- Synthesis, characterization and topical application of novel bifunctional peptide metallodendrimer
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Present research work focuses on the synthesis of lower generation bifunctional peptide metallodendrimer followed by its characterization using IR, Mass and NMR (1H and 13C) and finally exploring it for treating acne and wounds. Metallodendrimer was formulated into Tamarind Seed Polysaccharide (TSP) based hydrogel at 7% w/w concentration and analyzed for its properties of spreadability and bioadhesion. Testing of in-vitro antibacterial activity, sterility, in-vivo wound healing efficacy and stability studies followed the formulation development stage. The explored peptide metallodendrimer is a complex of second generation lysine dendrimers and zinc, exhibiting antibacterial activity against Propionibacterium acne, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. In-vivo wound healing studies in comparison with marketed product indicated significant performance by metallodendrimer with respect to percent re-epithelization and wound contracture. The results were supported by concurrent improvement in various histopathological parameters such as cellularity, granulation, epithelization, vascular density, collagen staining intensity with less number of average mast cells and absence of scar formation. A bifunctional peptide metallodendrimer based platform technology was fabricated and duly evaluated for potential activities.
- Pandya, Anjali,Patravale, Vandana,Pukale, Sudeep
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- Understanding the binding properties of phosphorylated glycoluril-derived molecular tweezers and selective nanomolar binding of natural polyamines in aqueous solution
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A modular synthetic platform for the construction of flexible glycoluril-derived molecular tweezers was developed. The binding properties of four exemplary supramolecular hosts obtained via this approach towards 16 organic amines were investigated by means of 1H NMR titration. In this work, we compare the Ka values obtained this way with those of three structurally related molecular tweezers and provide a computational approach towards an explanation of the observed behavior of those novel hosts. The results showcase that certain structural modifications lead to very potent and selective binders of natural polyamines, with observed binding of spermine below 10 nM. This journal is
- Heilmann, Michael,Knezevic, Melina,Piccini, Giovannimaria,Tiefenbacher, Konrad
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supporting information
p. 3628 - 3633
(2021/05/04)
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- NOVEL DRUG DELIVERY CONJUGATED MOIETY FOR ORAL ADMINISTRATION OF DRUG UNSUITABLE FOR ORAL ADMINISTRATION AND PREPARATION METHOD THEREOF
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The present invention provides a novel drug delivery conjugated moiety for oral administration of a drug that is not suitable for oral administration or a pharmaceutically acceptable salt thereof. When the drug delivery conjugated moiety of the present invention or a pharmaceutically acceptable salt thereof is combined with a drug, which is not suitable for oral administration, and is administered orally, it exhibits an excellent absorption rate without decreasing the biological activities of the drug. Moreover, the drug delivery conjugated moiety of the present invention or a pharmaceutically acceptable salt thereof can be easily prepared in a few steps, which is very advantageous in terms of mass production.
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Paragraph 70; 71; 72; 73
(2017/02/09)
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- Supramolecular self-assembly of chiral polyimides driven by repeat units and end groups
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Pyromellitic diimides (PMDIs) are effective building blocks for the construction of supramolecular systems but are infrequently used in comparison with other electron-deficient aromatic systems. We report PMDI-based chiral polyimides that form polymeric supramolecular systems with unique self-assembly features that show time-dependent spectroscopic behaviour. Extensive investigations revealed the driving forces for the self-assembly of the polyimides. One is the complementary aromatic π-π stacking between electron-accepting PMDI and electron-donating phenyl ring in the polymer backbones, and another is the hydrogen bonding interactions of the end groups. The self-assembly is readily disrupted by guest molecules with strong associations with the PMDI and the end groups. The introduction of flexible arylether diimides into the PMDI-based copolymer backbones and the sequence of PMDIs and arylether diimides in the copolymer backbones significantly influence the self-assembly of the polyimides. The results elucidate the mechanisms of polymeric self-assembly of chiral polyimides, providing important information for the development of materials based on polymeric supramolecular systems with properties and functions regulated by composition, sequence and end groups.
- Yan, Jijun,Kang, Chuanqing,Bian, Zheng,Jin, Rizhe,Ma, Xiaoye,Gao, Lianxun
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supporting information
p. 14723 - 14729
(2017/11/28)
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- Novel chiral derivatizing agents for 1H NMR determination of enantiomeric purities of carboxylic acids
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(S)-4-(3-Aminopyrrolidin-1-yl)coumarin (1), (S)-4-(3-aminopiperidin-1-yl)coumarin (4), and (S)-4-(3-aminoazepan-1-yl)coumarin (7), prepared from 4-chlorocoumarin and (S)-pyrrolidin-3-amine, (S)-piperidin-3-amine, and (S)-azepan-3-amine, respectively, were proven to be versatile and reliable 1H NMR optical purity determination agents for chiral carboxylic acids.
- Wada, Koji,Goto, Mizuko,Yamashita, Hiroshi,Nagasawa, Kazuo
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p. 964 - 978
(2017/06/13)
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- AMINO ACID DERIVATIVES AND ABSORBABLE POLYMERS THEREFROM
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The present invention relates to the discovery of new class of hydrolysable amino acid derivatives and absorbable polyester amides, polyamides, polyepoxides, polyureas and polyurethanes prepared therefrom. The resultant absorbable polymers are useful for drug delivery, tissue engineering, tissue adhesives, adhesion prevention, bone wax formulations, medical device coatings, stents, stent coatings, highly porous foams, reticulated foams, wound care, cardiovascular applications, orthopedic devices, surface modifying agents and other implantable medical devices. In addition, these absorbable polymers should have a controlled degradation profile.
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Paragraph 0188; 0189; 0226; 0227
(2016/09/26)
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- Radical arylation of tyrosine residues in peptides
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The radical arylation of the phenolic side chain of tyrosine in peptides was investigated. Aryl radicals were generated from aryldiazonium salts using titanium(III) chloride as stoichiometric reductant. Due to the high selectivity with which 3-aryltyrosine derivatives were formed, this reaction type represents a new strategy for the direct functionalization of peptides.
- Fehler, Stefanie K.,Pratsch, Gerald,?streicher, Christiane,Fürst, Michael C.D.,Pischetsrieder, Monika,Heinrich, Markus R.
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supporting information
p. 7888 - 7893
(2016/11/17)
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- Novel aminopeptidase N inhibitors with improved antitumor activities
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A series of aminopeptidase N (APN) inhibitors were designed and synthesized. Enzyme inhibitory, docking and antiproliferative studies were performed to evaluate the derived molecules. Molecule D15, with IC50 values of 10.9 μM, showed the best performance in the APN enzymatic inhibition assay. The binding pattern of molecule D9 and D15 in the active site of APN was predicted by docking studies. Hydrophobic and H-bond interactions were discovered to make key roles in the ligand-receptor bindings. Compared with the previous C7, several molecules such as D9, D14 and D15, exhibited significantly improved activities in inhibiting the growth of HL-60, ES-2, A549 and PLC cell lines.
- Wang, Qiang,Shi, Qiao,Huang, Lu
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- A simple synthesis of 6-hydroxynorleucine based on the rearrangement of an N-nitrosodichloroacetamide
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6-Hydroxynorleucine is a versatile chemical intermediate that has found broad use in target-oriented syntheses of numerous biologically active molecules. Despite its widespread use, and despite the various strategies that have been reported for its prepar
- McCarthy, Blaine G.,Macarthur, Nicholas S.,Jakobsche, Charles E.
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supporting information
p. 502 - 504
(2016/01/12)
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- Synthesis and properties of bis-porphyrin molecular tweezers: Effects of spacer flexibility on binding and supramolecular chirogenesis
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Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar enediyne (1), the helical stiff stilbene (2), or the semi-rigid glycoluril motif fused to the porphyrins (3), are compared. Binding constants Ka = 104-106 M-1 reveal subtle differences between these tweezers, that are discussed in terms of porphyrin dislocation modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.
- Blom, Magnus,Norrehed, Sara,Andersson, Claes-Henrik,Huang, Hao,Light, Mark E.,Bergquist, Jonas,Grennberg, Helena,Gogoll, Adolf
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supporting information
(2016/02/05)
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- Amino acid ester bromination salt chiral ionic liquid and its preparation method
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The invention discloses amino-acid ester bromide type chiral ionic liquid and a preparation method thereof. The general formula of the amino-acid ester bromide type chiral ionic liquid is ABr, wherein A is an amino-acid ester positive ion. The preparation method comprises the following steps: performing reaction on amino acid, methyl alcohol and thionyl chloride under low temperature to obtain amino-acid ester hydrochloride; performing mannich reaction on amino-acid ester hydrochloride, paraformaldehyde and acetone to obtain amino-acid ester mannich base; performing reaction on amino-acid ester mannich base and bromo-hydrocarbon to obtain the amino-acid ester chiral ionic liquid. The chiral amino-acid ester ionic liquid prepared through the preparation method disclosed by the invention has the advantages of high selectivity and chiral induction effect of a chiral substance, and non-volatilization, non-toxicity and no pollution of ionic liquid and is suitable for scale production of the fine chemical industry.
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Paragraph 0046-0049; 0056
(2018/02/04)
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- Lysine-based functional blocked isocyanates for the preparation of polyurethanes provided with pendant side groups
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This article describes a methodology to prepare polyurethanes (PUs), decorated with pendant (bio)functional side groups, by polymerizing (bio)functionalized blocked diisocyanates with polyols. Caprolactam blocked lysine diisocyanate methyl ester (BLDI-OMe) was prepared in high yields, by reacting the methyl ester of lysine with carbonyl biscaprolactam. In the absence of a catalyst, the polymerization of BLDI-OMe with polycaprolactone and polytetrahydrofuran resulted in strictly linear PUs due to the high selective reactivity of the blocked isocyanates (BIs). Although the ester appeared to be less reactive, we found hydrolyzing conditions for the ester, without affecting the BIs. The free acid groups were converted into a N-hydroxysuccinimide (NHS) activated ester, which was a versatile intermediate for further functionalization. After having demonstrated that model amines were able to substitute NHS without effecting the BIs groups, the same chemistry was used to couple biotin, giving a biotin functional caprolactam blocked lysine diisocyanate. The polymerization with polyols afforded the corresponding biotin-functional PUs.
- Yin, Jie,Wildeman, Jur,Loontjens, Ton
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p. 2036 - 2049
(2015/08/03)
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- Bis-3-chloropiperidines containing bridging lysine linkers: Influence of side chain structure on DNA alkylating activity
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A series of bis-3-chloropiperidines containing lysine linkers was synthesised as DNA alkylating model compounds by using a bidirectional synthetic strategy. These novel piperidine mustard based agents have been evaluated for their alkylating properties towards nucleic acids and were shown to alkylate and cleave DNA with strong preference for guanine residues. Our studies reveal that the introduction of aromatic groups in the side chain of the lysine linker has an impact on DNA alkylating activity. Analysis by ESI mass spectrometry enabled the verification of the reactive aziridinium ion formation. Overall, the results confirm our recently proposed reaction mechanism of bis-3-chloropiperidines.
- Zuravka, Ivonne,Roesmann, Rolf,Sosic, Alice,G?ttlich, Richard,Gatto, Barbara
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p. 1241 - 1250
(2015/03/04)
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- Synthesis and characterization of captopril derivatives
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To develop more potential angiotensin converting enzyme (ACE) inhibitors, a series of captopril (Cap) derivatives were synthesized, including Cap-glycine methyl ester, Cap-l-alanine methyl ester, Cap-l-aspartic acid dimethyl ester, Cap-l-lysine methyl ester, Cap-O-acylisourea, acetyl captopril, and benzoyl captopril. The resulting products were characterized by IR and UV-visible spectroscopy and MS, which showed the desired products were successfully synthesized. This could serve as a guide for rational design of highly potent ACE inhibitors.
- Li, He-Ping,Zhang, Juan-Juan,Qin, Long,Zhao, Ming-Dong
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p. 621 - 629
(2013/07/27)
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- Synthesis, characterization and pharmacological evaluation of amino acid conjugates of ketoprofen
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Ketoprofen is used for its antipyretic, analgesic and antiinflammatory properties by inhibiting cyclooxygenase-1 and cyclooxygenase-2 enzymes reversibly, which decreases production of proinflammatory prostaglandin precursors. Ketoprofen suffers from the general side effects of nonsteroidal antiinflammatory drugs, owing to presence of free carboxylic acid group. The study aimed to retard the adverse effects of gastrointestinal origin. Different conjugates of ketoprofen have been synthesized by amidation with methyl esters of amino acids namely, phenylalanine, lysine, arginine, glycine, cysteine, valine, glutamine, serine, proline and alanine. Synthesized conjugates were characterized and evaluated for analgesic and antiinflammatory activities.
- Dubey,Jain,Bhadoria,Sinha
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experimental part
p. 1170 - 1174
(2012/08/28)
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- Synthesis, characterization and biological evaluation of amino acid conjugates of mefenamic acid
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Mefenamic acid is used for its antipyretic, analgesic, antiinflammatory properties and also inhibits cyclooxygenase-1 and cyclooxygenase- 2 (COX-1 and COX-2) enzymes reversibly, which decreases production of pro-inflammatory prostaglandin precursors. Mefenamic acid suffers from the general side effects of non-steroidal antiinflammatory drugs, owing to presence of free carboxylic acid group. The study aimed to retard the adverse effects of gastrointestinal origin. Amino acid conjugates of mefenamic acid were synthesized by amidation with methyl esters of amino acids namely, phenylalanine, cysteine, glycine, lysine, arginine, valine, proline, serine, alanine and methionine. Synthesized conjugates were characterized by melting point, TLC, 1H NMR and mass spectroscopy. Synthesized conjugates were also evaluated for their analgesic and antiinflammatory activities. Comparable analgesic and anti-inflammatory activities were obtained as compared to mefenamic acid.
- Dubey, Nitin,Jain, Dinesh K.,Bhadoriya, Upendra S.,Solanki, Balvant
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experimental part
p. 1237 - 1241
(2012/09/07)
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- Tridentate lysine-based fluorescent sensor for Hg(II) in aqueous solution
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A novel homoplastic podand fluorescent sensor based on flexible hydrophilic lysine was prepared. Lysine with two dansyl groups-appended at both ends supplied a possibility for a tridentate binding toward Hg(II) and finally resulted in a unique selectivity
- Chen, Liping,Yang, Liting,Li, Hongwei,Gao, Yang,Deng, Dayi,Wu, Yuqing,Ma, Li-Jun
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experimental part
p. 10028 - 10032
(2011/12/01)
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- Copolymerization of CO2 and cyclohexene oxide using a lysine-based (salen)CrIIICl catalyst
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A new, natural lysine-based (salen)CrIIICl ((lys-salen)Cr IIICl) complex was prepared and its catalytic activity for the copolymerization of CO2 and cyclohexene oxide (CHO) was described in the presence of PPNCl (PPN+
- Guo, Liping,Wang, Congmin,Zhao, Wenjia,Li, Haoran,Sun, Weilin,Shen, Zhiquan
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experimental part
p. 5406 - 5410
(2009/12/06)
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- FUNCTIONALIZED NON-PHENOLIC AMINO ACIDS AND ABSORBABLE POLYMERS THEREFROM
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The present invention relates to compound of formula I, which are functionalized, non-phenolic amino acids, and polymers formed from the same. Polymers formed from the functionalized amino acids are expected to have controllable degradation profiles, enab
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Page/Page column 10
(2010/11/30)
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- Iminosugar glycoconjugates
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The iminosugar conjugates according to the invention are N-alkylated 1,5-dideoxy-1,5-iminohexitol or 1,5-dideoxy-1,5-iminopentitol derivatives. The iminosugar component can be, for example, D-gluco-, L-ido-, D-galacto-, D-manno-, 2-acetamido-2-deoxy-D-gluco- or xylo-configuration. The N-substituent is a protected L-α-aminoacid derivative, showing L-lysine-like structural features. The linkage between the carbohydrate and the peptide component is not via the usual glycosidic position, but shows structural features of a very stable tertiary amine. Thus the linkage is very stable. These new compounds are synthesised by using catalytic intramolecular reductive amination of dicarbonyl sugars with partially protected amino acids. The process of intramolecular reductive amination itself is carried out using Pearlman's catalyst (Pd(OH)2/C) and H2 at ambient pressure and room temperature. The resulting accessible class of iminosugar conjugate compounds is represented by the general structure shown in Figure 4(c). The alkyl chain length parameter n can be freely chosen from n=0 upwards. Preferably n is between 0 and 10, and more preferably n is 2, 3, or 4. Residue R1 can be chosen from H, OH, or NHAc, with Ac being Acetyl. R2 can be H, OH, or NHAc. R3, R4, R5, R6 can be H or OH. R7 and R8 can be H, CH2OH CH3, COQH, or COOR with R being Alkyl or Aryl. R9 and R10 can be chosen from H, NH2, NHR, with R being a protective group, an amino acid, a peptide, or a protein. R11 can be OH, O-Alkyl, O-Aryl, NH2, N-Alkyl, N-Aryl, amino acid or peptide, connected via an amide bond.
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Page/Page column 7
(2008/06/13)
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- Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives
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We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.
- McGuigan, Christopher,Hassan-Abdallah, Alshaimaa,Srinivasan, Sheila,Wang, Yikang,Siddiqui, Adam,Daluge, Susan M.,Gudmundsson, Kristjan S.,Zhou, Huiqiang,McLean, Ed W.,Peckham, Jennifer P.,Burnette, Thimysta C.,Marr, Harry,Hazen, Richard,Condreay, Lynn D.,Johnson, Lance,Balzarini, Jan
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p. 7215 - 7226
(2007/10/03)
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- Design, synthesis, and biological evaluation of chicoric acid analogs as inhibitors of HIV-1 integrase
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A series of analogs of the potent HIV-1 integrase (HIV IN) inhibitor chicoric acid (CA) was designed with the intention of ameliorating some of the parent natural product's undesirable properties, in particular its toxicity, instability, and poor membrane
- Charvat, Trevor T.,Lee, Deborah J.,Robinson, W. Edward,Chamberlin, A. Richard
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p. 4552 - 4567
(2007/10/03)
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- Synthesis of a methacrylic monomer containing an L-lysine-based dendron
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Procedures were developed for preparing a polylysine dendron of second generation, containing terminal Boc-protected amino groups and a free focal amino group; from this substance, a previously unknown methacrylic monomer linked to the L-lysine-based dendron was prepared.
- Khimich,Tennikova
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p. 1003 - 1007
(2007/10/03)
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- Functionalized derivatives of hyaluronic acid, formation of hydrogels in situ using same, and methods for making and using same
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Methods for chemical modification of hyaluronic acid, formation of amine or aldehyde functionalized hyaluronic acid, and the cross-linking thereof to form hydrogels are provided. Functionalized hyaluronic acid hydrogels of this invention can be polymerized in situ, are biodegradable, and can serve as a tissue adhesive, a tissue separator, a drug delivery system, a matrix for cell cultures, and a temporary scaffold for tissue regeneration.
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- HIV protease inhibitors based on amino acid derivatives
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A compound selected from the group consisting of a compound of formula I 1a compound of formula II 2and when the compound of formula I and II comprises an amino group pharmaceutically acceptable ammonium salts thereof, wherein R1, R2, Cx, n, R3, R4, R5, Y are as defined in the specification.
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- Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and hiv-1 replication at nontoxic concentrations
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The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 μM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two biscatechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of L-chicoric acid (L-CA) showed improved selectivity over L-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.
- Reinke, Ryan A.,King, Peter J.,Victoria, Joseph G.,McDougall, Brenda R.,Ma, Guoxiang,Mao, Yingqun,Reinecke, Manfred G.,Robinson Jr., W. Edward
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p. 3669 - 3683
(2007/10/03)
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- A chiral sensor for arginine and lysine
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(Graph presented) We provide access to a new class of C1-or C2-symmetrical host molecules 1 and 2 based on a spirobisindane skeleton. Whereas 1 is selective for short, rigid diamines, 2 prefers longer α,ω-dications. Of all the amino acid methyl esters, only those of lysine and arginine with the correct distance between their cationic groups form strong 1:1 complexes in DMSO with 2. NMR titrations reveal high association constants as well as discrimination between the enantiomers of lysine and arginine.
- Wehner, Mark,Schrader, Thomas,Finocchiaro, Paolo,Failla, Salvatore,Consiglio, Giuseppe
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p. 605 - 607
(2007/10/03)
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- Convenient preparations of racemic and enantiopure methyl 6-oxopipecolate
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Short, convenient syntheses of racemic and enantiopure methyl 6-oxopipecolate are described, starting from either pipecolic acid or (S)-lysine respectively. The sequence for the latter compound relies upon improved methodology for the oxidation of C-6 of
- Davies, Catherine E.,Heightman, Thomas D.,Hermitage, Stephen A.,Moloney, Mark G.
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p. 687 - 696
(2007/10/03)
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- Preparation and isolation of mineral acid salt of an amino acid methyl ester
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A cyclical process for producing and isolating a mineral acid salt of an amino acid methyl ester in high purity and yield from the reaction solution produced by esterifying an amino acid with methanol in methanol in the presence of a mineral acid, by cooling the resulting reaction solution to precipitate crystals of the mineral acid salt; filtering the crystals; drying the isolated wet crystals or washing with another organic solvent; and recycling the filtrate for reuse in the esterification reaction.
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- SYNTHESIS OF CHIRAL THIOCARBAMOYLPHOSPHINES DERIVED FROM AMINO ACIDS
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The methylester hydrochlorides of the (S)-amino acids L-alanine (1a), L-phenylalanine (1b), L-valine (1c) and L-lysine (1d) were converted to the corresponding isothiocyanates 2a-d by thiophosgenation. 2a-d React with secondary phosphines and phosphine oxides to give the thiocarbamoylphosphines 3a-d and P-oxides 4a, b.
- Kunze, U.,Burghardt, R.
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p. 373 - 376
(2007/10/02)
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- Method for producing lysine ester
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Lysine ester is produced by heating α-amino-ε-capro-lactam with an alcohol. The reaction can be accelerated by adding a small amount of water and an acid or base catalyst.
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