- AN IMPROVED PROCESS FOR PREPARATION OF LIRAGLUTIDE
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The present invention relates to an improved process for the preparation of Liraglutide. The present invention further related an improved process for the preparation of substantially pure material having a purity of greater than or equal to 99.5% by HPLC.
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Page/Page column 11-12
(2021/07/02)
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- A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides
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A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C-labeled NiII-acyl complexes, formed from a 13CO insertion step with NiII-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of 13C-SilaCOgen or 13C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII-acyl complexes and the disulfide providing a reactive NiIII-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.
- Pedersen, Simon S.,Donslund, Aske S.,Mikkelsen, Jesper H.,Bakholm, Oskar S.,Papp, Florian,Jensen, Kim B.,Gustafsson, Magnus B. F.,Skrydstrup, Troels
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p. 7114 - 7123
(2021/03/03)
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- IMPROVED PROCESSES FOR THE PREPARATION OF PEPTIDE INTERMEDIATES/MODIFIERS
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The present application relates to improved processes for the preparation of peptide intermediates/modifier compounds of Formula (I) and their use in the synthesis of peptide derivatives. The present application further provides the compound of Formula I with high chemical purity of >98% and chiral purity of >99% and its use to make pharmaceutical peptide like Liraglutide.
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Page/Page column 15-16
(2020/10/21)
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- Preparation method of high-purity liraglutide side chain
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The invention discloses a preparation method of a high-purity liraglutide side chain, palmitic acid, N-hydroxysuccinimide and N, N'-diisopropylcarbodiimide are used as starting materials to react to obtain Palmitoyl-OSu, Palmitoyl-Glu-OtBu, Liraglutide side chain crude product Palmitoyl-Glu (OSu)-OtBu in sequence; the reaction solution is filtered, the obtained filtrate is washed with an acidic aqueous solution, and an organic phase is concentrated the until being dry; the organic phase is recrystallized by using an alkane and a fatty alcohol or a mixed solvent of the alkane and the fatty alcohol to obtain the high-purity liraglutide side chain. The method for preparing the high-purity liraglutide side chain is simple to operate, the synthesis period is short, the cost is low, the after-treatment is easy, the product purity can reach 99.41%, and the method can effectively remove HOSU, DIU, tetradecanoic acid impurities, L5-S2 and octadecanoic acid impurities and other unknown impurities, and is beneficial to large-scale production.
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Paragraph 0048-0049
(2019/07/04)
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- Novel GLP-1 Analogues
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The present disclosure pertains to novel Glucagon like Peptide-1 (GLP-1) (7-37) analogs having an amino acid sequence with Leu or Ile at the C-terminal. The new analogs are potent GLP-1 agonists with reduced adverse effect and improved duration of action. The present disclosure further relates to acylated derivatives of the new analogs which have further improved potency and duration of action and are suitable for oral administration. The analogs of present disclosure may be useful in treatment of diabetes and obesity.
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Paragraph 0117-0118
(2019/10/20)
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- INSULIN-INCRETIN CONJUGATES
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Insulin-incretin conjugates comprising a peptide having agonist activity at the glucagon-like 1 (GLP-1) receptor, the glucagon (GCG) receptor, and/or the gastric inhibitory protein (GIP) receptor conjugated to an insulin molecule having agonist activity at the insulin receptor and use of the conjugates for treatment of metabolic diseases, for example, Type 2 diabetes, are described.
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Page/Page column 98
(2017/10/11)
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- INSULIN DIMER-INCRETIN CONJUGATES
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Insulin dimers conjugated to peptides having at least one incretin activity are disclosed.
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Page/Page column 135
(2017/12/15)
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- Innovative chemical synthesis and conformational hints on the lipopeptide liraglutide
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Liraglutide is a new generation lipopeptide drug used for the treatment of type II diabetes. In this work, we describe new approaches for its preparation fully by chemical methods. The key step of these strategies is the synthesis in solution of the Lys/γ-Glu building block, Fmoc-Lys-(Pal-γ-Glu-OtBu)-OH, in which Lys and Glu residues are linked through their side chains and γ-Glu is Nα-palmitoylated. This dipeptide derivative is then inserted into the peptide sequence on solid phase. As liraglutide is obtained with great purity and high yield, our approach can be particularly attractive for an industrial production. We also report here the results of a circular dichroism conformational analysis in a membrane mimetic environment that offers new insights into the mechanism of action of liraglutide. Copyright
- Guryanov, Ivan,Bondesan, Alex,Visentini, Dario,Orlandin, Andrea,Biondi, Barbara,Toniolo, Claudio,Formaggio, Fernando,Ricci, Antonio,Zanon, Jacopo,Cabri, Walter
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p. 471 - 479
(2016/10/12)
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- POLYNUCLEOTIDE CONSTRUCTS HAVING BIOREVERSIBLE AND NON-BIOREVERSIBLE GROUPS
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The invention features a hybridized polynucleotide construct containing a passenger strand, a guide strand loadable into a RISC complex, and (i) a 3'-terminal or an internucleotide non-bioreversible group in the guide strand; or (ii) a 5'-terminal, a 3'-terminal, or an internucleotide non-bioreversible group in the passenger strand, and a 5'-terminal, a 3'-terminal, or an internucleotide disulfide bioreversible group in the guide strand or the passenger strand. The invention also features methods of delivering a polynucleotide to a cell using the hybridized polynucleotide construct. The invention further features methods of reducing the expression of a polypeptide in a cell using the hybridized polynucleotide construct.
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Page/Page column 180
(2016/02/19)
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- POLYNUCLEOTIDE CONSTRUCTS HAVING DISULFIDE GROUPS
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The invention features polynucleotide constructs containing one or more components (i) containing a disulfide linkage, where each of the one or more components is attached to an internudeotide bridging group or a terminal group of the polynucleotide construct, and each of the one or more components (i) contains one or more bulky groups proximal to the disulfide group. The invention also features polynucleotide constructs containing one or more components (i) containing a disulfide linkage, where each of the one or more components (i) is attached to an internudeotide bridging group or a terminal group of the polynucleotide construct, and each of the one or more components (i) contains at least 4 atoms in a chain between the disulfide linkage and the phosphorus atom of the internudeotide bridging group or the terminal group; and where the chain does not contain a phosphate, an amide, an ester, or an alkenylene. The invention also features methods of delivering a polynucleotide to a cell using the polynucleotide constructs of the invention.
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Page/Page column 174
(2015/05/26)
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- LYSINE-GLUTAMIC ACID DIPEPTIDE DERIVATIVES
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The invention relates to compounds of the formula to a process for making same and to the use of the products in the solid phase peptide synthesis. The compounds of formula I are versatile peptide intermediates for the solid phase peptide synthesis (SPPS) of peptide drugs which comprise a Glu-fatty alkyl side chain building block attached to a Lys-part of the peptide chain.
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- Lysin-glutamic acid dipeptide derivatives
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The invention relates to compounds of the formula to a process for making same and to the use of the products in the solid phase peptide synthesis. The compounds of formula I are versatile peptide intermediates for the solid phase peptide synthesis (SPPS) of peptide drugs which comprise a Glu-fatty alkyl side chain building block attached to a Lys-part of the peptide chain.
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- Conjugates for cancer therapy and diagnosis
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The present invention relates to conjugates of a drug and an amino acid or an amino acid derivative or analog, pharmaceutical compositions that include the conjugates and methods of use thereof. In particular, the present invention relates to conjugates o
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Page/Page column 13
(2010/11/26)
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- GLP-2 COMPOUNDS, FORMULATIONS, AND USES THEREOF
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The present invention relates to novel compositions comprising human glucagon-like peptide-2 (GLP-2) peptides, pharmaceutical compositions, and uses of these and other GLP-2 compounds, compositions and formulations, including methods of treating gastrointestinal disorders and increasing nutrient absorption therewith.
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Page/Page column 99
(2008/06/13)
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