BG107121A - Нови lhrh-антагонисти, тяхното получаване и използване като лекарственo средствo - Google Patents

Нови lhrh-антагонисти, тяхното получаване и използване като лекарственo средствo Download PDF

Info

Publication number: BG107121A
Authority: BG; Bulgaria
Prior art keywords: xxx; liz; hfa; nle; nal
Prior art date: 2000-03-14

Application number

BG107121A

Other languages

Bulgarian (bg)

English (en)

Inventor

Michael Bernd

Bernhard Kutscher

Eckhard Gunther

Peter Romeis

Thomas Reissmann

Thomas Beckers

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.)

2000-03-14

Filing date

2002-09-18

Publication date

2003-05-30

2000-03-14 Priority claimed from US09/525,007 external-priority patent/US6627609B1/en

2002-09-18 Application filed by Zentaris Gmbh filed Critical Zentaris Gmbh

2003-05-30 Publication of BG107121A publication Critical patent/BG107121A/bg

Links

239000003814 drug Substances 0.000 title claims abstract description 11
229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 title description 5
238000011282 treatment Methods 0.000 claims abstract description 17
229940088597 hormone Drugs 0.000 claims abstract description 14
239000005556 hormone Substances 0.000 claims abstract description 14
230000001419 dependent effect Effects 0.000 claims abstract description 8
206010028980 Neoplasm Diseases 0.000 claims abstract description 7
230000003211 malignant effect Effects 0.000 claims abstract description 7
201000010099 disease Diseases 0.000 claims abstract description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 52
238000000034 method Methods 0.000 claims description 45
-1 4-amidinophenyl Chemical group 0.000 claims description 21
239000002253 acid Substances 0.000 claims description 20
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 17
150000007513 acids Chemical class 0.000 claims description 12
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
239000012634 fragment Substances 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 6
201000009273 Endometriosis Diseases 0.000 claims description 6
208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 6
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 6
239000007790 solid phase Substances 0.000 claims description 6
206010060862 Prostate cancer Diseases 0.000 claims description 5
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
206010046798 Uterine leiomyoma Diseases 0.000 claims description 5
208000021267 infertility disease Diseases 0.000 claims description 5
239000000203 mixture Substances 0.000 claims description 5
230000001629 suppression Effects 0.000 claims description 5
206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 4
239000000969 carrier Substances 0.000 claims description 4
238000005304 joining Methods 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
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 3
241000282322 Panthera Species 0.000 claims description 2
241000282320 Panthera leo Species 0.000 claims description 2
101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims description 2
230000009435 amidation Effects 0.000 claims description 2
238000007112 amidation reaction Methods 0.000 claims description 2
210000000481 breast Anatomy 0.000 claims description 2
239000002552 dosage form Substances 0.000 claims description 2
229950005627 embonate Drugs 0.000 claims description 2
238000002156 mixing Methods 0.000 claims description 2
239000006104 solid solution Substances 0.000 claims description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
101000904177 Clupea pallasii Gonadoliberin-1 Proteins 0.000 claims 1
108090000765 processed proteins & peptides Proteins 0.000 abstract description 39
150000001413 amino acids Chemical class 0.000 abstract description 23
102000004196 processed proteins & peptides Human genes 0.000 abstract description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
229940024606 amino acid Drugs 0.000 description 25
235000001014 amino acid Nutrition 0.000 description 25
108700012941 GNRH1 Proteins 0.000 description 16
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
125000006239 protecting group Chemical group 0.000 description 15
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
229920005989 resin Polymers 0.000 description 13
239000011347 resin Substances 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
238000005406 washing Methods 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 12
239000000243 solution Substances 0.000 description 11
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 10
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 10
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 description 10
BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 10
239000004472 Lysine Substances 0.000 description 9
239000005557 antagonist Substances 0.000 description 9
229960003230 cetrorelix Drugs 0.000 description 9
238000009833 condensation Methods 0.000 description 9
230000005494 condensation Effects 0.000 description 9
108700008462 cetrorelix Proteins 0.000 description 8
238000012360 testing method Methods 0.000 description 8
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 7
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
238000003776 cleavage reaction Methods 0.000 description 7
230000007017 scission Effects 0.000 description 7
238000010532 solid phase synthesis reaction Methods 0.000 description 7
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000002904 solvent Substances 0.000 description 6
KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
238000010276 construction Methods 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
238000011068 loading method Methods 0.000 description 5
238000010647 peptide synthesis reaction Methods 0.000 description 5
239000000047 product Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
102100024028 Progonadoliberin-1 Human genes 0.000 description 4
101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
JMKBTQYGOKJMBJ-ZQPPIKFSSA-N bacteriohopane-32,33,34,35-tetrol Chemical compound C([C@]1(C)[C@H]2CC[C@H]34)CCC(C)(C)[C@@H]1CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@@H]1[C@@H](CC[C@@H](O)[C@@H](O)[C@@H](O)CO)C JMKBTQYGOKJMBJ-ZQPPIKFSSA-N 0.000 description 4
NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 description 4
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
238000010265 fast atom bombardment Methods 0.000 description 4
XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)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 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 4
235000010355 mannitol Nutrition 0.000 description 4
239000000463 material Substances 0.000 description 4
230000003389 potentiating effect Effects 0.000 description 4
238000000859 sublimation Methods 0.000 description 4
230000008022 sublimation Effects 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
NOENHWMKHNSHGX-IZOOSHNJSA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-(ca Chemical compound C([C@H](C(=O)N[C@H](CCCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 NOENHWMKHNSHGX-IZOOSHNJSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
230000009471 action Effects 0.000 description 3
108010070670 antarelix Proteins 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 3
239000005516 coenzyme A Substances 0.000 description 3
229940093530 coenzyme a Drugs 0.000 description 3
KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 3
238000004108 freeze drying Methods 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
238000011534 incubation Methods 0.000 description 3
CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 3
SHDMMLFAFLZUEV-UHFFFAOYSA-N n-methyl-1,1-diphenylmethanamine Chemical compound C=1C=CC=CC=1C(NC)C1=CC=CC=C1 SHDMMLFAFLZUEV-UHFFFAOYSA-N 0.000 description 3
239000008188 pellet Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
229960001153 serine Drugs 0.000 description 3
239000007787 solid Substances 0.000 description 3
MVDPNTCYCFVFOX-SZENRQNHSA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-iodanylphenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(c Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC([125I])=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 MVDPNTCYCFVFOX-SZENRQNHSA-N 0.000 description 2
MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
239000004475 Arginine Substances 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical class NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
FBPFZTCFMRRESA-BXKVDMCESA-N L-mannitol Chemical compound OC[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO FBPFZTCFMRRESA-BXKVDMCESA-N 0.000 description 2
229930182842 L-mannitol Natural products 0.000 description 2
102000008238 LHRH Receptors Human genes 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
239000004473 Threonine Substances 0.000 description 2
150000001242 acetic acid derivatives Chemical class 0.000 description 2
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
125000000539 amino acid group Chemical group 0.000 description 2
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
229910052796 boron Inorganic materials 0.000 description 2
229940098773 bovine serum albumin Drugs 0.000 description 2
150000001718 carbodiimides Chemical class 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000012050 conventional carrier Substances 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
230000005714 functional activity Effects 0.000 description 2
239000011521 glass Substances 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
230000009027 insemination Effects 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000002609 medium Substances 0.000 description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
210000000287 oocyte Anatomy 0.000 description 2
230000002611 ovarian Effects 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
229920005990 polystyrene resin Polymers 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000008569 process Effects 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000001525 receptor binding assay Methods 0.000 description 2
239000004576 sand Substances 0.000 description 2
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical group C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
238000000926 separation method Methods 0.000 description 2
229960002920 sorbitol Drugs 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
ZELBLMDUXBNUSM-LBPRGKRZSA-N (2s)-2-amino-3-naphthalen-2-yloxypropanoic acid Chemical compound C1=CC=CC2=CC(OC[C@H](N)C(O)=O)=CC=C21 ZELBLMDUXBNUSM-LBPRGKRZSA-N 0.000 description 1
DFZVZEMNPGABKO-ZETCQYMHSA-N (2s)-2-amino-3-pyridin-3-ylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CN=C1 DFZVZEMNPGABKO-ZETCQYMHSA-N 0.000 description 1
VXEOCBVZFIXWQA-UHFFFAOYSA-N 1,2,3-tris(benzenesulfonyl)benzene Chemical group C1(=CC=CC=C1)S(=O)(=O)C=1C(=C(C=CC=1)S(=O)(=O)C1=CC=CC=C1)S(=O)(=O)C1=CC=CC=C1 VXEOCBVZFIXWQA-UHFFFAOYSA-N 0.000 description 1
DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
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 1
YMSZFQVDZUKSFV-UHFFFAOYSA-N 2-[4-[amino-(2,4-dimethoxyphenyl)methyl]phenoxy]acetic acid Chemical compound COC1=CC(OC)=CC=C1C(N)C1=CC=C(OCC(O)=O)C=C1 YMSZFQVDZUKSFV-UHFFFAOYSA-N 0.000 description 1
HRGUSFBJBOKSML-UHFFFAOYSA-N 3',5'-di-O-methyltricetin Chemical compound COC1=C(O)C(OC)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 HRGUSFBJBOKSML-UHFFFAOYSA-N 0.000 description 1
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
108010001478 Bacitracin Proteins 0.000 description 1
229920000742 Cotton Polymers 0.000 description 1
IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
125000000030 D-alanine group Chemical group [H]N([H])[C@](C([H])([H])[H])(C(=O)[*])[H] 0.000 description 1
ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 1
CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
NIGWMJHCCYYCSF-UHFFFAOYSA-N Fenclonine Chemical compound OC(=O)C(N)CC1=CC=C(Cl)C=C1 NIGWMJHCCYYCSF-UHFFFAOYSA-N 0.000 description 1
BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
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 description 1
108050000048 Gonadoliberin Proteins 0.000 description 1
102000009165 Gonadoliberin Human genes 0.000 description 1
102400000932 Gonadoliberin-1 Human genes 0.000 description 1
101100229685 Homo sapiens GNRH1 gene Proteins 0.000 description 1
101500026183 Homo sapiens Gonadoliberin-1 Proteins 0.000 description 1
101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
108010021290 LHRH Receptors Proteins 0.000 description 1
241000131894 Lampyris noctiluca Species 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
VIHYIVKEECZGOU-UHFFFAOYSA-N N-acetylimidazole Chemical compound CC(=O)N1C=CN=C1 VIHYIVKEECZGOU-UHFFFAOYSA-N 0.000 description 1
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
239000005662 Paraffin oil Substances 0.000 description 1
241000254064 Photinus pyralis Species 0.000 description 1
IDDMFNIRSJVBHE-UHFFFAOYSA-N Piscigenin Natural products COC1=C(O)C(OC)=CC(C=2C(C3=C(O)C=C(O)C=C3OC=2)=O)=C1 IDDMFNIRSJVBHE-UHFFFAOYSA-N 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
108700008625 Reporter Genes Proteins 0.000 description 1
239000012891 Ringer solution Substances 0.000 description 1
101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
108010077895 Sarcosine Proteins 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
101710162629 Trypsin inhibitor Proteins 0.000 description 1
229940122618 Trypsin inhibitor Drugs 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
159000000021 acetate salts Chemical class 0.000 description 1
108700023965 acetyl-2-(2-naphthyl)-Ala(1)-4-F-Phe(2)-Trp(3)-Arg(6)- LHRH Proteins 0.000 description 1
CQJZXVCPROCGRM-OYDHUGEGSA-N acetyl-2-(2-naphthyl)-ala(1)-4-f-phe(2)-trp(3)-arg(6)-lhrh Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=N)C(=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=1C=CC(F)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 CQJZXVCPROCGRM-OYDHUGEGSA-N 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
125000003275 alpha amino acid group Chemical group 0.000 description 1
150000003862 amino acid derivatives Chemical class 0.000 description 1
238000007098 aminolysis reaction Methods 0.000 description 1
239000012491 analyte Substances 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
229960003071 bacitracin Drugs 0.000 description 1
229930184125 bacitracin Natural products 0.000 description 1
CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
239000012148 binding buffer Substances 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 1
239000000470 constituent Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
YGLLICRFEVEWOZ-UHFFFAOYSA-L disodium;3-carboxy-1-[(3-carboxy-2-oxidonaphthalen-1-yl)methyl]naphthalen-2-olate Chemical compound [Na+].[Na+].C1=CC=C2C(CC3=C4C=CC=CC4=CC(=C3O)C([O-])=O)=C(O)C(C([O-])=O)=CC2=C1 YGLLICRFEVEWOZ-UHFFFAOYSA-L 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000003480 eluent Substances 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
230000029142 excretion Effects 0.000 description 1
230000004720 fertilization Effects 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
239000011152 fibreglass Substances 0.000 description 1
125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
238000011990 functional testing Methods 0.000 description 1
108700032141 ganirelix Proteins 0.000 description 1
GJNXBNATEDXMAK-PFLSVRRQSA-N ganirelix Chemical compound C([C@@H](C(=O)N[C@H](CCCCN=C(NCC)NCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN=C(NCC)NCC)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 GJNXBNATEDXMAK-PFLSVRRQSA-N 0.000 description 1
229960003794 ganirelix Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
229960001442 gonadorelin Drugs 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
CBCIHIVRDWLAME-UHFFFAOYSA-N hexanitrodiphenylamine Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1NC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O CBCIHIVRDWLAME-UHFFFAOYSA-N 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
238000004020 luminiscence type Methods 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical class [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
239000003921 oil Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000011049 pearl Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
230000002028 premature Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
238000011002 quantification Methods 0.000 description 1
230000006340 racemization Effects 0.000 description 1
238000000611 regression analysis Methods 0.000 description 1
238000003571 reporter gene assay Methods 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
230000036185 rubor Effects 0.000 description 1
229940043230 sarcosine Drugs 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
229920002545 silicone oil Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
229950011372 teverelix Drugs 0.000 description 1
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
BMCJATLPEJCACU-UHFFFAOYSA-N tricin Natural products COc1cc(OC)c(O)c(c1)C2=CC(=O)c3c(O)cc(O)cc3O2 BMCJATLPEJCACU-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=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 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
229960004824 triptorelin Drugs 0.000 description 1
JLEXUIVKURIPFI-UHFFFAOYSA-N tris phosphate Chemical compound OP(O)(O)=O.OCC(N)(CO)CO JLEXUIVKURIPFI-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
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 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
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 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 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
- 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
- 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
- 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
- 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
- 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
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Endocrinology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Genetics & Genomics (AREA)
Reproductive Health (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Pregnancy & Childbirth (AREA)
Gynecology & Obstetrics (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

BG107121A 2000-03-14 2002-09-18 Нови lhrh-антагонисти, тяхното получаване и използване като лекарственo средствo BG107121A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US09/525,007 US6627609B1 (en)	1999-03-17	2000-03-14	LHRH antagonists having improved solubility properties
PCT/EP2001/002719 WO2001068676A2 (fr)	2000-03-14	2001-03-12	Nouveaux antagonistes de la lhrh, sa production et son utilisation comme medicament

Publications (1)

Publication Number	Publication Date
BG107121A true BG107121A (bg)	2003-05-30

Family

ID=24091545

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG107121A BG107121A (bg)	2000-03-14	2002-09-18	Нови lhrh-антагонисти, тяхното получаване и използване като лекарственo средствo

Country Status (25)

Country	Link
EP (1)	EP1268522B1 (fr)
JP (1)	JP3805679B2 (fr)
KR (1)	KR100607396B1 (fr)
CN (2)	CN100500692C (fr)
AT (1)	ATE408619T1 (fr)
AU (2)	AU6011001A (fr)
BG (1)	BG107121A (fr)
BR (1)	BR0109279A (fr)
CA (1)	CA2402193C (fr)
DE (1)	DE50114335D1 (fr)
DK (1)	DK1268522T3 (fr)
ES (1)	ES2312435T3 (fr)
HR (1)	HRP20020810A2 (fr)
HU (1)	HUP0300222A3 (fr)
IL (1)	IL151647A0 (fr)
MX (1)	MXPA02008870A (fr)
NO (1)	NO20024363L (fr)
NZ (1)	NZ521273A (fr)
PL (1)	PL357999A1 (fr)
PT (1)	PT1268522E (fr)
RU (1)	RU2248982C9 (fr)
SK (1)	SK14332002A3 (fr)
UA (1)	UA79070C2 (fr)
WO (1)	WO2001068676A2 (fr)
ZA (1)	ZA200207248B (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN100340572C (zh) *	2004-12-01	2007-10-03	中国人民解放军军事医学科学院毒物药物研究所	新的lhrh拮抗剂
CN101037472B (zh) *	2006-03-14	2013-03-27	中国人民解放军军事医学科学院毒物药物研究所	具有低组胺释放作用的促黄体生成素释放激素拮抗剂
KR101863136B1 (ko)	2008-01-24	2018-05-31	에스퍼란스 파마슈티컬스, 인코포레이티드	용해 도메인 융합 구성물 및 이를 제조하고 사용하는 방법
TWI539959B (zh) *	2008-02-11	2016-07-01	菲瑞茵國際中心股份有限公司	治療轉移階段攝護腺癌的方法
CN101597321B (zh) *	2008-06-03	2013-04-24	中国人民解放军军事医学科学院毒物药物研究所	长效低组胺释放副作用的lhrh拮抗剂
WO2010142060A1 (fr) *	2009-06-11	2010-12-16	中国人民解放军军事医学科学院毒物药物研究所	Antagoniste de la lhrh à longue durée d'action et faible effet de libération d'histamine
IL238323B2 (en)	2012-10-30	2023-11-01	Esperance Pharmaceuticals Inc	Antibody/drug conjugates and methods of use
CN104418936B (zh) *	2013-08-20	2018-06-05	中国人民解放军军事医学科学院毒物药物研究所	Lhrh拮抗剂衍生物及其药物用途
FR3024612B1 (fr) *	2014-08-04	2018-03-09	Alstom Transp Tech	Module d'alimentation electrique d'un bloc moteur, systeme de traction et vehicule electrique associe
RU2585367C1 (ru) *	2014-11-05	2016-05-27	Наталья Владимировна Спиридонова	Способ лечения бесплодия у женщин с миомой матки

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ZA862570B (en) *	1985-04-09	1986-12-30	Univ Tulane	Therapeutic decapeptides
US5110904A (en) *	1989-08-07	1992-05-05	Abbott Laboratories	Lhrh analogs
US5300492A (en)	1988-02-10	1994-04-05	Tap Pharmaceuticals	LHRH analogs
US5140009A (en)	1988-02-10	1992-08-18	Tap Pharmaceuticals, Inc.	Octapeptide LHRH antagonists
IL101074A (en)	1991-03-14	1997-09-30	Salk Inst For Biological Studi	GnRH ANALOGS AND THEIR PREPARATION
DE69214818T2 (de)	1991-04-25	1997-02-27	Romano S.-Cergue Deghenghi	LHRH-Antagonisten
RU2043362C1 (ru) *	1991-08-12	1995-09-10	Синтекс (Ю-Эс-Эй) Инк.	Способ твердофазного синтеза пептидов
JPH08504209A (ja)	1992-12-04	1996-05-07	アボツト・ラボラトリーズ	６位修飾デカペプチドｌｈｒｈ拮抗薬
CA2136079A1 (fr)	1992-12-18	1994-07-07	Fortuna Haviv	Antagonistes de lhrh presentant des residus aminoacyle modifies en position 5 et 6
IL108509A0 (en)	1993-02-22	1994-05-30	Salk Inst For Biological Studi	GnRH antagonist peptides
DE4320201A1 (de) *	1993-06-18	1995-01-12	Asta Medica Ag	Verwendung von Cetrorelix und weiteren Nona- und Dekapeptiden zur Herstellung eines Arzneimittels zur Bekämpfung von Aids und zur Wachstumsstimulation
DE19544212A1 (de)	1995-11-28	1997-06-05	Asta Medica Ag	Neue LH-RH-Antagonisten mit verbesserter Wirkung
DE19911771B4 (de) *	1999-03-17	2006-03-30	Zentaris Gmbh	LHRH-Antagonist, Verfahren zu seiner Herstellung und seiner Verwendung

2001
- 2001-03-12 CN CNB2006100817821A patent/CN100500692C/zh not_active Expired - Fee Related
- 2001-03-12 DK DK01933682T patent/DK1268522T3/da active
- 2001-03-12 PL PL01357999A patent/PL357999A1/xx unknown
- 2001-03-12 EP EP01933682A patent/EP1268522B1/fr not_active Expired - Lifetime
- 2001-03-12 DE DE50114335T patent/DE50114335D1/de not_active Expired - Fee Related
- 2001-03-12 WO PCT/EP2001/002719 patent/WO2001068676A2/fr not_active Ceased
- 2001-03-12 PT PT01933682T patent/PT1268522E/pt unknown
- 2001-03-12 MX MXPA02008870A patent/MXPA02008870A/es active IP Right Grant
- 2001-03-12 HR HRP20020810 patent/HRP20020810A2/hr not_active Application Discontinuation
- 2001-03-12 CA CA2402193A patent/CA2402193C/fr not_active Expired - Lifetime
- 2001-03-12 BR BR0109279-0A patent/BR0109279A/pt not_active IP Right Cessation
- 2001-03-12 NZ NZ521273A patent/NZ521273A/en unknown
- 2001-03-12 AU AU6011001A patent/AU6011001A/xx active Pending
- 2001-03-12 KR KR1020027012059A patent/KR100607396B1/ko not_active Expired - Lifetime
- 2001-03-12 RU RU2002127786/04A patent/RU2248982C9/ru active
- 2001-03-12 IL IL15164701A patent/IL151647A0/xx unknown
- 2001-03-12 JP JP2001567766A patent/JP3805679B2/ja not_active Expired - Lifetime
- 2001-03-12 HU HU0300222A patent/HUP0300222A3/hu unknown
- 2001-03-12 AU AU2001260110A patent/AU2001260110B2/en not_active Ceased
- 2001-03-12 CN CN01807543A patent/CN1443195A/zh active Pending
- 2001-03-12 SK SK1433-2002A patent/SK14332002A3/sk not_active Application Discontinuation
- 2001-03-12 ES ES01933682T patent/ES2312435T3/es not_active Expired - Lifetime
- 2001-03-12 AT AT01933682T patent/ATE408619T1/de not_active IP Right Cessation
- 2001-12-03 UA UA2002108075A patent/UA79070C2/uk unknown
2002
- 2002-09-10 ZA ZA200207248A patent/ZA200207248B/en unknown
- 2002-09-12 NO NO20024363A patent/NO20024363L/no not_active Application Discontinuation
- 2002-09-18 BG BG107121A patent/BG107121A/bg unknown

Also Published As

Publication number	Publication date
NO20024363D0 (no)	2002-09-12
RU2248982C2 (ru)	2005-03-27
WO2001068676A2 (fr)	2001-09-20
NZ521273A (en)	2005-01-28
UA79070C2 (en)	2007-05-25
BR0109279A (pt)	2002-12-17
ZA200207248B (en)	2003-02-21
ATE408619T1 (de)	2008-10-15
CA2402193C (fr)	2010-05-18
EP1268522A2 (fr)	2003-01-02
DK1268522T3 (da)	2009-01-12
KR100607396B1 (ko)	2006-08-02
ES2312435T3 (es)	2009-03-01
HUP0300222A2 (hu)	2003-07-28
CA2402193A1 (fr)	2002-09-09
SK14332002A3 (sk)	2003-09-11
PT1268522E (pt)	2008-12-22
RU2248982C9 (ru)	2005-06-10
AU2001260110B2 (en)	2005-05-05
HUP0300222A3 (en)	2004-08-30
HRP20020810A2 (en)	2004-12-31
KR20020083179A (ko)	2002-11-01
DE50114335D1 (de)	2008-10-30
MXPA02008870A (es)	2003-06-24
JP2003535044A (ja)	2003-11-25
JP3805679B2 (ja)	2006-08-02
CN1443195A (zh)	2003-09-17
EP1268522B1 (fr)	2008-09-17
PL357999A1 (en)	2004-08-09
AU6011001A (en)	2001-09-24
WO2001068676A3 (fr)	2002-10-24
CN100500692C (zh)	2009-06-17
CN1876677A (zh)	2006-12-13
IL151647A0 (en)	2003-04-10
NO20024363L (no)	2002-11-13

Publication	Publication Date	Title
DE3850789T2 (de)	1995-03-09	Nonapeptid- und Dekapeptid-Analoge von LHRH, die als LHRH-Antagonisten dienen.
JP2944669B2 (ja)	1999-09-06	ペプチド、その製造法、該ペプチドを含有する、ｌｈｒｈ拮抗剤
DK171483B1 (da)	1996-11-25	Aminosyrederivater
AU759442B2 (en)	2003-04-17	Novel LHRH antagonists with improved solubility characteristics
JPS61122297A (ja)	1986-06-10	新規ハロ低級アルキルグアニジノ置換アミノ酸化合物およびその製法
WO1995004540A1 (fr)	1995-02-16	Analogues modifies de l'hormone liberant l'hormone luteinisante (lhrh) a extremite n-terminale
BG107121A (bg)	2003-05-30	Нови lhrh-антагонисти, тяхното получаване и използване като лекарственo средствo
HU208159B (en)	1993-08-30	Process for producing 1h-rh analogs and pharmaceutical compositions comprising same
BG64386B1 (bg)	2004-12-30	Нови lн-rн-антагонисти с подобрено действие
JPS63303999A (ja)	1988-12-12	バソプレシン拮抗剤
HK1057569A (en)	2004-04-08	Novel lhrh-antagonists, production and use thereof as medicament