- Monodisperse oligoethylene glycols modified Camptothecin, 10-Hydroxycamptothecin and SN38 prodrugs
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Camptothecin, which represents a class of natural products with high anticancer activity, suffers low water solubility which hampers its clinic application. To address this issue, monodisperse polyethylene glycols were employed to modify this class of natural products, including Camptothecin, 10-Hydroxycamptothecin, and SN38. Through selective modification with a series of monodisperse polyethylene glycols, 31 Camptothecin derivatives, including 9 ethers and 22 carbonates, were prepared using a macrocyclic sulfate-based strategy with high efficacy. Monodisperse polyethylene glycols modification provided the Camptothecin derivatives with high purity and fine-tunable water solubility. Through the physicochemical and biological assays, a few novel prodrugs with good solubility, cytotoxicity, and valuable drug release profile were identified as promising anticancer drug candidates.
- Deng, Tao,Mao, Xianglan,Xiao, Yan,Yang, Zhigang,Zheng, Xing,Jiang, Zhong-Xing
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p. 581 - 584
(2019/01/04)
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- Monodisperse oligoethylene glycols modified Propofol prodrugs
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The low water solubility of Propofol resulted in complicated formulation and adverse effects during its clinical application. To improve its water solubility and maintain its anesthetic effects, Propofol prodrugs with monodisperse oligoethylene glycols as solubility enhancer were designed and synthesized. Monodisperse oligoethylene glycols enable the concise manipulation of water solubility, biocompatibility and anesthetic effects. Through the physicochemical and biological assay, a few water soluble prodrugs of Propofol were identified as promising anesthetic to overcome the drawbacks associated with Propofol.
- Deng, Tao,Mao, Xianglan,Li, Yu,Bo, Shaowei,Yang, Zhigang,Jiang, Zhong-Xing
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p. 3502 - 3505
(2018/10/15)
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- Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
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Pharmaceutical compositions that include an insulin drug-oligomer conjugate, a fatty acid component, and a bile salt component are described. The insulin drug is covalently coupled to an oligomeric moiety. The fatty acid component and the bile salt component are present in a weight-to-weight ratio of between 1:5 and 5:1. Methods of treating an insulin deficiency in a subject in need of such treatment using such pharmaceutical compositions are also provided, as are methods of providing such pharmaceutical compositions.
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- Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
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Pharmaceutical compositions that include insulin, an insulin drug-oligomer conjugate, a fatty acid component, and a bile salt component or a bile salt component without a fatty acid component are described. The insulin drug is covalently coupled to an oligomeric moiety. The fatty acid component and the bile salt component, when together, can be present in a weight-to-weight ratio of between 1:15 and 15:1. Methods of treating an insulin deficiency in a subject in need of such treatment using such pharmaceutical compositions are also provided, as are methods of providing such pharmaceutical compositions.
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- Pharmaceutical compositions of drug-oligomer conjugates and methods of treating diseases therewith
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Pharmaceutical compositions that include a drug-oligomer conjugate, a fatty acid component, and a bile salt component are described. The drug is covalently coupled to an oligomeric moiety. The fatty acid component and the bile salt component are present in a weight-to-weight ratio of between 1:5 and 5:1. Methods of treating diseases in a subject in need of such treatment using such pharmaceutical compositions are also provided, as are methods of providing such pharmaceutical compositions.
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- Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
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Methods for synthesizing proinsulin polypeptides are described that include contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also provided as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates and other pro-polypeptide-oligomer conjugates are also provided.
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- Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
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Methods for synthesizing proinsulin polypeptides are described that include a contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also described as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates are also described.
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- Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
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Methods for synthesizing proinsulin polypeptides are described that include contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also provided as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates and other pro-polypeptide-oligomer conjugates are also provided.
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- Substituted (1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl)phenyl derivatives, their preparation and their use in treatment of inflammatory conditions and immune disorders
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The present invention provides a compound of formula (I) or a solvate thereof wherein: X is —O— or —NH—; Q is (—CH2—)p, (—CH═CH—)p, (—C≡C—)pwhere p is an integer of from 0 to 4; R1is hydrogen or methyl; R2and R3independently represent O or S n is an integer of 1 to 50; and R is hydrogen or methyl. The present invention also provides pharmaceutical compositions and methods of treatment using the compounds of formula (I). The compounds of the present invention are useful for the prophylaxis and treatment of septic shock, inflammatory conditions and immune disorders.
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Page column 12
(2008/06/13)
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