown
- 2002-02-21 EP EP02716803A patent/EP1362034A1/de not_active Withdrawn
- 2002-02-21 HU HU0303219A patent/HUP0303219A2/hu unknown
- 2002-02-21 CZ CZ20032514A patent/CZ20032514A3/cs unknown
- 2002-02-21 NZ NZ527597A patent/NZ527597A/en unknown
- 2002-02-21 WO PCT/EP2002/001882 patent/WO2002066437A1/de not_active Ceased
- 2002-02-21 RU RU2003128647/04A patent/RU2280031C2/ru not_active IP Right Cessation
- 2002-02-21 AU AU2002247737A patent/AU2002247737B2/en not_active Ceased
- 2002-02-21 BR BR0207451-6A patent/BR0207451A/pt not_active IP Right Cessation
- 2002-02-21 CN CNA028063597A patent/CN1496354A/zh active Pending
- 2002-02-21 PL PL02367285A patent/PL367285A1/xx not_active Application Discontinuation
2003
- 2003-08-20 NO NO20033698A patent/NO325675B1/no not_active IP Right Cessation
- 2003-09-09 BG BG108165A patent/BG108165A/xx unknown

Also Published As

Publication number	Publication date
MXPA03007348A (es)	2003-12-04
AU2002247737B2 (en)	2006-05-18
CZ20032514A3 (cs)	2004-05-12
CA2438709A1 (en)	2002-08-29
SK11622003A3 (sk)	2004-01-08
NO325675B1 (no)	2008-07-07
NO20033698L (no)	2003-10-20
CN1496354A (zh)	2004-05-12
BR0207451A (pt)	2004-06-01
PL367285A1 (en)	2005-02-21
RU2280031C2 (ru)	2006-07-20
NZ527597A (en)	2004-10-29
IL157303A0 (en)	2004-02-19
BG108165A (en)	2004-08-31
JP2004528298A (ja)	2004-09-16
EP1362034A1 (de)	2003-11-19
NO20033698D0 (no)	2003-08-20
RU2003128647A (ru)	2005-03-27
WO2002066437A1 (de)	2002-08-29

Legal Events

Date

Code

Title

Description

2006-08-28

HC9A

Change of name, address

Owner name: ZENTARIS GMBH., DE

Free format text: FORMER OWNER(S): ZENTARIS GMBH., DE

2010-10-28

FD9A

Lapse of provisional protection due to non-payment of fees

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