CA2112566A1 - Analogues non desensibilisants de la gnrh et d'autres ligands biologiquement actifs - Google Patents

Analogues non desensibilisants de la gnrh et d'autres ligands biologiquement actifs

Info

Publication number: CA2112566A1
Authority: CA; Canada
Prior art keywords: alkyl; formula; analog; phe; gnrh
Prior art date: 1991-07-01
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.): Abandoned

Application number

CA 2112566

Other languages

English (en)

Inventor

Graham J. Moore

Hamid R. Habibi

John M. Matsoukas

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

University Technologies International Inc

Original Assignee

Individual

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.)

1991-07-01

Filing date

1992-07-02

Publication date

1993-02-18

1992-07-02 Application filed by Individual filed Critical Individual

1993-02-18 Publication of CA2112566A1 publication Critical patent/CA2112566A1/fr

Status Abandoned legal-status Critical Current

Links

239000003446 ligand Substances 0.000 title claims abstract description 146
101150108262 gnrh1 gene Proteins 0.000 title 1
101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims abstract description 124
NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 claims abstract description 116
238000000034 method Methods 0.000 claims abstract description 85
150000001875 compounds Chemical class 0.000 claims abstract description 59
239000000203 mixture Substances 0.000 claims abstract description 20
239000003399 opiate peptide Substances 0.000 claims abstract description 18
108010093625 Opioid Peptides Proteins 0.000 claims abstract description 17
102000001490 Opioid Peptides Human genes 0.000 claims abstract description 17
-1 2,4-dichlorobenzyl Chemical group 0.000 claims description 85
125000000217 alkyl group Chemical group 0.000 claims description 80
125000003118 aryl group Chemical group 0.000 claims description 61
229910052757 nitrogen Inorganic materials 0.000 claims description 57
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 51
239000002253 acid Substances 0.000 claims description 50
229910052717 sulfur Inorganic materials 0.000 claims description 47
125000004432 carbon atom Chemical group C* 0.000 claims description 45
108090000765 processed proteins & peptides Proteins 0.000 claims description 39
229910052799 carbon Inorganic materials 0.000 claims description 33
125000000753 cycloalkyl group Chemical group 0.000 claims description 33
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 33
125000004433 nitrogen atom Chemical group N* 0.000 claims description 33
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 32
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 description 32
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 28
125000001841 imino group Chemical group [H]N=* 0.000 claims description 27
229910052760 oxygen Inorganic materials 0.000 claims description 26
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims description 25
125000006239 protecting group Chemical group 0.000 claims description 24
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 24
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical group NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 23
125000003342 alkenyl group Chemical group 0.000 claims description 20
150000001413 amino acids Chemical class 0.000 claims description 20
125000004430 oxygen atom Chemical group O* 0.000 claims description 20
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 20
239000011347 resin Substances 0.000 claims description 20
229920005989 resin Polymers 0.000 claims description 20
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 19
150000004820 halides Chemical class 0.000 claims description 19
229910052698 phosphorus Inorganic materials 0.000 claims description 19
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
125000004434 sulfur atom Chemical group 0.000 claims description 17
230000003993 interaction Effects 0.000 claims description 16
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 16
125000002252 acyl group Chemical group 0.000 claims description 15
239000005557 antagonist Substances 0.000 claims description 15
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 14
125000001188 haloalkyl group Chemical group 0.000 claims description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 13
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 claims description 12
OUYCCCASQSFEME-MRVPVSSYSA-N D-tyrosine Chemical compound OC(=O)[C@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-MRVPVSSYSA-N 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 claims description 10
229930195721 D-histidine Natural products 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
229910018830 PO3H Inorganic materials 0.000 claims description 10
125000000304 alkynyl group Chemical group 0.000 claims description 10
150000003536 tetrazoles Chemical class 0.000 claims description 10
150000008574 D-amino acids Chemical group 0.000 claims description 9
229930195709 D-tyrosine Natural products 0.000 claims description 9
229910006074 SO2NH2 Inorganic materials 0.000 claims description 9
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
XJODGRWDFZVTKW-LURJTMIESA-N (2s)-4-methyl-2-(methylamino)pentanoic acid Chemical compound CN[C@H](C(O)=O)CC(C)C XJODGRWDFZVTKW-LURJTMIESA-N 0.000 claims description 7
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 7
125000003047 N-acetyl group Chemical group 0.000 claims description 7
229910006069 SO3H Inorganic materials 0.000 claims description 7
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 7
125000001931 aliphatic group Chemical group 0.000 claims description 7
150000003973 alkyl amines Chemical class 0.000 claims description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 7
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 7
125000003709 fluoroalkyl group Chemical group 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
125000005561 phenanthryl group Chemical group 0.000 claims description 7
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 6
229960003604 testosterone Drugs 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 claims description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 4
150000003431 steroids Chemical class 0.000 claims description 4
OMGHIGVFLOPEHJ-UHFFFAOYSA-N 2,5-dihydro-1h-pyrrol-1-ium-2-carboxylate Chemical compound OC(=O)C1NCC=C1 OMGHIGVFLOPEHJ-UHFFFAOYSA-N 0.000 claims description 3
241000972773 Aulopiformes Species 0.000 claims description 3
FGXWKSZFVQUSTL-UHFFFAOYSA-N domperidone Chemical compound C12=CC=CC=C2NC(=O)N1CCCN(CC1)CCC1N1C2=CC=C(Cl)C=C2NC1=O FGXWKSZFVQUSTL-UHFFFAOYSA-N 0.000 claims description 3
229960001253 domperidone Drugs 0.000 claims description 3
235000019515 salmon Nutrition 0.000 claims description 3
230000002194 synthesizing effect Effects 0.000 claims description 3
DCXYFEDJOCDNAF-UWTATZPHSA-N D-Asparagine Chemical compound OC(=O)[C@H](N)CC(N)=O DCXYFEDJOCDNAF-UWTATZPHSA-N 0.000 claims description 2
CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 2
AHLPHDHHMVZTML-SCSAIBSYSA-N D-Ornithine Chemical compound NCCC[C@@H](N)C(O)=O AHLPHDHHMVZTML-SCSAIBSYSA-N 0.000 claims description 2
MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 2
ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 claims description 2
CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 2
QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims description 2
125000000539 amino acid group Chemical group 0.000 claims description 2
229940035638 gonadotropin-releasing hormone Drugs 0.000 claims 23
241001367053 Autographa gamma Species 0.000 claims 7
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims 7
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 5
229940127240 opiate Drugs 0.000 claims 4
125000000570 L-alpha-aspartyl group Chemical group [H]OC(=O)C([H])([H])[C@]([H])(N([H])[H])C(*)=O 0.000 claims 3
125000000010 L-asparaginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(=O)N([H])[H] 0.000 claims 3
125000000635 L-ornithyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 claims 3
125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 claims 3
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 3
241000287828 Gallus gallus Species 0.000 claims 2
238000005481 NMR spectroscopy Methods 0.000 claims 2
150000003943 catecholamines Chemical class 0.000 claims 2
238000001506 fluorescence spectroscopy Methods 0.000 claims 2
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 2
241000352333 Amegilla alpha Species 0.000 claims 1
XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 claims 1
125000002437 D-histidyl group Chemical group N[C@@H](C(=O)*)CC=1N=CNC1 0.000 claims 1
238000003776 cleavage reaction Methods 0.000 claims 1
230000007017 scission Effects 0.000 claims 1
102000005962 receptors Human genes 0.000 description 61
108020003175 receptors Proteins 0.000 description 61
229940024606 amino acid Drugs 0.000 description 32
235000001014 amino acid Nutrition 0.000 description 24
230000000694 effects Effects 0.000 description 18
239000004480 active ingredient Substances 0.000 description 15
239000000556 agonist Substances 0.000 description 14
238000000586 desensitisation Methods 0.000 description 14
102000004196 processed proteins & peptides Human genes 0.000 description 14
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
230000000295 complement effect Effects 0.000 description 11
238000009472 formulation Methods 0.000 description 11
230000001817 pituitary effect Effects 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 8
230000004048 modification Effects 0.000 description 8
238000012986 modification Methods 0.000 description 8
230000000541 pulsatile effect Effects 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
230000004071 biological effect Effects 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
230000001270 agonistic effect Effects 0.000 description 6
230000027455 binding Effects 0.000 description 6
230000001965 increasing effect Effects 0.000 description 6
239000007788 liquid Substances 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 6
229940031826 phenolate Drugs 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
238000012546 transfer Methods 0.000 description 6
102400000345 Angiotensin-2 Human genes 0.000 description 5
101800000733 Angiotensin-2 Proteins 0.000 description 5
241000252229 Carassius auratus Species 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
102000006771 Gonadotropins Human genes 0.000 description 5
108010086677 Gonadotropins Proteins 0.000 description 5
CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 5
241001024304 Mino Species 0.000 description 5
230000009471 action Effects 0.000 description 5
229950006323 angiotensin ii Drugs 0.000 description 5
239000012634 fragment Substances 0.000 description 5
239000002622 gonadotropin Substances 0.000 description 5
239000004615 ingredient Substances 0.000 description 5
239000000243 solution Substances 0.000 description 5
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
241001514645 Agonis Species 0.000 description 4
206010062767 Hypophysitis Diseases 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
125000003275 alpha amino acid group Chemical group 0.000 description 4
IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 4
230000008512 biological response Effects 0.000 description 4
150000001721 carbon Chemical group 0.000 description 4
239000000969 carrier Substances 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000012528 membrane Substances 0.000 description 4
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
230000008569 process Effects 0.000 description 4
239000007790 solid phase Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
102000008873 Angiotensin II receptor Human genes 0.000 description 3
108050000824 Angiotensin II receptor Proteins 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
241000700159 Rattus Species 0.000 description 3
230000004913 activation Effects 0.000 description 3
230000003042 antagnostic effect Effects 0.000 description 3
230000008901 benefit Effects 0.000 description 3
239000007822 coupling agent Substances 0.000 description 3
230000003247 decreasing effect Effects 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
229940094892 gonadotropins Drugs 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
238000007069 methylation reaction Methods 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000004044 response Effects 0.000 description 3
239000002904 solvent Substances 0.000 description 3
NMJREATYWWNIKX-XJIZABAQSA-N (2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[2-[[(2s)-1-[[(2s)-1-[(2s)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-(1h-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)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=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 NMJREATYWWNIKX-XJIZABAQSA-N 0.000 description 2
XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
101150034533 ATIC gene Proteins 0.000 description 2
241000220479 Acacia Species 0.000 description 2
QMMRCKSBBNJCMR-KMZPNFOHSA-N Angiotensin III Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCN=C(N)N)C(C)C)C1=CC=C(O)C=C1 QMMRCKSBBNJCMR-KMZPNFOHSA-N 0.000 description 2
102400000348 Angiotensin-3 Human genes 0.000 description 2
101800000738 Angiotensin-3 Proteins 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
101000996738 Gallus gallus Gonadoliberin-2 Proteins 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 2
125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 2
DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical compound OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
150000001447 alkali salts Chemical class 0.000 description 2
230000004075 alteration Effects 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
230000007423 decrease Effects 0.000 description 2
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
230000035558 fertility Effects 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
229960002591 hydroxyproline Drugs 0.000 description 2
238000002513 implantation Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
230000011987 methylation Effects 0.000 description 2
229960005181 morphine Drugs 0.000 description 2
230000016087 ovulation Effects 0.000 description 2
238000010647 peptide synthesis reaction Methods 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
239000000047 product Substances 0.000 description 2
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
238000011084 recovery Methods 0.000 description 2
239000007787 solid Substances 0.000 description 2
241000894007 species Species 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
YTBKOFZZSHCXGJ-QRPNPIFTSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;phenol Chemical compound OC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 YTBKOFZZSHCXGJ-QRPNPIFTSA-N 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
SLLUIGOIGZOBMZ-UHFFFAOYSA-N 2-[4-(1-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound CC(O)N1CCN(CCS(O)(=O)=O)CC1 SLLUIGOIGZOBMZ-UHFFFAOYSA-N 0.000 description 1
SJVGFKBLUYAEOK-SFHVURJKSA-N 6-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-4-carbonitrile Chemical compound FC=1C=C(C=C(C=1)F)[C@@H]1CC=NN1C(=O)C1CCN(CC1)C1=CC(=NC=N1)C#N SJVGFKBLUYAEOK-SFHVURJKSA-N 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
102000015427 Angiotensins Human genes 0.000 description 1
108010064733 Angiotensins Proteins 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
229910014033 C-OH Inorganic materials 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
101000904177 Clupea pallasii Gonadoliberin-1 Proteins 0.000 description 1
229910014570 C—OH Inorganic materials 0.000 description 1
ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 1
108010065372 Dynorphins Proteins 0.000 description 1
201000009273 Endometriosis Diseases 0.000 description 1
108010049140 Endorphins Proteins 0.000 description 1
102000009025 Endorphins Human genes 0.000 description 1
108700012941 GNRH1 Proteins 0.000 description 1
101500028367 Gallus gallus Gonadoliberin-1 Proteins 0.000 description 1
239000012981 Hank's balanced salt solution Substances 0.000 description 1
102000003710 Histamine H2 Receptors Human genes 0.000 description 1
108090000050 Histamine H2 Receptors Proteins 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
102000003746 Insulin Receptor Human genes 0.000 description 1
108010001127 Insulin Receptor Proteins 0.000 description 1
102000008238 LHRH Receptors Human genes 0.000 description 1
108010021290 LHRH Receptors Proteins 0.000 description 1
108010022337 Leucine Enkephalin Proteins 0.000 description 1
102000009151 Luteinizing Hormone Human genes 0.000 description 1
108010073521 Luteinizing Hormone Proteins 0.000 description 1
YFGBQHOOROIVKG-FKBYEOEOSA-N Met-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 YFGBQHOOROIVKG-FKBYEOEOSA-N 0.000 description 1
108010042237 Methionine Enkephalin Proteins 0.000 description 1
125000002405 N(2)-D-histidino group Chemical group C(=O)(O)[C@@H](CC=1N=CNC1)N* 0.000 description 1
206010033122 Ovarian atrophy Diseases 0.000 description 1
241001494479 Pecora Species 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
206010046764 Uterine atrophy Diseases 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
238000007098 aminolysis reaction Methods 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
239000011324 bead Substances 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
108091008324 binding proteins Proteins 0.000 description 1
102000023732 binding proteins Human genes 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
229960001380 cimetidine Drugs 0.000 description 1
229960004126 codeine Drugs 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
230000001010 compromised effect Effects 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000006071 cream Substances 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
PQZTVWVYCLIIJY-UHFFFAOYSA-N diethyl(propyl)amine Chemical compound CCCN(CC)CC PQZTVWVYCLIIJY-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
239000003210 dopamine receptor blocking agent Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
JMNJYGMAUMANNW-FIXZTSJVSA-N dynorphin a Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 JMNJYGMAUMANNW-FIXZTSJVSA-N 0.000 description 1
230000007515 enzymatic degradation Effects 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
230000012173 estrus Effects 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
230000000763 evoking effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
230000004720 fertilization Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
235000019688 fish Nutrition 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
229940028334 follicle stimulating hormone Drugs 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
210000002149 gonad Anatomy 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000003054 hormonal effect Effects 0.000 description 1
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
210000003016 hypothalamus Anatomy 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
230000009027 insemination Effects 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000000366 juvenile effect Effects 0.000 description 1
150000003951 lactams Chemical class 0.000 description 1
201000010260 leiomyoma Diseases 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
230000001050 lubricating effect Effects 0.000 description 1
229940040129 luteinizing hormone Drugs 0.000 description 1
101150019727 malQ gene Proteins 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
208000008013 morphine dependence Diseases 0.000 description 1
238000000465 moulding Methods 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
229960000988 nystatin Drugs 0.000 description 1
VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
231100001043 ovarian atrophy Toxicity 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
239000011148 porous material Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
244000144977 poultry Species 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
229960003712 propranolol Drugs 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000009877 rendering Methods 0.000 description 1
230000003252 repetitive effect Effects 0.000 description 1
230000001850 reproductive effect Effects 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
102220317710 rs1553881759 Human genes 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000012306 spectroscopic technique Methods 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000003270 steroid hormone Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
230000002483 superagonistic effect Effects 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
WZCZNEGTXVXAAS-UHFFFAOYSA-N trifluoromethanol Chemical compound OC(F)(F)F WZCZNEGTXVXAAS-UHFFFAOYSA-N 0.000 description 1
231100001042 uterine atrophy Toxicity 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1
NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical class [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/14—Angiotensins: Related peptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
- C07K1/042—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers characterised by the nature of the carrier
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/665—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/23—Luteinising hormone-releasing hormone [LHRH]; Related peptides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Gastroenterology & Hepatology (AREA)
Zoology (AREA)
Toxicology (AREA)
Analytical Chemistry (AREA)
Vascular Medicine (AREA)
Endocrinology (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA 2112566 1991-07-01 1992-07-02 Analogues non desensibilisants de la gnrh et d'autres ligands biologiquement actifs Abandoned CA2112566A1 (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US72132491A	1991-07-01	1991-07-01
US721,324		1991-07-01

Publications (1)

Publication Number	Publication Date
CA2112566A1 true CA2112566A1 (fr)	1993-02-18

Family

ID=24897506

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2112566 Abandoned CA2112566A1 (fr)	1991-07-01	1992-07-02	Analogues non desensibilisants de la gnrh et d'autres ligands biologiquement actifs

Country Status (4)

Country	Link
EP (1)	EP0592512A1 (fr)
JP (1)	JPH06509075A (fr)
CA (1)	CA2112566A1 (fr)
WO (1)	WO1993003058A2 (fr)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9100468D0 (en) *	1991-01-09	1991-02-20	Proteus Molecular Design	Improvements in and relating to hormones
US5688506A (en) *	1994-01-27	1997-11-18	Aphton Corp.	Immunogens against gonadotropin releasing hormone
US5677184A (en) *	1994-04-19	1997-10-14	Takeda Chemical Industries, Ltd.	CHO cells that express human LH-RH receptor
SI20424A (sl) *	1998-03-05	2001-06-30	Agouron Pharmaceuticals, Inc.	Nepeptidna GnRH sredstva
EA200100255A1 (ru)	1998-08-20	2002-02-28	Агурон Фармасьютикалз, Инк.	НЕПЕПТИДНЫЕ СРЕДСТВА GnRH, СПОСОБЫ И ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ ДЛЯ ИХ ПОЛУЧЕНИЯ
ATE394114T1 (de)	2001-03-08	2008-05-15	Univ Tulane	Somatostatin-antagonisten
AU2003202115A1 (en)	2002-02-12	2003-09-04	Pfizer Inc.	Non-peptide compounds affecting the action of gonadotropin-releasing hormone (gnrh)
US6861236B2 (en)	2002-05-24	2005-03-01	Applied Nanosystems B.V.	Export and modification of (poly)peptides in the lantibiotic way
AU2003233127A1 (en)	2002-06-13	2003-12-31	Pfizer Inc.	Non-peptide gnrh agents, pharmaceutical compositions and methods for their use
GB0307777D0 (en)	2003-04-04	2003-05-07	Medical Res Council	Conjugate compounds
RU2554087C2 (ru)	2009-12-18	2015-06-27	Айденикс Фармасьютикалз, Инк.	5,5-конденсированные ариленовые или гетероариленовые ингибиторы вируса гепатита с
EP2528934A4 (fr) *	2010-01-25	2013-08-21	Univ Cornell	Peptides aromatiques-cationiques et leurs utilisations

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3333752A1 (de) *	1983-09-19	1985-04-11	Victor Dipl.- Chem. 8000 München Brantl	Pharmakologisch aktive peptide
US5110904A (en) *	1989-08-07	1992-05-05	Abbott Laboratories	Lhrh analogs
EP0557276A1 (fr) *	1989-12-29	1993-09-01	University Technologies International Inc. (Uti)	Methodes de modelage des structures tertiaires de ligands biologiquement actifs, y compris leurs agonistes et antagonistes et nouveaux antagonistes synthetiques bases sur l'angiotensine

1992
- 1992-07-02 WO PCT/CA1992/000281 patent/WO1993003058A2/fr not_active Ceased
- 1992-07-02 JP JP5501722A patent/JPH06509075A/ja active Pending
- 1992-07-02 EP EP92914041A patent/EP0592512A1/fr not_active Withdrawn
- 1992-07-02 CA CA 2112566 patent/CA2112566A1/fr not_active Abandoned

Also Published As

Publication number	Publication date
JPH06509075A (ja)	1994-10-13
WO1993003058A2 (fr)	1993-02-18
EP0592512A1 (fr)	1994-04-20
WO1993003058A3 (fr)	1993-05-27

Publication	Publication Date	Title
US6423686B1 (en)	2002-07-23	LHRH antagonist peptides
US5140009A (en)	1992-08-18	Octapeptide LHRH antagonists
RU2199549C2 (ru)	2003-02-27	Антагонисты gnrh, модифицированные в положениях 5 и 6
JP4346115B2 (ja)	2009-10-21	Ｌｈ−ｒｈペプチド類似体、その使用及びそれを含有する薬用組成物
DE3850789T2 (de)	1995-03-09	Nonapeptid- und Dekapeptid-Analoge von LHRH, die als LHRH-Antagonisten dienen.
JPH05503689A (ja)	1993-06-17	ＧｎＲＨ類似体
CA2112566A1 (fr)	1993-02-18	Analogues non desensibilisants de la gnrh et d'autres ligands biologiquement actifs
JPH0689037B2 (ja)	1994-11-09	ＧｎＲＨ拮抗物質
KR900007864B1 (ko)	1990-10-22	GnRH 길항제 IX의 제조방법
JPH05503529A (ja)	1993-06-10	環状ＧｎＲＨアンタゴニスト
KR0123009B1 (ko)	1997-11-24	쥐이엔알에이취(GnRH) 유사체
CZ284168B6 (cs)	1998-09-16	Způsob navrhování a syntetizace antagonistů LHRH
US5480969A (en)	1996-01-02	Antagonists of LHRH
JP6100699B2 (ja)	2017-03-22	環状ｃｒｆアンタゴニストペプチド及びその薬学的に許容される塩
CA2293664A1 (fr)	1998-12-10	Peptides liberateurs de f.s.h.
US6300471B1 (en)	2001-10-09	FSH-releasing peptides
US6407205B1 (en)	2002-06-18	FSH-releasing peptides
Folkers et al.	1996	Antagonists of LHRH
US6455499B1 (en)	2002-09-24	Methods for treating disorders associated with LHRH activity
KR910002702B1 (ko)	1991-05-03	펩티드의 제법
MXPA99011169A (en)	2000-05-01	Lh-rh peptide analogues, their uses and pharmaceutical compositions containing them
AU3130100A (en)	2000-07-06	LHRH antagonist peptides

Legal Events

Date	Code	Title	Description
1999-07-02	FZDE	Dead