CZ304258B6 - Kahalalidová sloučenina, způsob její přípravy, farmaceutický prostředek ji obsahující a její použití - Google Patents
Kahalalidová sloučenina, způsob její přípravy, farmaceutický prostředek ji obsahující a její použití Download PDFInfo
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- CZ304258B6 CZ304258B6 CZ2002-2740A CZ20022740A CZ304258B6 CZ 304258 B6 CZ304258 B6 CZ 304258B6 CZ 20022740 A CZ20022740 A CZ 20022740A CZ 304258 B6 CZ304258 B6 CZ 304258B6
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 87
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims description 34
- 238000002360 preparation method Methods 0.000 title claims description 21
- 230000008569 process Effects 0.000 title claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 7
- 238000011282 treatment Methods 0.000 claims abstract description 7
- 201000011510 cancer Diseases 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- -1 hydroxy, mercapto, amino, guanidino Chemical group 0.000 claims description 47
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 16
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- KZSNJWFQEVHDMF-SCSAIBSYSA-N D-valine Chemical compound CC(C)[C@@H](N)C(O)=O KZSNJWFQEVHDMF-SCSAIBSYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 229910052736 halogen Chemical group 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 4
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000005518 carboxamido group Chemical group 0.000 claims description 3
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 2
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
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- 230000004071 biological effect Effects 0.000 abstract description 6
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- RCGXNDQKCXNWLO-YUHQQKLOSA-N (2r)-n-[(2s)-5-amino-1-[[(2r,3s)-1-[[(3s,6z,9s,12r,15r,18r,19r)-9-benzyl-15-[(2s)-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-YUHQQKLOSA-N 0.000 abstract 2
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- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 34
- 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 description 32
- 238000002474 experimental method Methods 0.000 description 31
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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 22
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- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 19
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- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
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- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 17
- 238000007363 ring formation reaction Methods 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
- 229940079593 drug Drugs 0.000 description 15
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 14
- 125000003710 aryl alkyl group Chemical group 0.000 description 14
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- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 12
- 125000001151 peptidyl group Chemical group 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- UGNIYGNGCNXHTR-GOSISDBHSA-N (2r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@H](C(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UGNIYGNGCNXHTR-GOSISDBHSA-N 0.000 description 11
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- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- MHPUGCYGQWGLJL-UHFFFAOYSA-N 5-methyl-hexanoic acid Chemical compound CC(C)CCCC(O)=O MHPUGCYGQWGLJL-UHFFFAOYSA-N 0.000 description 10
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- SBYGJMHJIUKOGW-AJJAUPPJSA-N (2s)-2-[[(z)-2-[[(2s)-2-[[(2r)-2-[[(2r,3s)-2-[[(2r,3r)-2-[[(2r,3s)-2-[[(2s)-5-amino-2-[[(2r)-1-[(2s)-2-[[(2r)-2-[[(2r,3s)-3-hydroxy-2-[[(2s)-3-methyl-2-(5-methylhexanoylamino)butanoyl]amino]butanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]pyrrolid Chemical compound N([C@@H](CCCN)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@@H](C)O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N\C(=C/C)C(=O)N[C@@H](C(C)C)C(O)=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 SBYGJMHJIUKOGW-AJJAUPPJSA-N 0.000 description 9
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 9
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- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 8
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- ZPGDWQNBZYOZTI-GOSISDBHSA-N (2r)-1-(9h-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ZPGDWQNBZYOZTI-GOSISDBHSA-N 0.000 description 7
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- LZOLWEQBVPVDPR-VLIAUNLRSA-N (2s,3r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]butanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H]([C@H](OC(C)(C)C)C)C(O)=O)C3=CC=CC=C3C2=C1 LZOLWEQBVPVDPR-VLIAUNLRSA-N 0.000 description 7
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- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
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- 238000000825 ultraviolet detection Methods 0.000 description 1
- 150000003680 valines Chemical class 0.000 description 1
- ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical class C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K11/00—Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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)
- Animal Behavior & Ethology (AREA)
- 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)
- Steroid Compounds (AREA)
- Optical Record Carriers And Manufacture Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Saccharide Compounds (AREA)
- Silver Salt Photography Or Processing Solution Therefor (AREA)
- Detergent Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0002952.0A GB0002952D0 (en) | 2000-02-09 | 2000-02-09 | Process for producing kahalalide F compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ20022740A3 CZ20022740A3 (cs) | 2003-01-15 |
| CZ304258B6 true CZ304258B6 (cs) | 2014-02-05 |
Family
ID=9885232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ2002-2740A CZ304258B6 (cs) | 2000-02-09 | 2001-02-09 | Kahalalidová sloučenina, způsob její přípravy, farmaceutický prostředek ji obsahující a její použití |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US7482429B2 (enExample) |
| EP (3) | EP2258715A1 (enExample) |
| JP (1) | JP5188665B2 (enExample) |
| KR (1) | KR100871489B1 (enExample) |
| CN (2) | CN1422278A (enExample) |
| AT (1) | ATE371667T1 (enExample) |
| AU (1) | AU783542B2 (enExample) |
| BG (1) | BG65926B1 (enExample) |
| BR (1) | BR0108213A (enExample) |
| CA (1) | CA2399187C (enExample) |
| CY (1) | CY1106992T1 (enExample) |
| CZ (1) | CZ304258B6 (enExample) |
| DE (1) | DE60130192T2 (enExample) |
| DK (1) | DK1254162T3 (enExample) |
| ES (1) | ES2292558T3 (enExample) |
| GB (1) | GB0002952D0 (enExample) |
| HU (1) | HUP0301817A3 (enExample) |
| IL (2) | IL150981A0 (enExample) |
| MX (1) | MXPA02007760A (enExample) |
| NO (1) | NO331847B1 (enExample) |
| NZ (1) | NZ520488A (enExample) |
| PL (1) | PL207121B1 (enExample) |
| PT (1) | PT1254162E (enExample) |
| RU (1) | RU2280039C2 (enExample) |
| SK (1) | SK11242002A3 (enExample) |
| UA (1) | UA76949C2 (enExample) |
| WO (1) | WO2001058934A2 (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6274551B1 (en) * | 1994-02-03 | 2001-08-14 | Pharmamar, S.A. | Cytotoxic and antiviral compound |
| GB0002952D0 (en) * | 2000-02-09 | 2000-03-29 | Pharma Mar Sa | Process for producing kahalalide F compounds |
| US7473681B2 (en) | 2000-10-31 | 2009-01-06 | Pharma Mar, S.A. | Kahalalide F |
| 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 |
| US7507708B2 (en) * | 2003-02-26 | 2009-03-24 | Pharma Mar, S.A.U. | Antitumoral compounds |
| GB0321066D0 (en) * | 2003-09-09 | 2003-10-08 | Pharma Mar Sau | New antitumoral compounds |
| GB0408958D0 (en) * | 2004-04-22 | 2004-05-26 | Pharma Mar Sa | Convergent synthesis for kahalalide compounds |
| 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 |
| CN101861159A (zh) * | 2007-10-19 | 2010-10-13 | 马尔药品公司 | 改进的抗肿瘤治疗 |
| EP2252315A1 (en) * | 2008-01-30 | 2010-11-24 | Pharma Mar, S.A. | Improved antitumoral treatments |
| AU2009221120A1 (en) * | 2008-03-07 | 2009-09-11 | Pharma Mar, S.A. | Improved antitumoral treatments |
| 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 |
| CN108283000B (zh) | 2015-09-23 | 2021-04-13 | 凯瑞康宁生物工程（武汉）有限公司 | γ-羟基丁酸的前药及其组合物和用途 |
| KR102510784B1 (ko) | 2017-03-30 | 2023-03-15 | 엑스더블유파마 리미티드 | 이환형 헤테로아릴 유도체 및 이의 제조 및 용도 |
| LT3615544T (lt) | 2017-04-27 | 2023-05-10 | Pharma Mar S.A. | Priešnavikiniai junginiai |
| CN114042070A (zh) | 2018-09-30 | 2022-02-15 | 凯瑞康宁生物工程（武汉）有限公司 | 作为神经元组胺受体-3拮抗剂的化合物及其用途 |
| WO2021127461A1 (en) | 2019-12-20 | 2021-06-24 | Xw Laboratories Limited | Methods of synthesizing 4-valyloxybutyric acid |
| KR102982616B1 (ko) | 2020-06-18 | 2026-06-26 | 엑스더블유파마 리미티드 | 수용성 원료의약품의 약학적 과립화제 |
| AU2021292406B2 (en) | 2020-06-18 | 2024-03-14 | XWPharma Ltd. | Controlled release granulations of water-soluble active pharmaceutical ingredients |
| WO2022020621A1 (en) | 2020-07-24 | 2022-01-27 | XWPharma Ltd. | Pharmaceutical compositions and pharmacokinetics of a gamma-hydroxybutyric acid derivative |
| AU2021357705B2 (en) | 2020-10-05 | 2024-09-26 | XWPharma Ltd. | Modified release compositions of a gamma-hydroxybutyric acid derivative |
| DK4308086T3 (da) | 2021-03-19 | 2025-11-17 | Xwpharma Ltd | Farmakokinetik af formuleringer med kombineret frigivelse af et gamma-hydroxysmørsyrederivat |
| JP2025513295A (ja) * | 2022-04-21 | 2025-04-24 | ゼブラ セラピューティクス， インコーポレイテッド | ガンマ－ヒドロキシブチラート送達化合物ならびにその作製および使用のためのプロセス |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0610078A1 (en) * | 1993-02-03 | 1994-08-10 | Pharma Mar, S.A. | Cytotoxic and antiviral compound |
| EP1254162A2 (en) * | 2000-02-09 | 2002-11-06 | Pharma Mar, S.A. | Kahalalide f and related compounds |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US39496A (en) * | 1863-08-11 | Improvement in ratchet-drills | ||
| CU22545A1 (es) * | 1994-11-18 | 1999-03-31 | Centro Inmunologia Molecular | Obtención de un anticuerpo quimérico y humanizado contra el receptor del factor de crecimiento epidérmico para uso diagnóstico y terapéutico |
| US4943533A (en) * | 1984-03-01 | 1990-07-24 | The Regents Of The University Of California | Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor |
| JPS6178719A (ja) | 1984-09-25 | 1986-04-22 | Tanabe Seiyaku Co Ltd | 総合輸液剤 |
| 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 |
| AU658396B2 (en) * | 1991-03-06 | 1995-04-13 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Humanized and chimeric monoclonal antibodies |
| EP0567626B1 (en) * | 1991-11-19 | 2001-09-19 | Amylin Pharmaceuticals, Inc. | Amylin agonist peptides and uses therefor |
| US5849704A (en) | 1991-12-20 | 1998-12-15 | Novo Nordisk A/S | Pharmaceutical formulation |
| AU661533B2 (en) * | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| US6274551B1 (en) * | 1994-02-03 | 2001-08-14 | Pharmamar, S.A. | Cytotoxic and antiviral compound |
| US5932189A (en) * | 1994-07-29 | 1999-08-03 | Diatech, Inc. | Cyclic peptide somatostatin analogs |
| US5705511A (en) | 1994-10-14 | 1998-01-06 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| US5747498A (en) * | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| JP3927248B2 (ja) | 1995-07-11 | 2007-06-06 | 第一製薬株式会社 | Ｈｇｆ凍結乾燥製剤 |
| US6391874B1 (en) * | 1996-07-13 | 2002-05-21 | Smithkline Beecham Corporation | Fused heterocyclic compounds as protein tyrosine kinase inhibitors |
| US6235883B1 (en) * | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| WO1998050406A1 (en) * | 1997-05-09 | 1998-11-12 | The General Hospital Corporation | Cell proliferation related genes |
| RS49779B (sr) * | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| GB9803448D0 (en) | 1998-02-18 | 1998-04-15 | Pharma Mar Sa | Pharmaceutical formulation |
| US6200598B1 (en) * | 1998-06-18 | 2001-03-13 | Duke University | Temperature-sensitive liposomal formulation |
| CN1160338C (zh) * | 1998-11-19 | 2004-08-04 | 沃尼尔·朗伯公司 | N-[4-(3-氯-4-氟-苯基氨基)-7-(3-吗啉-4-基-丙氧基)-喹唑啉-6-基]-丙烯酰胺,不可逆的酪氨酸激酶抑制剂 |
| US7311924B2 (en) * | 1999-04-01 | 2007-12-25 | Hana Biosciences, Inc. | Compositions and methods for treating cancer |
| UA74803C2 (uk) * | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| JP2004514407A (ja) * | 2000-04-28 | 2004-05-20 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 異種キャプシド中にシュードタイピングされたａａｖ５キャプシドおよびａａｖ５ベクターを含む組換えａａｖベクター |
| US6440465B1 (en) * | 2000-05-01 | 2002-08-27 | Bioderm, Inc. | Topical composition for the treatment of psoriasis and related skin disorders |
| US7473681B2 (en) | 2000-10-31 | 2009-01-06 | Pharma Mar, S.A. | Kahalalide F |
| 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 |
| US7507708B2 (en) * | 2003-02-26 | 2009-03-24 | Pharma Mar, S.A.U. | Antitumoral compounds |
| GB0321066D0 (en) * | 2003-09-09 | 2003-10-08 | Pharma Mar Sau | New antitumoral compounds |
| GB0408958D0 (en) * | 2004-04-22 | 2004-05-26 | Pharma Mar Sa | Convergent synthesis for kahalalide compounds |
-
2000
- 2000-02-09 GB GBGB0002952.0A patent/GB0002952D0/en not_active Ceased
-
2001
- 2001-02-09 EP EP10178150A patent/EP2258715A1/en not_active Withdrawn
- 2001-02-09 DK DK01904169T patent/DK1254162T3/da active
- 2001-02-09 CZ CZ2002-2740A patent/CZ304258B6/cs not_active IP Right Cessation
- 2001-02-09 RU RU2002123877/04A patent/RU2280039C2/ru active
- 2001-02-09 NZ NZ520488A patent/NZ520488A/en not_active IP Right Cessation
- 2001-02-09 AU AU32086/01A patent/AU783542B2/en not_active Ceased
- 2001-02-09 US US10/182,881 patent/US7482429B2/en not_active Expired - Fee Related
- 2001-02-09 WO PCT/GB2001/000576 patent/WO2001058934A2/en not_active Ceased
- 2001-02-09 JP JP2001558081A patent/JP5188665B2/ja not_active Expired - Fee Related
- 2001-02-09 ES ES01904169T patent/ES2292558T3/es not_active Expired - Lifetime
- 2001-02-09 KR KR1020027010355A patent/KR100871489B1/ko not_active Expired - Fee Related
- 2001-02-09 HU HU0301817A patent/HUP0301817A3/hu unknown
- 2001-02-09 CN CN01807743A patent/CN1422278A/zh active Pending
- 2001-02-09 CN CN200810178807.9A patent/CN101597326B/zh not_active Expired - Fee Related
- 2001-02-09 BR BR0108213-2A patent/BR0108213A/pt not_active IP Right Cessation
- 2001-02-09 PT PT01904169T patent/PT1254162E/pt unknown
- 2001-02-09 DE DE60130192T patent/DE60130192T2/de not_active Expired - Lifetime
- 2001-02-09 EP EP01904169A patent/EP1254162B1/en not_active Expired - Lifetime
- 2001-02-09 EP EP07010878A patent/EP1829889A3/en not_active Withdrawn
- 2001-02-09 PL PL356800A patent/PL207121B1/pl unknown
- 2001-02-09 CA CA2399187A patent/CA2399187C/en not_active Expired - Fee Related
- 2001-02-09 AT AT01904169T patent/ATE371667T1/de active
- 2001-02-09 MX MXPA02007760A patent/MXPA02007760A/es active IP Right Grant
- 2001-02-09 IL IL15098101A patent/IL150981A0/xx unknown
- 2001-02-09 SK SK1124-2002A patent/SK11242002A3/sk not_active Application Discontinuation
- 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
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0610078A1 (en) * | 1993-02-03 | 1994-08-10 | Pharma Mar, S.A. | Cytotoxic and antiviral compound |
| EP1254162A2 (en) * | 2000-02-09 | 2002-11-06 | Pharma Mar, S.A. | Kahalalide f and related compounds |
Non-Patent Citations (3)
| Title |
|---|
| Goetz G. et al. Tetrahedron 55(25), 1999, 7739-7746 * |
| Hamann MT a Scheuer PJ J. Am. Chem. Soc. 115(13), 1993, 5825-5826 * |
| Hamann MT et al. J. Org. Chem. 61(19), 1996, 6594-6600 * |
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Legal Events
| Date | Code | Title | Description |
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| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20150209 |