UA68407C2 - Antagonistic analogues of growth hormone releasing hormone (gh-rh) inhibiting activity of endogenous insulin-like growth factors - Google Patents

Antagonistic analogues of growth hormone releasing hormone (gh-rh) inhibiting activity of endogenous insulin-like growth factors Download PDF

Info

Publication number: UA68407C2
Authority: UA; Ukraine
Prior art keywords: peptide; ago; aby; nag; compound according
Prior art date: 1998-11-25

Application number

UA2001064393A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Univ Tulane

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.)

1998-11-25

Filing date

1999-11-23

Publication date

2004-08-16

1999-11-23 Application filed by Univ Tulane filed Critical Univ Tulane

2004-08-16 Publication of UA68407C2 publication Critical patent/UA68407C2/uk

Links

230000002401 inhibitory effect Effects 0.000 title claims abstract description 10
108090000723 Insulin-Like Growth Factor I Proteins 0.000 title claims description 8
102000013275 Somatomedins Human genes 0.000 title claims 2
230000003042 antagnostic effect Effects 0.000 title description 16
102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 title 1
239000000095 Growth Hormone-Releasing Hormone Substances 0.000 title 1
101710142969 Somatoliberin Proteins 0.000 title 1
102000018997 Growth Hormone Human genes 0.000 claims abstract description 12
108010051696 Growth Hormone Proteins 0.000 claims abstract description 12
239000000122 growth hormone Substances 0.000 claims abstract description 12
108090000765 processed proteins & peptides Proteins 0.000 claims description 159
206010028980 Neoplasm Diseases 0.000 claims description 53
101710176384 Peptide 1 Proteins 0.000 claims description 22
OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 claims description 21
201000011510 cancer Diseases 0.000 claims description 17
150000001875 compounds Chemical class 0.000 claims description 16
238000000034 method Methods 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 7
239000003488 releasing hormone Substances 0.000 claims description 3
108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 2
102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 2
108020004999 messenger RNA Proteins 0.000 claims description 2
238000012876 topography Methods 0.000 claims 1
150000001413 amino acids Chemical class 0.000 abstract description 48
230000000694 effects Effects 0.000 abstract description 17
230000036515 potency Effects 0.000 abstract 1
239000005557 antagonist Substances 0.000 description 68
235000001014 amino acid Nutrition 0.000 description 44
102000004196 processed proteins & peptides Human genes 0.000 description 39
238000009739 binding Methods 0.000 description 30
229920005989 resin Polymers 0.000 description 27
239000011347 resin Substances 0.000 description 27
241000699670 Mus sp. Species 0.000 description 24
230000027455 binding Effects 0.000 description 24
125000006239 protecting group Chemical group 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
-1 9-fluorenylmethyloxycarbonyl Chemical group 0.000 description 17
230000005764 inhibitory process Effects 0.000 description 17
230000015572 biosynthetic process Effects 0.000 description 16
238000003786 synthesis reaction Methods 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
238000004128 high performance liquid chromatography Methods 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
241000700159 Rattus Species 0.000 description 11
125000000539 amino acid group Chemical group 0.000 description 11
238000002347 injection Methods 0.000 description 11
239000007924 injection Substances 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
201000010099 disease Diseases 0.000 description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
238000004519 manufacturing process Methods 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
229910000040 hydrogen fluoride Inorganic materials 0.000 description 9
239000000203 mixture Substances 0.000 description 9
239000012071 phase Substances 0.000 description 9
241001465754 Metazoa Species 0.000 description 8
238000004458 analytical method Methods 0.000 description 8
125000000524 functional group Chemical group 0.000 description 8
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 8
UHPQFNXOFFPHJW-UHFFFAOYSA-N (4-methylphenyl)-phenylmethanamine Chemical compound C1=CC(C)=CC=C1C(N)C1=CC=CC=C1 UHPQFNXOFFPHJW-UHFFFAOYSA-N 0.000 description 7
206010062767 Hypophysitis Diseases 0.000 description 7
241001190694 Muda Species 0.000 description 7
230000009471 action Effects 0.000 description 7
230000003305 autocrine Effects 0.000 description 7
230000012010 growth Effects 0.000 description 7
108010005636 polypeptide C Proteins 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
230000004044 response Effects 0.000 description 7
238000010532 solid phase synthesis reaction Methods 0.000 description 7
210000001519 tissue Anatomy 0.000 description 7
230000004614 tumor growth Effects 0.000 description 7
FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 6
210000003635 pituitary gland Anatomy 0.000 description 6
239000007790 solid phase Substances 0.000 description 6
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
206010006187 Breast cancer Diseases 0.000 description 5
208000026310 Breast neoplasm Diseases 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
102000005157 Somatostatin Human genes 0.000 description 5
108010056088 Somatostatin Proteins 0.000 description 5
125000003277 amino group Chemical group 0.000 description 5
239000008280 blood Substances 0.000 description 5
210000004369 blood Anatomy 0.000 description 5
239000012634 fragment Substances 0.000 description 5
230000036210 malignancy Effects 0.000 description 5
239000000047 product Substances 0.000 description 5
230000035755 proliferation Effects 0.000 description 5
210000002307 prostate Anatomy 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000000243 solution Substances 0.000 description 5
229960000553 somatostatin Drugs 0.000 description 5
238000012360 testing method Methods 0.000 description 5
206010000599 Acromegaly Diseases 0.000 description 4
206010060862 Prostate cancer Diseases 0.000 description 4
208000000236 Prostatic Neoplasms Diseases 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
210000001072 colon Anatomy 0.000 description 4
239000007788 liquid Substances 0.000 description 4
210000005075 mammary gland Anatomy 0.000 description 4
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 4
230000003076 paracrine Effects 0.000 description 4
239000002245 particle Substances 0.000 description 4
238000010647 peptide synthesis reaction Methods 0.000 description 4
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 4
239000011148 porous material Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
238000003127 radioimmunoassay Methods 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
VZQHRKZCAZCACO-PYJNHQTQSA-N (2s)-2-[[(2s)-2-[2-[[(2s)-2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]prop-2-enoylamino]-3-methylbutanoyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)C(=C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCNC(N)=N VZQHRKZCAZCACO-PYJNHQTQSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
125000001433 C-terminal amino-acid group Chemical group 0.000 description 3
206010009944 Colon cancer Diseases 0.000 description 3
208000007342 Diabetic Nephropathies Diseases 0.000 description 3
206010012689 Diabetic retinopathy Diseases 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
210000000481 breast Anatomy 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
208000029742 colonic neoplasm Diseases 0.000 description 3
230000006378 damage Effects 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
208000033679 diabetic kidney disease Diseases 0.000 description 3
239000003480 eluent Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
238000004108 freeze drying Methods 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
238000010829 isocratic elution Methods 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
230000003211 malignant effect Effects 0.000 description 3
239000012528 membrane Substances 0.000 description 3
239000003094 microcapsule Substances 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
230000003204 osmotic effect Effects 0.000 description 3
230000001817 pituitary effect Effects 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
238000011160 research Methods 0.000 description 3
101150006605 rpa gene Proteins 0.000 description 3
230000028327 secretion Effects 0.000 description 3
239000007929 subcutaneous injection Substances 0.000 description 3
238000010254 subcutaneous injection Methods 0.000 description 3
230000001629 suppression Effects 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
238000002054 transplantation Methods 0.000 description 3
RWLSBXBFZHDHHX-VIFPVBQESA-N (2s)-2-(naphthalen-2-ylamino)propanoic acid Chemical compound C1=CC=CC2=CC(N[C@@H](C)C(O)=O)=CC=C21 RWLSBXBFZHDHHX-VIFPVBQESA-N 0.000 description 2
JPOKAKNGULMYHZ-UILVTTEASA-N (2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-6-amino-2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-3-(4-hydroxyp Chemical compound C([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N)C1=CC=C(O)C=C1 JPOKAKNGULMYHZ-UILVTTEASA-N 0.000 description 2
MUSGYEMSJUFFHT-UWABRSFTSA-N 2-[(4R,7S,10S,13S,19S,22S,25S,28S,31S,34R)-34-[[(2S,3S)-2-[[(2R)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]-methylcarbamoyl]-25-(3-amino-3-oxopropyl)-7-(3-carbamimidamidopropyl)-10-(1H-imidazol-5-ylmethyl)-19-(1H-indol-3-ylmethyl)-13,17-dimethyl-28-[(1-methylindol-3-yl)methyl]-6,9,12,15,18,21,24,27,30,33-decaoxo-31-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29,32-decazacyclopentatriacont-22-yl]acetic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](N)Cc1ccc(O)cc1)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](C)NC(=O)CN(C)C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2cn(C)c3ccccc23)NC(=O)[C@@H](NC1=O)C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)C(N)=O MUSGYEMSJUFFHT-UWABRSFTSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
201000004569 Blindness Diseases 0.000 description 2
208000003174 Brain Neoplasms Diseases 0.000 description 2
241000282412 Homo Species 0.000 description 2
RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 2
RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 2
108091034117 Oligonucleotide Proteins 0.000 description 2
102000006382 Ribonucleases Human genes 0.000 description 2
108010083644 Ribonucleases Proteins 0.000 description 2
108050001286 Somatostatin Receptor Proteins 0.000 description 2
102000011096 Somatostatin receptor Human genes 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
230000001270 agonistic effect Effects 0.000 description 2
230000000259 anti-tumor effect Effects 0.000 description 2
229920002988 biodegradable polymer Polymers 0.000 description 2
239000004621 biodegradable polymer Substances 0.000 description 2
238000004590 computer program Methods 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000001914 filtration Methods 0.000 description 2
125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
210000003016 hypothalamus Anatomy 0.000 description 2
239000007943 implant Substances 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
230000005923 long-lasting effect Effects 0.000 description 2
230000007774 longterm Effects 0.000 description 2
208000029565 malignant colon neoplasm Diseases 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
210000003205 muscle Anatomy 0.000 description 2
238000006386 neutralization reaction Methods 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
201000008968 osteosarcoma Diseases 0.000 description 2
210000000496 pancreas Anatomy 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
229960003424 phenylacetic acid Drugs 0.000 description 2
239000003279 phenylacetic acid Substances 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000002685 pulmonary effect Effects 0.000 description 2
230000009467 reduction Effects 0.000 description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 1
HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 1
SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
208000018084 Bone neoplasm Diseases 0.000 description 1
108010075254 C-Peptide Proteins 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
241000219112 Cucumis Species 0.000 description 1
235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
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 1
QWCKQJZIFLGMSD-GSVOUGTGSA-N D-alpha-aminobutyric acid Chemical compound CC[C@@H](N)C(O)=O QWCKQJZIFLGMSD-GSVOUGTGSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-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
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
101000825742 Homo sapiens Somatoliberin Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
208000008839 Kidney Neoplasms Diseases 0.000 description 1
QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
206010064912 Malignant transformation Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241000343235 Maso Species 0.000 description 1
229920001367 Merrifield resin Polymers 0.000 description 1
241001529936 Murinae Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
AWZVYNHQGTZJIH-UHFFFAOYSA-N N-Nitrosomethylvinylamine Chemical compound C=CN(C)N=O AWZVYNHQGTZJIH-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
229910019142 PO4 Inorganic materials 0.000 description 1
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
229910020163 SiOCl Inorganic materials 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
229920002253 Tannate Polymers 0.000 description 1
GFBKORZTTCHDGY-UWVJOHFNSA-N Thiothixene Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2SC2=CC=CC=C2\C1=C\CCN1CCN(C)CC1 GFBKORZTTCHDGY-UWVJOHFNSA-N 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
102000030621 adenylate cyclase Human genes 0.000 description 1
108060000200 adenylate cyclase Proteins 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000008901 benefit Effects 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-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
230000037396 body weight Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
210000003557 bones of lower extremity Anatomy 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000008859 change Effects 0.000 description 1
VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
229960002173 citrulline Drugs 0.000 description 1
235000013477 citrulline Nutrition 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
230000009137 competitive binding Effects 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
210000002808 connective tissue Anatomy 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000001066 destructive effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
150000001993 dienes Chemical class 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
210000003054 facial bone Anatomy 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
208000005017 glioblastoma Diseases 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
244000144993 groups of animals Species 0.000 description 1
230000009036 growth inhibition Effects 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
238000010562 histological examination Methods 0.000 description 1
102000045304 human GHRH Human genes 0.000 description 1
238000011534 incubation Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
210000004731 jugular vein Anatomy 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
230000004130 lipolysis Effects 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
229940049920 malate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
230000036212 malign transformation Effects 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
230000037353 metabolic pathway Effects 0.000 description 1
CSHFHJNMIMPJST-HOTGVXAUSA-N methyl (2s)-2-[[(2s)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoate Chemical compound NCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)OC)CC1=CC=CC=C1 CSHFHJNMIMPJST-HOTGVXAUSA-N 0.000 description 1
MWZPENIJLUWBSY-VIFPVBQESA-N methyl L-tyrosinate Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWZPENIJLUWBSY-VIFPVBQESA-N 0.000 description 1
239000003226 mitogen Substances 0.000 description 1
230000017074 necrotic cell death Effects 0.000 description 1
229940105631 nembutal Drugs 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000001668 nucleic acid synthesis Methods 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
230000000771 oncological effect Effects 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
101800002712 p27 Proteins 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
239000002952 polymeric resin Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000008569 process Effects 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000001243 protein synthesis Methods 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
230000000541 pulsatile effect Effects 0.000 description 1
230000006340 racemization Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
210000001525 retina Anatomy 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000013049 sediment Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
210000002356 skeleton Anatomy 0.000 description 1
208000000649 small cell carcinoma Diseases 0.000 description 1
239000007787 solid Substances 0.000 description 1
229940075620 somatostatin analogue Drugs 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
229920003002 synthetic resin Polymers 0.000 description 1
229940095064 tartrate Drugs 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
229940104230 thymidine Drugs 0.000 description 1
230000014616 translation Effects 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1

Classifications

- 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
- C07K14/575—Hormones
- C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- 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
- 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
- A61P5/08—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
- 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)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Endocrinology (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Toxicology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)

UA2001064393A 1998-11-25 1999-11-23 Antagonistic analogues of growth hormone releasing hormone (gh-rh) inhibiting activity of endogenous insulin-like growth factors UA68407C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US09/199,381 US6057422A (en)	1998-11-25	1998-11-25	Antagonistic analogs of GH-RH inhibiting IGF-I and -II
PCT/US1999/027822 WO2000031136A1 (en)	1998-11-25	1999-11-23	Antagonistic analogs of gh-rh inhibiting igf-i and -ii

Publications (1)

Publication Number	Publication Date
UA68407C2 true UA68407C2 (en)	2004-08-16

Family

ID=22737273

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2001064393A UA68407C2 (en)	1998-11-25	1999-11-23	Antagonistic analogues of growth hormone releasing hormone (gh-rh) inhibiting activity of endogenous insulin-like growth factors

Country Status (28)

Country	Link
US (2)	US6057422A (pl)
EP (1)	EP1133522B1 (pl)
JP (1)	JP2002530432A (pl)
KR (1)	KR100629013B1 (pl)
CN (1)	CN100422211C (pl)
AR (1)	AR022392A1 (pl)
AT (1)	ATE332310T1 (pl)
AU (1)	AU757222B2 (pl)
BG (1)	BG65137B1 (pl)
BR (1)	BR9915512A (pl)
CA (1)	CA2351665C (pl)
CO (1)	CO5180565A1 (pl)
CZ (1)	CZ20011794A3 (pl)
DE (1)	DE69932255T2 (pl)
DK (1)	DK1133522T3 (pl)
ES (1)	ES2264279T3 (pl)
HU (1)	HUP0105094A3 (pl)
IL (1)	IL142899A0 (pl)
NO (1)	NO20012489L (pl)
NZ (1)	NZ511307A (pl)
PL (1)	PL197471B1 (pl)
PT (1)	PT1133522E (pl)
RU (1)	RU2235099C2 (pl)
SK (1)	SK7252001A3 (pl)
TR (1)	TR200101492T2 (pl)
TW (1)	TW585873B (pl)
UA (1)	UA68407C2 (pl)
WO (1)	WO2000031136A1 (pl)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2454135A1 (en) *	2001-07-12	2003-01-23	Exelixis, Inc.	Gpcs as modifiers of the irrtk and p21 pathways and methods of use
US20040121407A1 (en) *	2002-09-06	2004-06-24	Elixir Pharmaceuticals, Inc.	Regulation of the growth hormone/IGF-1 axis
KR20050071498A (ko) *	2002-09-18	2005-07-07	상트르 오스피딸리에 드 루니버시떼 드 몬트리알	성장 호르몬 방출 호르몬 유사체
TW200517400A (en) *	2003-08-05	2005-06-01	Univ Tulane	Antagonistic analogs of GH-RH (2003)
CA2718146C (en) *	2008-03-28	2016-09-20	The University Of Miami	Novel n- and c-terminal substituted antagonistic analogs of gh-rh
US8691942B2 (en)	2008-03-28	2014-04-08	University Of Miami	N- and C- terminal substituted antagonistic analogs of GH-RH
CN102083451A (zh)	2008-06-12	2011-06-01	赛恩泰新公司	癌症的抑制
CA2727082C (en)	2008-06-12	2019-02-26	Syntaxin Limited	Fusion proteins for use in suppression of acromegaly
GB0820970D0 (en)	2008-11-17	2008-12-24	Syntaxin Ltd	Suppression of cancer
US8227421B2 (en) *	2009-09-17	2012-07-24	University Of Miami	Fluorinated GHRH antagonists
KR20140027284A (ko)	2011-04-21	2014-03-06	쎄러테크놀로지스 인코포레이티드	성장 호르몬 방출 인자(grf) 유사체 및 이의 용도
US9079974B2 (en) *	2011-12-21	2015-07-14	The University Of Miami	GH-RH analogs with potent agonistic effects
WO2014100816A2 (en)	2012-12-21	2014-06-26	University Of Miami	Ghrh agonists for islet cell transplantation and function and the treatment of diabetes
US9855312B2 (en)	2012-12-21	2018-01-02	University Of Miami	GHRH agonists for the treatment of ischemic disorders
WO2016077620A1 (en)	2014-11-12	2016-05-19	The United States Of America, As Represented By The Secretary, Department Of Health And Human Services	Treatment of hormonal disorders of growth
CA3129405A1 (en)	2019-02-08	2020-08-13	United States Government As Represented By The Department Of Veterans Affairs	Growth hormone-releasing hormone antagonists and uses thereof
CN114126653B (zh)	2019-07-18	2024-02-20	迈阿密大学	用于治疗结节病的方法的ghrh拮抗剂

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4659693A (en) *	1984-04-30	1987-04-21	Syntex (U.S.A.) Inc.	N,N'-dialkyl substituted guanidino amino acyl residue substituted GRF-analog peptides
CA2082059A1 (en) *	1990-05-04	1991-11-05	David H. Coy	Synthetic grf analogs
RU2119800C1 (ru) *	1990-11-14	1998-10-10	Дзе Апджон Компани	Аналог пептида фактора гормона роста (фгр), способ стимулирования секреции гормона роста и композиция для стимулирования секреции
US5550212A (en) *	1993-12-17	1996-08-27	The Administrators Of The Tulane Educational Fund	Analogues of hGH-RH(1-29)NH2 having antagonistic activity
US5942489A (en) *	1996-05-03	1999-08-24	The Administrators Of The Tulane Educational Fund	HGH-RH(1-29)NH2 analogues having antagonistic activity

1998
- 1998-11-25 US US09/199,381 patent/US6057422A/en not_active Expired - Fee Related
1999
- 1999-11-16 CO CO99072002A patent/CO5180565A1/es not_active Application Discontinuation
- 1999-11-23 SK SK725-2001A patent/SK7252001A3/sk unknown
- 1999-11-23 KR KR1020017006568A patent/KR100629013B1/ko not_active Expired - Fee Related
- 1999-11-23 PL PL349877A patent/PL197471B1/pl unknown
- 1999-11-23 AT AT99963962T patent/ATE332310T1/de not_active IP Right Cessation
- 1999-11-23 RU RU2001117218/04A patent/RU2235099C2/ru not_active IP Right Cessation
- 1999-11-23 JP JP2000583962A patent/JP2002530432A/ja not_active Ceased
- 1999-11-23 IL IL14289999A patent/IL142899A0/xx not_active IP Right Cessation
- 1999-11-23 EP EP99963962A patent/EP1133522B1/en not_active Expired - Lifetime
- 1999-11-23 TR TR2001/01492T patent/TR200101492T2/xx unknown
- 1999-11-23 NZ NZ511307A patent/NZ511307A/en unknown
- 1999-11-23 CZ CZ20011794A patent/CZ20011794A3/cs unknown
- 1999-11-23 CA CA002351665A patent/CA2351665C/en not_active Expired - Fee Related
- 1999-11-23 AU AU20291/00A patent/AU757222B2/en not_active Ceased
- 1999-11-23 PT PT99963962T patent/PT1133522E/pt unknown
- 1999-11-23 DE DE69932255T patent/DE69932255T2/de not_active Expired - Fee Related
- 1999-11-23 HU HU0105094A patent/HUP0105094A3/hu unknown
- 1999-11-23 UA UA2001064393A patent/UA68407C2/uk unknown
- 1999-11-23 ES ES99963962T patent/ES2264279T3/es not_active Expired - Lifetime
- 1999-11-23 WO PCT/US1999/027822 patent/WO2000031136A1/en not_active Ceased
- 1999-11-23 DK DK99963962T patent/DK1133522T3/da active
- 1999-11-23 CN CNB998137359A patent/CN100422211C/zh not_active Expired - Fee Related
- 1999-11-23 BR BR9915512-5A patent/BR9915512A/pt not_active Application Discontinuation
- 1999-11-24 AR ARP990105977A patent/AR022392A1/es active IP Right Grant
- 1999-11-24 TW TW088120503A patent/TW585873B/zh not_active IP Right Cessation
2000
- 2000-04-11 US US09/547,215 patent/US7026281B1/en not_active Expired - Fee Related
2001
- 2001-05-21 NO NO20012489A patent/NO20012489L/no not_active Application Discontinuation
- 2001-06-22 BG BG105638A patent/BG65137B1/bg unknown

Also Published As

Publication number	Publication date
CA2351665A1 (en)	2000-06-02
US7026281B1 (en)	2006-04-11
NZ511307A (en)	2005-01-28
CN1328570A (zh)	2001-12-26
PT1133522E (pt)	2006-11-30
PL349877A1 (en)	2002-09-23
BG105638A (en)	2002-01-31
WO2000031136A1 (en)	2000-06-02
IL142899A0 (en)	2002-04-21
CA2351665C (en)	2008-09-02
KR20010101079A (ko)	2001-11-14
TR200101492T2 (tr)	2001-11-21
DE69932255T2 (de)	2007-05-31
WO2000031136A9 (en)	2001-07-19
DE69932255D1 (de)	2006-08-17
RU2235099C2 (ru)	2004-08-27
ATE332310T1 (de)	2006-07-15
TW585873B (en)	2004-05-01
HK1036461A1 (en)	2002-01-04
HUP0105094A3 (en)	2002-05-28
AR022392A1 (es)	2002-09-04
DK1133522T3 (da)	2006-11-06
HUP0105094A2 (hu)	2002-04-29
SK7252001A3 (en)	2002-02-05
NO20012489L (no)	2001-07-04
BR9915512A (pt)	2001-08-07
BG65137B1 (bg)	2007-03-30
CZ20011794A3 (cs)	2002-02-13
US6057422A (en)	2000-05-02
CO5180565A1 (es)	2002-07-30
PL197471B1 (pl)	2008-04-30
NO20012489D0 (no)	2001-05-21
JP2002530432A (ja)	2002-09-17
KR100629013B1 (ko)	2006-09-26
ES2264279T3 (es)	2006-12-16
AU757222B2 (en)	2003-02-06
EP1133522A1 (en)	2001-09-19
CN100422211C (zh)	2008-10-01
AU2029100A (en)	2000-06-13
EP1133522B1 (en)	2006-07-05

Publication	Publication Date	Title
UA68407C2 (en)	2004-08-16	Antagonistic analogues of growth hormone releasing hormone (gh-rh) inhibiting activity of endogenous insulin-like growth factors
RU2233170C2 (ru)	2004-07-27	Композиция контролированного высвобождения, включающая gnrh-ii
CN104395338B (zh)	2019-05-10	人胰岛淀粉样多肽类似物
RU2335506C2 (ru)	2008-10-10	Пептидные аналоги gh-rh с антагонистическим действием, способ снижения уровня gh, способ снижения уровня igf-i и igf-ii, применение для ингибирования роста раковых клеток, фармакологически приемлемая композиция (варианты)
JP2001501585A (ja)	2001-02-06	拮抗活性を有するｈＧＨ―ＲＨ（１―２９）ＮＨ▲下２▼類似体
CN101983068B (zh)	2014-12-24	N末端和c末端取代的人gh-rh拮抗类似物
EP0734396B1 (en)	2000-11-08	ANALOGUES OF hGH-RH (1-29)NH2 HAVING ANTAGONISTIC ACTIVITY
US7189692B2 (en)	2007-03-13	Synthetic peptides and pseudopeptides having osteogenic activity and pharmaceutical compositions containing the same
DK171682B1 (da)	1997-03-10	Væksthormon-frigørende peptid og pharmaceutisk acceptable salte deraf, sammensætning med indhold deraf samt fremgangsmåde til fremstilling af peptider
EP2198878A1 (en)	2010-06-23	Polypeptide bombesin antagonists
EP0541654A1 (en)	1993-05-19	Bombesin antagonists
JP2001335596A (ja)	2001-12-04	新規ペプチド及びその医薬用途
NZ226764A (en)	1992-03-26	Peptides containing a succinimide residue and having hypoglycamic activity
JP2001098000A (ja)	2001-04-10	新規ペプチド及びその医薬用途
HK1036461B (en)	2006-09-15	Antagonistic analogs of gh-rh inhibiting igf-i and -ii