ZA200301720B - Substituted dipeptides as growth hormone secretagogues. - Google Patents

Substituted dipeptides as growth hormone secretagogues. Download PDF

Info

Publication number: ZA200301720B
Authority: ZA; South Africa
Prior art keywords: aryl; amino; compound; dioxo; ylmethyl
Prior art date: 2000-10-13

Application number

ZA200301720A

Other languages

English (en)

Inventor

Jeffrey Alan Dodge

Louis Nickolaus Jungheim

Gerd Ruehter

Britta Evers

Brian Stephen Muehl

Kenneth Jeff Thrasher

Original Assignee

Lilly Co Eli

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.)

2000-10-13

Filing date

2003-02-28

Publication date

2004-06-21

2003-02-28 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

2004-06-21 Publication of ZA200301720B publication Critical patent/ZA200301720B/en

Links

239000003324 growth hormone secretagogue Substances 0.000 title claims description 5
108010016626 Dipeptides Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 110
-1 substituted Chemical class 0.000 claims description 106
125000000217 alkyl group Chemical group 0.000 claims description 63
229910052739 hydrogen Inorganic materials 0.000 claims description 57
239000001257 hydrogen Substances 0.000 claims description 57
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 57
125000003118 aryl group Chemical group 0.000 claims description 45
239000000122 growth hormone Substances 0.000 claims description 29
102000018997 Growth Hormone Human genes 0.000 claims description 28
108010051696 Growth Hormone Proteins 0.000 claims description 28
229910052799 carbon Inorganic materials 0.000 claims description 23
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 20
125000004432 carbon atom Chemical group C* 0.000 claims description 20
238000000034 method Methods 0.000 claims description 17
125000000753 cycloalkyl group Chemical group 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
239000000203 mixture Substances 0.000 claims description 15
125000001041 indolyl group Chemical group 0.000 claims description 14
150000001408 amides Chemical class 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 11
125000003107 substituted aryl group Chemical group 0.000 claims description 11
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 10
125000006239 protecting group Chemical group 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
241001465754 Metazoa Species 0.000 claims description 7
125000002837 carbocyclic group Chemical group 0.000 claims description 7
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
239000012453 solvate Substances 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
125000004429 atom Chemical group 0.000 claims description 6
239000003795 chemical substances by application Substances 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 5
239000002253 acid Substances 0.000 claims description 5
230000008878 coupling Effects 0.000 claims description 5
238000010168 coupling process Methods 0.000 claims description 5
238000005859 coupling reaction Methods 0.000 claims description 5
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 5
125000001624 naphthyl group Chemical group 0.000 claims description 5
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 4
238000009472 formulation Methods 0.000 claims description 4
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
230000004962 physiological condition Effects 0.000 claims description 3
NTYQZLYVUKIFLI-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]-n-methylmethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNC)=C1C1=CC=C(Cl)C=C1 NTYQZLYVUKIFLI-UHFFFAOYSA-N 0.000 claims description 2
102100033367 Appetite-regulating hormone Human genes 0.000 claims description 2
101710111255 Appetite-regulating hormone Proteins 0.000 claims description 2
125000002877 alkyl aryl group Chemical group 0.000 claims description 2
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
USFSDJYPLHJUMP-UHFFFAOYSA-N n-[[3-(4-tert-butylphenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]methyl]ethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNCC)=C1C1=CC=C(C(C)(C)C)C=C1 USFSDJYPLHJUMP-UHFFFAOYSA-N 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 10
125000003342 alkenyl group Chemical group 0.000 claims 3
YWAVZUWLSRORPG-UHFFFAOYSA-N 2-[(2-amino-2-methylpropanoyl)amino]-5-phenylpentanoic acid Chemical compound CC(C)(N)C(=O)NC(C(O)=O)CCCC1=CC=CC=C1 YWAVZUWLSRORPG-UHFFFAOYSA-N 0.000 claims 2
239000003814 drug Substances 0.000 claims 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
TYQGMABQHZEQFO-UHFFFAOYSA-N n-[[3-(4-fluorophenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]methyl]ethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNCC)=C1C1=CC=C(F)C=C1 TYQGMABQHZEQFO-UHFFFAOYSA-N 0.000 claims 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
GMKYVKWGXBQAMB-UHFFFAOYSA-N n-[[3-(4-chlorophenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]methyl]ethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNCC)=C1C1=CC=C(Cl)C=C1 GMKYVKWGXBQAMB-UHFFFAOYSA-N 0.000 claims 1
YDJFLLMIMLKRPD-UHFFFAOYSA-N n-[[3-(4-methylphenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]methyl]ethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNCC)=C1C1=CC=C(C)C=C1 YDJFLLMIMLKRPD-UHFFFAOYSA-N 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
102100022831 Somatoliberin Human genes 0.000 description 20
101710142969 Somatoliberin Proteins 0.000 description 19
125000005843 halogen group Chemical group 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 12
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 8
239000000543 intermediate Substances 0.000 description 7
239000007858 starting material Substances 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
235000001014 amino acid Nutrition 0.000 description 6
150000001413 amino acids Chemical class 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
125000005842 heteroatom Chemical group 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
230000000694 effects Effects 0.000 description 5
230000028327 secretion Effects 0.000 description 5
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
230000003213 activating effect Effects 0.000 description 4
125000001246 bromo group Chemical group Br* 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
125000004356 hydroxy functional group Chemical group O* 0.000 description 4
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
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YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
230000006181 N-acylation Effects 0.000 description 3
239000012317 TBTU Substances 0.000 description 3
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
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238000001727 in vivo Methods 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
125000001151 peptidyl group Chemical group 0.000 description 3
239000003488 releasing hormone Substances 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
230000009469 supplementation Effects 0.000 description 3
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
102000002265 Human Growth Hormone Human genes 0.000 description 2
108010000521 Human Growth Hormone Proteins 0.000 description 2
239000000854 Human Growth Hormone Substances 0.000 description 2
206010062767 Hypophysitis Diseases 0.000 description 2
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
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MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
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125000001931 aliphatic group Chemical group 0.000 description 2
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150000003857 carboxamides Chemical class 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
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238000000434 field desorption mass spectrometry Methods 0.000 description 2
125000001072 heteroaryl group Chemical group 0.000 description 2
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NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
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DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
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 2
YFGBQHOOROIVKG-BHDDXSALSA-N (2R)-2-[[(2R)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H](C(=O)N[C@H](CCSC)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 YFGBQHOOROIVKG-BHDDXSALSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

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Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

ZA200301720A 2000-10-13 2003-02-28 Substituted dipeptides as growth hormone secretagogues. ZA200301720B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US24045600P	2000-10-13	2000-10-13

Publications (1)

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ZA200301720B true ZA200301720B (en)	2004-06-21

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EP (1)	EP1326851B1 (cs)
JP (1)	JP2004511552A (cs)
KR (1)	KR20030042014A (cs)
CN (1)	CN1469871A (cs)
AT (1)	ATE270280T1 (cs)
AU (2)	AU1121902A (cs)
BR (1)	BR0114630A (cs)
CA (1)	CA2419388A1 (cs)
CZ (1)	CZ20031029A3 (cs)
DE (1)	DE60104141T2 (cs)
DZ (1)	DZ3482A1 (cs)
EA (1)	EA006102B1 (cs)
EC (1)	ECSP034551A (cs)
ES (1)	ES2223926T3 (cs)
HR (1)	HRP20030288B1 (cs)
HU (1)	HUP0301351A3 (cs)
IL (1)	IL154809A0 (cs)
MX (1)	MXPA03003217A (cs)
NO (1)	NO20031687L (cs)
NZ (1)	NZ524232A (cs)
PL (1)	PL361675A1 (cs)
PT (1)	PT1326851E (cs)
SK (1)	SK4182003A3 (cs)
TR (1)	TR200402046T4 (cs)
WO (1)	WO2002032888A1 (cs)
ZA (1)	ZA200301720B (cs)

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WO2007024004A1 (ja)	2005-08-24	2007-03-01	Banyu Pharmaceutical Co., Ltd.	フェニルピリドン誘導体
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JPWO2009110510A1 (ja)	2008-03-06	2011-07-14	Ｍｓｄ株式会社	アルキルアミノピリジン誘導体
US20110015198A1 (en)	2008-03-28	2011-01-20	Banyu Pharmaceutical Co., Inc.	Diarylmethylamide derivative having melanin-concentrating hormone receptor antagonism
EP2810951B1 (en)	2008-06-04	2017-03-15	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
JPWO2009154132A1 (ja)	2008-06-19	2011-12-01	Ｍｓｄ株式会社	スピロジアミン−ジアリールケトオキシム誘導体
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JPWO2010013595A1 (ja)	2008-07-30	2012-01-12	Ｍｓｄ株式会社	５員−５員又は５員−６員縮環シクロアルキルアミン誘導体
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2001
- 2001-10-09 HU HU0301351A patent/HUP0301351A3/hu unknown
- 2001-10-09 CN CNA018172822A patent/CN1469871A/zh active Pending
- 2001-10-09 EA EA200300462A patent/EA006102B1/ru not_active IP Right Cessation
- 2001-10-09 SK SK418-2003A patent/SK4182003A3/sk unknown
- 2001-10-09 MX MXPA03003217A patent/MXPA03003217A/es unknown
- 2001-10-09 CA CA002419388A patent/CA2419388A1/en not_active Abandoned
- 2001-10-09 IL IL15480901A patent/IL154809A0/xx unknown
- 2001-10-09 HR HR20030288A patent/HRP20030288B1/xx not_active IP Right Cessation
- 2001-10-09 TR TR2004/02046T patent/TR200402046T4/xx unknown
- 2001-10-09 PT PT01979233T patent/PT1326851E/pt unknown
- 2001-10-09 AT AT01979233T patent/ATE270280T1/de not_active IP Right Cessation
- 2001-10-09 WO PCT/US2001/027756 patent/WO2002032888A1/en not_active Ceased
- 2001-10-09 CZ CZ20031029A patent/CZ20031029A3/cs unknown
- 2001-10-09 ES ES01979233T patent/ES2223926T3/es not_active Expired - Lifetime
- 2001-10-09 NZ NZ524232A patent/NZ524232A/en unknown
- 2001-10-09 AU AU1121902A patent/AU1121902A/xx active Pending
- 2001-10-09 PL PL01361675A patent/PL361675A1/xx not_active Application Discontinuation
- 2001-10-09 DE DE60104141T patent/DE60104141T2/de not_active Expired - Lifetime
- 2001-10-09 EP EP01979233A patent/EP1326851B1/en not_active Expired - Lifetime
- 2001-10-09 KR KR10-2003-7005203A patent/KR20030042014A/ko not_active Withdrawn
- 2001-10-09 JP JP2002536270A patent/JP2004511552A/ja active Pending
- 2001-10-09 BR BR0114630-0A patent/BR0114630A/pt not_active IP Right Cessation
- 2001-10-09 DZ DZ013482A patent/DZ3482A1/fr active
- 2001-10-09 AU AU2002211219A patent/AU2002211219B2/en not_active Ceased
2003
- 2003-02-28 ZA ZA200301720A patent/ZA200301720B/en unknown
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- 2003-04-11 NO NO20031687A patent/NO20031687L/no unknown

Also Published As

Publication number	Publication date
EA200300462A1 (ru)	2003-08-28
CA2419388A1 (en)	2002-04-25
HK1058194A1 (en)	2004-05-07
HRP20030288B1 (en)	2005-02-28
HUP0301351A3 (en)	2007-05-29
KR20030042014A (ko)	2003-05-27
MXPA03003217A (es)	2003-06-06
AU2002211219B2 (en)	2006-09-14
HRP20030288A2 (en)	2004-02-29
IL154809A0 (en)	2003-10-31
ES2223926T3 (es)	2005-03-01
NZ524232A (en)	2005-01-28
ATE270280T1 (de)	2004-07-15
SK4182003A3 (en)	2004-01-08
TR200402046T4 (tr)	2004-10-21
WO2002032888A1 (en)	2002-04-25
EP1326851B1 (en)	2004-06-30
PL361675A1 (en)	2004-10-04
CN1469871A (zh)	2004-01-21
DE60104141D1 (de)	2004-08-05
DE60104141T2 (de)	2005-06-30
NO20031687L (no)	2003-05-08
EA006102B1 (ru)	2005-08-25
ECSP034551A (es)	2003-05-26
BR0114630A (pt)	2003-07-01
AU1121902A (en)	2002-04-29
PT1326851E (pt)	2004-11-30
JP2004511552A (ja)	2004-04-15
CZ20031029A3 (cs)	2003-09-17
EP1326851A1 (en)	2003-07-16
DZ3482A1 (fr)	2002-04-25
NO20031687D0 (no)	2003-04-11
HUP0301351A2 (hu)	2003-11-28

Publication	Publication Date	Title
EP1326851B1 (en)	2004-06-30	Substituted dipeptides as growth hormone secretagogues
AU2002211219A1 (en)	2002-07-04	Substituted dipeptides as growth hormone secretagogues
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EP1153034B1 (en)	2007-10-17	Growth hormone secretagogues
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IE921321A1 (en)	1992-11-04	Ó-substituted polypeptides having therapeutic activity
EP1497317B1 (en)	2006-09-06	Dipeptidic growth hormone secretagogues
US6828331B1 (en)	2004-12-07	Growth hormone secretagogues
US7125840B2 (en)	2006-10-24	Substituted dipeptides as growth hormone secretagogues
HK1058194B (en)	2005-04-22	Substituted dipeptides as growth hormone secretagogues
US20060167268A1 (en)	2006-07-27	Growth hormone secretagogues
JPH01316399A (ja)	1989-12-21	ポリペプチド