UA76949C2 - Kahalalide compounds - Google Patents
Kahalalide compounds Download PDFInfo
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- UA76949C2 UA76949C2 UA2002097267A UA2002097267A UA76949C2 UA 76949 C2 UA76949 C2 UA 76949C2 UA 2002097267 A UA2002097267 A UA 2002097267A UA 2002097267 A UA2002097267 A UA 2002097267A UA 76949 C2 UA76949 C2 UA 76949C2
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 85
- 229930194861 kahalalide Natural products 0.000 title abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 67
- 150000001413 amino acids Chemical class 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- -1 amino, carboxyl Chemical group 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 238000007363 ring formation reaction Methods 0.000 claims description 17
- 125000002252 acyl group Chemical group 0.000 claims description 16
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- NNBDGOASYKFATB-JJVHZCDQSA-N (6r,9r,16s,22s)-16-(1h-indol-3-ylmethyl)-6,9-dimethyl-13-(6-methylheptyl)-3,19-bis(2-methylpropyl)-14-oxa-1,4,7,10,17,20-hexazabicyclo[20.3.0]pentacosane-2,5,8,11,15,18,21-heptone Chemical class O=C1OC(CCCCCC(C)C)CC(=O)N[C@H](C)C(=O)N[C@H](C)C(=O)NC(CC(C)C)C(=O)N2CCC[C@H]2C(=O)NC(CC(C)C)C(=O)N[C@H]1CC1=CNC2=CC=CC=C12 NNBDGOASYKFATB-JJVHZCDQSA-N 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 125000002723 alicyclic group Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- XRQYTURCNQEJNM-UHFFFAOYSA-N kahalalide E Natural products CC(C)CCCCCC1CC(=O)NC(C)C(=O)CC(C)C(=O)NC(CC(C)C)C(=O)N2CCCC2C(=O)NC(CC(C)C)C(=O)NC(Cc3c[nH]c4ccccc34)C(=O)N1 XRQYTURCNQEJNM-UHFFFAOYSA-N 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000005518 carboxamido group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 235000010469 Glycine max Nutrition 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 2
- 244000068988 Glycine max Species 0.000 claims 1
- 241001436793 Meru Species 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 7
- 230000004071 biological effect Effects 0.000 abstract description 3
- 230000003278 mimic effect Effects 0.000 abstract description 2
- RCGXNDQKCXNWLO-WLEIXIPESA-N (2r)-n-[(2s)-5-amino-1-[[(2r,3r)-1-[[(3s,6z,9s,12r,15r,18r,19s)-9-benzyl-15-[(2r)-butan-2-yl]-6-ethylidene-19-methyl-2,5,8,11,14,17-hexaoxo-3,12-di(propan-2-yl)-1-oxa-4,7,10,13,16-pentazacyclononadec-18-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopent Chemical compound N([C@@H](CCCN)C(=O)N[C@H]([C@H](C)CC)C(=O)N[C@H]1C(N[C@@H](C(=O)N[C@@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)NC(/C(=O)N[C@H](C(=O)O[C@H]1C)C(C)C)=C\C)C(C)C)[C@H](C)CC)=O)C(=O)[C@H]1CCCN1C(=O)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](NC(=O)CCCC(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C RCGXNDQKCXNWLO-WLEIXIPESA-N 0.000 abstract 1
- 108010091711 kahalalide F Proteins 0.000 abstract 1
- 229920005989 resin Polymers 0.000 description 74
- 239000011347 resin Substances 0.000 description 74
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 61
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- 235000001014 amino acid Nutrition 0.000 description 51
- 238000002474 experimental method Methods 0.000 description 31
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- 238000005859 coupling reaction Methods 0.000 description 18
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 14
- 125000001151 peptidyl group Chemical group 0.000 description 14
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- 238000012986 modification Methods 0.000 description 6
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 6
- 239000007790 solid phase Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 235000014393 valine Nutrition 0.000 description 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 5
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
- 241001446467 Mama Species 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 5
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- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 5
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- 125000000962 organic group Chemical group 0.000 description 5
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
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- CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 4
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- 125000003277 amino group Chemical group 0.000 description 3
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
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- NEPVMCVSNSCONF-UCWDGQLDSA-N (4r)-5-[[1-[[1-[[1-[(2r)-2-[[(2s)-5-amino-1-[[(2r,3s)-1-[[(6z,9s,18r,19r)-9-benzyl-6-ethylidene-19-methyl-2,5,8,11,14,17-hexaoxo-3,12,15-tri(propan-2-yl)-1-oxa-4,7,10,13,16-pentazacyclononadec-18-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl Chemical compound N([C@@H](CCCN)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]1C(NC(C(=O)NC(C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)NC(/C(=O)NC(C(=O)O[C@@H]1C)C(C)C)=C\C)C(C)C)C(C)C)=O)C(=O)[C@H]1CCCN1C(=O)C(NC(=O)C(NC(=O)C(NC(=O)[C@@H](CCC(O)=O)NC(=O)CCCCCC(C)C)C(C)C)C(C)C)C(C)C NEPVMCVSNSCONF-UCWDGQLDSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K11/00—Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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- 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
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
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- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Detergent Compositions (AREA)
- Silver Salt Photography Or Processing Solution Therefor (AREA)
- Optical Record Carriers And Manufacture Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
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| GBGB0002952.0A GB0002952D0 (en) | 2000-02-09 | 2000-02-09 | Process for producing kahalalide F compounds |
| PCT/GB2001/000576 WO2001058934A2 (en) | 2000-02-09 | 2001-02-09 | Kahalalide f and related compounds |
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| UA76949C2 true UA76949C2 (en) | 2006-10-16 |
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| US20050054555A1 (en) * | 2001-10-19 | 2005-03-10 | Jose Jimeno | Kahalalide compounds for use in cancer therapy |
| GB0304367D0 (en) * | 2003-02-26 | 2003-04-02 | Pharma Mar Sau | Methods for treating psoriasis |
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| CN100396696C (zh) * | 2004-04-23 | 2008-06-25 | 中国科学院海洋研究所 | 一种海洋绿藻在提取抗肿瘤活性环肽组分中的应用 |
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| EP2252315A1 (en) * | 2008-01-30 | 2010-11-24 | Pharma Mar, S.A. | Improved antitumoral treatments |
| JP2011513370A (ja) * | 2008-03-07 | 2011-04-28 | ファルマ・マール・ソシエダード・アノニマ | 改善された抗腫瘍治療法 |
| CN103641891B (zh) * | 2013-05-23 | 2017-03-22 | 深圳翰宇药业股份有限公司 | 一种制备Kahalalide F的方法 |
| CA2999367C (en) | 2015-09-23 | 2023-09-26 | Xw Laboratories Inc. | Prodrugs of gamma-hydroxybutyric acid, compositions and uses thereof |
| KR102510784B1 (ko) | 2017-03-30 | 2023-03-15 | 엑스더블유파마 리미티드 | 이환형 헤테로아릴 유도체 및 이의 제조 및 용도 |
| JOP20190254A1 (ar) | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | مركبات مضادة للأورام |
| WO2020062251A1 (en) | 2018-09-30 | 2020-04-02 | Xw Laboratories, Inc. | Compounds as neuronal histamine receptor-3 antagonists and uses thereof |
| WO2021127461A1 (en) | 2019-12-20 | 2021-06-24 | Xw Laboratories Limited | Methods of synthesizing 4-valyloxybutyric acid |
| WO2021257886A1 (en) | 2020-06-18 | 2021-12-23 | XWPharma Ltd. | Controlled release granulations of water-soluble active pharmaceutical ingredients |
| WO2021257832A1 (en) | 2020-06-18 | 2021-12-23 | XWPharma Ltd. | Pharmaceutical granulations of water-soluble active pharmaceutical ingredients |
| CN116261451A (zh) | 2020-07-24 | 2023-06-13 | 凯瑞康宁生物工程有限公司 | γ-羟基丁酸衍生物的药物组合物和药物动力学 |
| CN119970650A (zh) | 2020-10-05 | 2025-05-13 | 凯瑞康宁生物工程有限公司 | γ-羟基丁酸衍生物的修饰释放组合物 |
| EP4308086B1 (en) | 2021-03-19 | 2025-10-15 | XWPharma Ltd. | Pharmacokinetics of combined release formulations of a gamma-hydroxybutyric acid derivative |
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| GR870129B (en) * | 1987-01-27 | 1987-02-04 | Giatzidis Ippokratis | Stable bicarbonate - glycylglycine dialysate for hemodialysis and peritoneal dialysis |
| US5399363A (en) * | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
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2000
- 2000-02-09 GB GBGB0002952.0A patent/GB0002952D0/en not_active Ceased
-
2001
- 2001-02-09 SK SK1124-2002A patent/SK11242002A3/sk not_active Application Discontinuation
- 2001-02-09 ES ES01904169T patent/ES2292558T3/es not_active Expired - Lifetime
- 2001-02-09 EP EP10178150A patent/EP2258715A1/en not_active Withdrawn
- 2001-02-09 DE DE60130192T patent/DE60130192T2/de not_active Expired - Lifetime
- 2001-02-09 NZ NZ520488A patent/NZ520488A/en not_active IP Right Cessation
- 2001-02-09 AT AT01904169T patent/ATE371667T1/de active
- 2001-02-09 CN CN200810178807.9A patent/CN101597326B/zh not_active Expired - Fee Related
- 2001-02-09 MX MXPA02007760A patent/MXPA02007760A/es active IP Right Grant
- 2001-02-09 EP EP07010878A patent/EP1829889A3/en not_active Withdrawn
- 2001-02-09 KR KR1020027010355A patent/KR100871489B1/ko not_active Expired - Fee Related
- 2001-02-09 RU RU2002123877/04A patent/RU2280039C2/ru active
- 2001-02-09 PL PL356800A patent/PL207121B1/pl unknown
- 2001-02-09 US US10/182,881 patent/US7482429B2/en not_active Expired - Fee Related
- 2001-02-09 CA CA2399187A patent/CA2399187C/en not_active Expired - Fee Related
- 2001-02-09 DK DK01904169T patent/DK1254162T3/da active
- 2001-02-09 AU AU32086/01A patent/AU783542B2/en not_active Ceased
- 2001-02-09 HU HU0301817A patent/HUP0301817A3/hu unknown
- 2001-02-09 BR BR0108213-2A patent/BR0108213A/pt not_active IP Right Cessation
- 2001-02-09 JP JP2001558081A patent/JP5188665B2/ja not_active Expired - Fee Related
- 2001-02-09 CZ CZ2002-2740A patent/CZ304258B6/cs not_active IP Right Cessation
- 2001-02-09 CN CN01807743A patent/CN1422278A/zh active Pending
- 2001-02-09 EP EP01904169A patent/EP1254162B1/en not_active Expired - Lifetime
- 2001-02-09 IL IL15098101A patent/IL150981A0/xx unknown
- 2001-02-09 WO PCT/GB2001/000576 patent/WO2001058934A2/en not_active Ceased
- 2001-02-09 PT PT01904169T patent/PT1254162E/pt unknown
- 2001-09-02 UA UA2002097267A patent/UA76949C2/uk unknown
-
2002
- 2002-07-30 IL IL150981A patent/IL150981A/en not_active IP Right Cessation
- 2002-08-08 NO NO20023749A patent/NO331847B1/no not_active IP Right Cessation
- 2002-08-21 BG BG107020A patent/BG65926B1/bg unknown
-
2007
- 2007-11-08 CY CY20071101442T patent/CY1106992T1/el unknown
-
2008
- 2008-08-25 US US12/198,013 patent/US20080318849A1/en not_active Abandoned
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