JP2003512379A - 性腺刺激ホルモン放出ホルモンレセプターアンタゴニストおよびそれに関連する方法 - Google Patents
性腺刺激ホルモン放出ホルモンレセプターアンタゴニストおよびそれに関連する方法Info
- Publication number
- JP2003512379A JP2003512379A JP2001531842A JP2001531842A JP2003512379A JP 2003512379 A JP2003512379 A JP 2003512379A JP 2001531842 A JP2001531842 A JP 2001531842A JP 2001531842 A JP2001531842 A JP 2001531842A JP 2003512379 A JP2003512379 A JP 2003512379A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- substituted
- alkyl
- fluorobenzyl
- compound
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 34
- 229940127445 Gonadotropin Releasing Hormone Receptor Antagonists Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims abstract description 25
- 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 claims abstract description 24
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims abstract description 23
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 claims abstract description 23
- 229940002612 prodrug Drugs 0.000 claims abstract description 11
- 239000000651 prodrug Substances 0.000 claims abstract description 11
- 239000003163 gonadal steroid hormone Substances 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000003937 drug carrier Substances 0.000 claims abstract description 5
- -1 2-pyridylethyl Chemical group 0.000 claims description 88
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 57
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 48
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 33
- 125000001072 heteroaryl group Chemical group 0.000 claims description 32
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 17
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000003107 substituted aryl group Chemical group 0.000 claims description 13
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 201000010260 leiomyoma Diseases 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 230000001817 pituitary effect Effects 0.000 claims description 9
- 206010046798 Uterine leiomyoma Diseases 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 7
- 201000009273 Endometriosis Diseases 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 102000006771 Gonadotropins Human genes 0.000 claims description 4
- 108010086677 Gonadotropins Proteins 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 239000002622 gonadotropin Substances 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 208000006155 precocious puberty Diseases 0.000 claims description 4
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 claims description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
- 206010020112 Hirsutism Diseases 0.000 claims description 3
- 206010036049 Polycystic ovaries Diseases 0.000 claims description 3
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
- 208000020221 Short stature Diseases 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 3
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 230000003042 antagnostic effect Effects 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 230000035935 pregnancy Effects 0.000 claims 2
- 208000003200 Adenoma Diseases 0.000 claims 1
- 206010001233 Adenoma benign Diseases 0.000 claims 1
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 206010025135 lupus erythematosus Diseases 0.000 claims 1
- 208000019116 sleep disease Diseases 0.000 claims 1
- 208000020685 sleep-wake disease Diseases 0.000 claims 1
- 206010046766 uterine cancer Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 46
- 239000002464 receptor antagonist Substances 0.000 abstract description 36
- 229940044551 receptor antagonist Drugs 0.000 abstract description 36
- 102000008238 LHRH Receptors Human genes 0.000 abstract description 33
- 108010021290 LHRH Receptors Proteins 0.000 abstract description 33
- 238000011282 treatment Methods 0.000 abstract description 16
- 238000009472 formulation Methods 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 87
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000002904 solvent Substances 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 37
- 239000000126 substance Substances 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 239000002585 base Substances 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 15
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000012442 inert solvent Substances 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 102000009151 Luteinizing Hormone Human genes 0.000 description 11
- 108010073521 Luteinizing Hormone Proteins 0.000 description 11
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- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 150000001299 aldehydes Chemical class 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 230000029936 alkylation Effects 0.000 description 9
- 238000005804 alkylation reaction Methods 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 description 7
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- 150000003335 secondary amines Chemical class 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000001350 alkyl halides Chemical class 0.000 description 6
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
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- 150000003141 primary amines Chemical class 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 5
- FFWQLZFIMNTUCZ-UHFFFAOYSA-N 1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CBr FFWQLZFIMNTUCZ-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
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- 239000000556 agonist Substances 0.000 description 4
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- 150000001721 carbon Chemical group 0.000 description 4
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- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000002710 gonadal effect Effects 0.000 description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
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- 125000004076 pyridyl group Chemical group 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 229910052717 sulfur Chemical group 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 description 3
- UEOCICLWNYTZBO-UHFFFAOYSA-N (3-methoxyphenoxy)boronic acid Chemical compound COC1=CC=CC(OB(O)O)=C1 UEOCICLWNYTZBO-UHFFFAOYSA-N 0.000 description 2
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- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical class C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P5/04—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin for decreasing, blocking or antagonising the activity of the hypothalamic hormones
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41876899A | 1999-10-15 | 1999-10-15 | |
| US09/418,768 | 1999-10-15 | ||
| PCT/US2000/028677 WO2001029044A1 (en) | 1999-10-15 | 2000-10-16 | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003512379A true JP2003512379A (ja) | 2003-04-02 |
| JP2003512379A5 JP2003512379A5 (https=) | 2007-11-22 |
Family
ID=23659500
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001531842A Pending JP2003512379A (ja) | 1999-10-15 | 2000-10-16 | 性腺刺激ホルモン放出ホルモンレセプターアンタゴニストおよびそれに関連する方法 |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1220857B1 (https=) |
| JP (1) | JP2003512379A (https=) |
| KR (1) | KR20020045609A (https=) |
| AT (1) | ATE305008T1 (https=) |
| AU (1) | AU769855B2 (https=) |
| CA (1) | CA2386942A1 (https=) |
| DE (1) | DE60022769T2 (https=) |
| ES (1) | ES2249302T3 (https=) |
| HK (1) | HK1047437B (https=) |
| MX (1) | MXPA02003614A (https=) |
| WO (1) | WO2001029044A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011506474A (ja) * | 2007-12-13 | 2011-03-03 | バーテックス ファーマシューティカルズ インコーポレイテッド | 嚢胞性線維症膜コンダクタンスレギュレーターのモジュレーター |
| WO2014133112A1 (ja) * | 2013-03-01 | 2014-09-04 | 国立大学法人東京大学 | オートタキシン阻害活性を有する８－置換イミダゾピリミジノン誘導体 |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001055119A2 (en) | 2000-01-25 | 2001-08-02 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| SK14512003A3 (sk) | 2001-04-30 | 2004-08-03 | Zentaris Gmbh | Spôsob liečenia demencie a neurodegeneratívnych chorôb strednými dávkami LHRH antagonistov |
| AU2002324586B2 (en) | 2001-08-02 | 2008-04-24 | Neurocrine Biosciences, Inc. | 1,3,5-triazine-2,4,6-triones, preparation and use as gonadotropin-releasing hormone receptor antagonists |
| EP1411941A2 (en) | 2001-08-02 | 2004-04-28 | Neurocrine Biosciences, Inc. | Pyridinone and pyridazinone derivatives as gonadotropin-releasing hormone receptor antagonists |
| WO2003011870A1 (en) * | 2001-08-02 | 2003-02-13 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists |
| JP2005500352A (ja) | 2001-08-02 | 2005-01-06 | ニューロクライン バイオサイエンシーズ， インコーポレイテッド | ゴナドトロピン放出ホルモンレセプター（ＧｎＲＨ）アンタゴニストとしての１，２，４−トリアジン−３，５−ジオン |
| US6939883B2 (en) | 2001-08-02 | 2005-09-06 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| WO2003068769A1 (en) | 2002-02-12 | 2003-08-21 | Pfizer Inc. | Non-peptide compounds affecting the action of gonadotropin-releasing hormone (gnrh) |
| CA2489252A1 (en) | 2002-06-13 | 2003-12-24 | Pfizer Inc. | Non-peptide gnrh agents, pharmaceutical compositions and methods for their use |
| ES2387495T3 (es) | 2003-07-07 | 2012-09-25 | Neurocrine Biosciences, Inc. | Arilpirimidinas útiles en el tratamiento de trastornos relacionados con las hormonas sexuales, tales como endometriosis, cáncer de próstata y similares |
| DE602004020638D1 (de) | 2003-07-07 | 2009-05-28 | Neurocrine Biosciences Inc | Pyrimidin-2,4-dion-derivate als gonadotropin freisetzende hormon-rezeptor-antagonisten |
| AU2004257639B2 (en) | 2003-07-07 | 2011-01-06 | Neurocrine Biosciences, Inc. | Pyrimidine-2, 4-dione derivatives as gonadotropin-releasing hormone receptor antagonists |
| CL2008000986A1 (es) | 2007-04-06 | 2008-10-17 | Neurocrine Biosciences Inc | COMPUESTO DERIVADO DE HETEROCICLOS DE NITROGENO, AGONISTAS DEL RECEPTOR GnRH; COMPOSICION FARMACEUTICA QUE COMPRENDE A DICHO COMPUESTO; Y USO PARA TRATAR UNA AFECCION RELACIONADA CON LAS HORMONAS SEXUALES, ENDOMETRIOSIS, DISMENORREA, ENFERMEDAD DE OV |
| EP2155194B1 (en) | 2007-04-06 | 2015-01-21 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| CN101987865B (zh) * | 2009-07-29 | 2014-07-30 | 中国人民解放军军事医学科学院毒物药物研究所 | 含有乙内酰脲结构的促黄体生成素释放激素拮抗剂 |
| TW201130854A (en) | 2009-12-22 | 2011-09-16 | Bayer Schering Pharma Ag | Pyridinone derivatives and pharmaceutical compositions thereof |
| WO2012175514A1 (en) | 2011-06-21 | 2012-12-27 | Bayer Intellectual Property Gmbh | Pyridinone derivatives and pharmaceutical compositions thereof |
| MX357841B (es) * | 2012-02-28 | 2018-07-26 | Tiumbio Co Ltd | Antagonistas de los receptores de la hormona liberadora de gonadotropina, método para la preparación de éstos y composición farmacéutica que los contienen. |
| KR101973074B1 (ko) | 2018-11-30 | 2019-04-26 | 주식회사 티움바이오 | 퓨로피리미딘 화합물의 염 및 결정형, 및 이를 포함하는 약학적 조성물 |
| CN114728167B (zh) | 2019-11-25 | 2024-03-19 | 安进公司 | 作为δ-5脱饱和酶抑制剂的杂环化合物以及使用方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999033831A1 (en) * | 1997-12-26 | 1999-07-08 | Takeda Chemical Industries, Ltd. | Nitrogen-containing heterocyclic compounds, their production and use |
| WO1999051232A1 (en) * | 1998-04-02 | 1999-10-14 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6081508A (en) * | 1998-02-25 | 2000-06-27 | Indus River Networks, Inc. | Remote computer communication |
-
2000
- 2000-10-16 MX MXPA02003614A patent/MXPA02003614A/es active IP Right Grant
- 2000-10-16 ES ES00973591T patent/ES2249302T3/es not_active Expired - Lifetime
- 2000-10-16 CA CA002386942A patent/CA2386942A1/en not_active Abandoned
- 2000-10-16 HK HK02109095.3A patent/HK1047437B/en not_active IP Right Cessation
- 2000-10-16 AT AT00973591T patent/ATE305008T1/de not_active IP Right Cessation
- 2000-10-16 DE DE60022769T patent/DE60022769T2/de not_active Expired - Fee Related
- 2000-10-16 AU AU12089/01A patent/AU769855B2/en not_active Ceased
- 2000-10-16 JP JP2001531842A patent/JP2003512379A/ja active Pending
- 2000-10-16 KR KR1020027004773A patent/KR20020045609A/ko not_active Withdrawn
- 2000-10-16 EP EP00973591A patent/EP1220857B1/en not_active Expired - Lifetime
- 2000-10-16 WO PCT/US2000/028677 patent/WO2001029044A1/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999033831A1 (en) * | 1997-12-26 | 1999-07-08 | Takeda Chemical Industries, Ltd. | Nitrogen-containing heterocyclic compounds, their production and use |
| WO1999051232A1 (en) * | 1998-04-02 | 1999-10-14 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011506474A (ja) * | 2007-12-13 | 2011-03-03 | バーテックス ファーマシューティカルズ インコーポレイテッド | 嚢胞性線維症膜コンダクタンスレギュレーターのモジュレーター |
| WO2014133112A1 (ja) * | 2013-03-01 | 2014-09-04 | 国立大学法人東京大学 | オートタキシン阻害活性を有する８－置換イミダゾピリミジノン誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2386942A1 (en) | 2001-04-26 |
| MXPA02003614A (es) | 2002-10-23 |
| ES2249302T3 (es) | 2006-04-01 |
| AU1208901A (en) | 2001-04-30 |
| EP1220857A1 (en) | 2002-07-10 |
| DE60022769D1 (de) | 2006-02-02 |
| HK1047437A1 (en) | 2003-02-21 |
| DE60022769T2 (de) | 2006-07-06 |
| KR20020045609A (ko) | 2002-06-19 |
| EP1220857B1 (en) | 2005-09-21 |
| AU769855B2 (en) | 2004-02-05 |
| ATE305008T1 (de) | 2005-10-15 |
| WO2001029044A1 (en) | 2001-04-26 |
| HK1047437B (en) | 2005-12-16 |
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