CA2462200A1 - Peptidomimetics of biologically active metallopeptides - Google Patents
Peptidomimetics of biologically active metallopeptides Download PDFInfo
- Publication number
- CA2462200A1 CA2462200A1 CA002462200A CA2462200A CA2462200A1 CA 2462200 A1 CA2462200 A1 CA 2462200A1 CA 002462200 A CA002462200 A CA 002462200A CA 2462200 A CA2462200 A CA 2462200A CA 2462200 A1 CA2462200 A1 CA 2462200A1
- Authority
- CA
- Canada
- Prior art keywords
- amino acid
- peptidomimetic
- phe
- metallopeptide
- biologically active
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000816 peptidomimetic Substances 0.000 title claims abstract description 160
- 238000000034 method Methods 0.000 claims abstract description 497
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 130
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 95
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 53
- 102000004378 Melanocortin Receptors Human genes 0.000 claims abstract description 34
- 108090000950 Melanocortin Receptors Proteins 0.000 claims abstract description 34
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims description 477
- 229910021645 metal ion Inorganic materials 0.000 claims description 103
- 235000001014 amino acid Nutrition 0.000 claims description 81
- 239000000556 agonist Substances 0.000 claims description 80
- 150000001413 amino acids Chemical group 0.000 claims description 73
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 68
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 62
- 239000005557 antagonist Substances 0.000 claims description 60
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 claims description 55
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- 102000005962 receptors Human genes 0.000 claims description 49
- 108020003175 receptors Proteins 0.000 claims description 49
- 230000027455 binding Effects 0.000 claims description 48
- 229910052717 sulfur Inorganic materials 0.000 claims description 42
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- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 239000003446 ligand Substances 0.000 claims description 14
- 150000002500 ions Chemical group 0.000 claims description 12
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- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
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- 229910052720 vanadium Inorganic materials 0.000 claims description 5
- HTIRACJYHNKUDG-QMMMGPOBSA-N (2s)-2-amino-3-(3-sulfanylphenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(S)=C1 HTIRACJYHNKUDG-QMMMGPOBSA-N 0.000 claims description 4
- ONOURAAVVKGJNM-SCZZXKLOSA-N (2s,3r)-2-azaniumyl-3-phenylmethoxybutanoate Chemical compound [O-]C(=O)[C@@H]([NH3+])[C@@H](C)OCC1=CC=CC=C1 ONOURAAVVKGJNM-SCZZXKLOSA-N 0.000 claims description 4
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 claims description 4
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 claims description 4
- UQBOJOOOTLPNST-UHFFFAOYSA-N Dehydroalanine Chemical group NC(=C)C(O)=O UQBOJOOOTLPNST-UHFFFAOYSA-N 0.000 claims description 4
- 108050001049 Extracellular proteins Proteins 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 4
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- 230000007935 neutral effect Effects 0.000 claims description 4
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- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 108020001580 protein domains Proteins 0.000 claims description 4
- 239000003053 toxin Substances 0.000 claims description 4
- 231100000765 toxin Toxicity 0.000 claims description 4
- CKGCFBNYQJDIGS-LBPRGKRZSA-N (2s)-2-azaniumyl-6-(phenylmethoxycarbonylamino)hexanoate Chemical compound [O-]C(=O)[C@@H]([NH3+])CCCCNC(=O)OCC1=CC=CC=C1 CKGCFBNYQJDIGS-LBPRGKRZSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 claims description 3
- 229930195710 D‐cysteine Natural products 0.000 claims description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 3
- 238000003780 insertion Methods 0.000 claims description 3
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- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- OGNKZWAQLJPNLL-STQMWFEESA-N Phe(4-NO2)-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)C)CC1=CC=C([N+]([O-])=O)C=C1 OGNKZWAQLJPNLL-STQMWFEESA-N 0.000 claims 3
- 229910052716 thallium Inorganic materials 0.000 claims 2
- 238000010647 peptide synthesis reaction Methods 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 3
- 238000012360 testing method Methods 0.000 description 184
- 230000006957 competitive inhibition Effects 0.000 description 175
- 230000005764 inhibitory process Effects 0.000 description 175
- WHNFPRLDDSXQCL-UHFFFAOYSA-N α-melanotropin Chemical compound C=1N=CNC=1CC(C(=O)NC(CC=1C=CC=CC=1)C(=O)NC(CCCNC(N)=N)C(=O)NC(CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)NC(CCCCN)C(=O)N1C(CCC1)C(=O)NC(C(C)C)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CO)NC(=O)C(NC(=O)C(CO)NC(C)=O)CC1=CC=C(O)C=C1 WHNFPRLDDSXQCL-UHFFFAOYSA-N 0.000 description 174
- 238000007429 general method Methods 0.000 description 172
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 120
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- 238000005481 NMR spectroscopy Methods 0.000 description 75
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 69
- 229940024606 amino acid Drugs 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 53
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
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Classifications
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
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- C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/021—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
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- C07—ORGANIC CHEMISTRY
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
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- 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
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- C07K5/0823—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp and Pro-amino acid; Derivatives thereof
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- C07—ORGANIC CHEMISTRY
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- 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
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- 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
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- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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- 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
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- G16B15/00—ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
- G16B15/30—Drug targeting using structural data; Docking or binding prediction
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US31140401P | 2001-08-10 | 2001-08-10 | |
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PCT/US2002/025574 WO2003013571A1 (en) | 2001-08-10 | 2002-08-12 | Peptidomimetics of biologically active metallopeptides |
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CA2462200A1 true CA2462200A1 (en) | 2003-02-20 |
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CA002462200A Abandoned CA2462200A1 (en) | 2001-08-10 | 2002-08-12 | Peptidomimetics of biologically active metallopeptides |
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US7718802B2 (en) | 2001-08-10 | 2010-05-18 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
AU2002331064B2 (en) * | 2001-08-10 | 2007-08-23 | Palatin Technologies, Inc. | Peptidomimetics of biologically active metallopeptides |
US7732451B2 (en) * | 2001-08-10 | 2010-06-08 | Palatin Technologies, Inc. | Naphthalene-containing melanocortin receptor-specific small molecule |
US7456184B2 (en) * | 2003-05-01 | 2008-11-25 | Palatin Technologies Inc. | Melanocortin receptor-specific compounds |
US7655658B2 (en) * | 2001-08-10 | 2010-02-02 | Palatin Technologies, Inc. | Thieno [2,3-D]pyrimidine-2,4-dione melanocortin-specific compounds |
EP1469875A1 (en) * | 2002-01-29 | 2004-10-27 | Wyeth | Compositions and methods for modulating connexin hemichannels |
US7026335B2 (en) | 2002-04-30 | 2006-04-11 | The Procter & Gamble Co. | Melanocortin receptor ligands |
US7132539B2 (en) | 2002-10-23 | 2006-11-07 | The Procter & Gamble Company | Melanocortin receptor ligands |
US7727990B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine and keto-piperazine compounds |
US7727991B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific single acyl piperazine compounds |
US7968548B2 (en) * | 2003-05-01 | 2011-06-28 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine compounds with diamine groups |
WO2005102340A1 (en) * | 2003-05-30 | 2005-11-03 | Palatin Technologies, Inc. | Piperazine melanocortin-specific compounds |
WO2005079574A1 (en) * | 2004-01-21 | 2005-09-01 | Palatin Technologies, Inc. | Bicyclic melanocorin-specific compounds |
US7709484B1 (en) | 2004-04-19 | 2010-05-04 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
EP1688161A1 (en) * | 2004-11-02 | 2006-08-09 | Switch Biotech Aktiengesellschaft | Use of pirlindole for the treatment of diseases which are characterized by proliferation of t-lymphocytes and/or hyperproliferation of keratinocytes in particular atopic dermatitis and psoriasis |
ATE460159T1 (de) | 2005-01-26 | 2010-03-15 | Allergan Inc | Verwendung von 1- benzyl-1- hydroxy-2, 3-diamino- propylaminen, 3-benzyl-3 hydroxy-2-amino- propionsäureamiden und verwandten verbindungen als analgetika |
US20070129444A1 (en) * | 2005-12-06 | 2007-06-07 | Mallinckrodt Inc. | Novel weight reduction composition and uses thereof |
SG170767A1 (en) | 2005-12-23 | 2011-05-30 | Zealand Pharma As | Modified lysine-mimetic compounds |
KR101069051B1 (ko) | 2006-05-23 | 2011-09-29 | 아이알엠 엘엘씨 | 채널 활성화 프로테아제 억제제로서의 화합물 및 조성물 |
AU2007283113A1 (en) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, processes for preparing them, medicaments comprising these compounds, and their use |
US7834017B2 (en) | 2006-08-11 | 2010-11-16 | Palatin Technologies, Inc. | Diamine-containing, tetra-substituted piperazine compounds having identical 1- and 4-substituents |
PT2104535E (pt) * | 2007-01-10 | 2011-03-31 | Irm Llc | Compostos e composições como inibidores da protease de activação de canal |
WO2008090357A2 (en) * | 2007-01-24 | 2008-07-31 | Palatin Technologies, Inc. | N, n; -substituted piperazines binding to melanocortin receptor |
WO2008128171A2 (en) * | 2007-04-13 | 2008-10-23 | The Regents Of The University Of Michigan | Diazo bicyclic smac mimetics and the uses thereof |
US20090081197A1 (en) * | 2007-06-01 | 2009-03-26 | Palatin Technologies, Inc. | Methods for Selection of Melanocortin Receptor-Specific Agents for Treatment of Obesity |
US20090076029A1 (en) * | 2007-06-01 | 2009-03-19 | Palatin Technologies, Inc. | Compounds and Methods for Treating Obesity |
EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
EP2242745A1 (de) * | 2008-02-07 | 2010-10-27 | Sanofi-Aventis | Neue phenyl-substituierte imidazolidine, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
EP2257533B1 (en) * | 2008-02-29 | 2013-09-18 | Mimetica Pty Limited | 3-substituted-1,4-diazepan-2-one melanocortin-5 receptor antagonists |
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JP5265762B2 (ja) | 2008-05-13 | 2013-08-14 | ユニバーシティ・オブ・カンザス | 金属抽出ペプチド(map)タグおよび関連する方法 |
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-
2002
- 2002-08-12 AU AU2002331064A patent/AU2002331064B2/en not_active Ceased
- 2002-08-12 WO PCT/US2002/025574 patent/WO2003013571A1/en active Application Filing
- 2002-08-12 JP JP2003518577A patent/JP2005504043A/ja active Pending
- 2002-08-12 EP EP02768507A patent/EP1425029A4/en not_active Withdrawn
- 2002-08-12 CA CA002462200A patent/CA2462200A1/en not_active Abandoned
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2004
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- 2004-02-10 US US10/776,419 patent/US7807678B2/en not_active Expired - Fee Related
- 2004-02-10 US US10/776,657 patent/US7189755B2/en not_active Expired - Fee Related
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2007
- 2007-03-01 US US11/680,932 patent/US7601753B2/en not_active Expired - Fee Related
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EP1425029A4 (en) | 2006-06-07 |
US20040152134A1 (en) | 2004-08-05 |
US7601753B2 (en) | 2009-10-13 |
JP2005504043A (ja) | 2005-02-10 |
US20070155670A1 (en) | 2007-07-05 |
AU2002331064B2 (en) | 2007-08-23 |
US20040171520A1 (en) | 2004-09-02 |
US7807678B2 (en) | 2010-10-05 |
WO2003013571A1 (en) | 2003-02-20 |
US20040167201A1 (en) | 2004-08-26 |
US7189755B2 (en) | 2007-03-13 |
EP1425029A1 (en) | 2004-06-09 |
US7326707B2 (en) | 2008-02-05 |
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