- HYALURONIC ACID DERIVATIVE AND DRUG CONTAINING THE SAME
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The present invention relates to a hyaluronic acid derivative in which an anti-inflammatory drug is bound via a covalent bond, wherein the structure of the hyaluronic acid derivative is represented by following formula (4) or (5): ???????? HA-SP-NSAID?????(4) ???????? HA-SP-DMARD?????(5) wherein HA represents a hyaluronic acid chain; SP represents a spacer residue; NSAID represents a non-steroidal anti-inflammatory drug residue, DMARD represents a disease-modifying anti-rheumatic drug residue, and - represents the covalent bond, wherein the spacer binds to a carboxyl group of the hyaluronic acid via an amide bond and the anti-inflammatory drug selected from non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs binds to the spacer via an ester bond, an amide bond or a thioester bond.
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Paragraph 0148
(2018/09/08)
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- Pharmacomodulation of the antimalarial plasmodione: Synthesis of biaryl-and N-arylalkylamine analogues, antimalarial activities and physicochemical properties
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With the aim of increasing the structural diversity on the early antimalarial drug plasmodione, an efficient and versatile procedure to prepare a series of biaryl- and N-arylalkylamines as plasmodione analogues is described. Using the naturally occurring and commercially available menadione as starting material, a 2-step sequence using a Kochi-Anderson reaction and subsequent Pd-catalyzed Suzuki-Miyaura coupling was developed to prepare three representative biphenyl derivatives in good yields for antimalarial evaluation. In addition, synthetic methodologies to afford 3-benzylmenadione derivatives bearing a terminal -N(Me)2 or -N(Et)2 in different positions (ortho, meta and para) on the aryl ring of the benzylic chain of plasmodione were investigated through reductive amination was used as the optimal route to prepare these protonable N-arylalkylamine privileged scaffolds. The antimalarial activities were evaluated and discussed in light of their physicochemical properties. Among the newly synthesized compounds, the para-position of the substituent remains the most favourable position on the benzyl chain and the carbamate -NHBoc was found active both in vitro (42 nM versus 29 nM for plasmodione) and in vivo in Plasmodium berghei-infected mice. The measured acido-basic features of these new molecules support the cytosol-food vacuole shuttling properties of non-protonable plasmodione derivatives essential for redox-cycling. These findings may be useful in antimalarial drug optimization.
- Urgin, Karène,Jida, Mouhamad,Ehrhardt, Katharina,Müller, Tobias,Lanzer, Michael,Maes, Louis,Elhabiri, Mourad,Davioud-Charvet, Elisabeth
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- Method for preparing 4-acetylaminophenylacetic acid
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The invention discloses a method for preparing 4-acetylaminophenylacetic acid. The method includes the steps that p-nitrophenylacetic acid, N,N-dimethylacetamide and ammonium chloride are evenly mixed, heating reflux, cooling and crystallizing are conducted, and crystals are obtained to obtain 4-acetylaminophenylacetic acid. The production cost is low, the yield is high, product purity is good, operation is easy, the production period is short, and the method is suitable for industrial mass production.
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Paragraph 0029-0030
(2017/05/26)
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- Boron trifluoride-methanol complex. Mild and powerful reagent for deprotection of acetylated amines. Scope and selectivity
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A boron trifluoride-methanol complex demonstrated remarkable deprotection selectivity against commonly used amino-protecting groups in the deacetylation of acetanilides and high sensitivity to the steric hindrance of substrates. The scope and limitations of the reaction were explored.
- Miltsov, Sergey,Karavan, Vladimir,Misharev, Alexandr,Alonso-Chamarro, Julian,Puyol, Mar
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supporting information
p. 641 - 644
(2016/01/26)
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- ROR-GAMMA MODULATORS AND USES THEREOF
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The present invention relates to a compound of formula I, or an isotopic form, stereoisomer, a tautomer, a pharmaceutically acceptable salt, a solvate, a polymorph, a prodrug, N-oxide or S-oxide thereof; and processes for their preparation. The invention further relates to pharmaceutical compositions containing the compounds and their use in the treatment of diseases or disorders mediated by RORγ.
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Page/Page column 40
(2016/01/21)
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- A novel method for the synthesis of actarit
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The specific synthetic route to synthesize the actarit (4-acetyl-amino phenylacetic acid) by acylation was designed in which p-amino benzaldehyde (a) and nitromethane (b) was used as the raw materials, through Knoevenagel reaction. The selective reduction of potassium borohydride and p-amino phenylacetic acid to be oxidated under the acidic conditions. After optimization of the synthetic conditions, the yield of each step was more than 85 %. The synthesized compound was confirmed by the elemental analysis and nuclear magnetic resonance. Because of the readily available raw materials, simple operations, high yield and avoiding highly toxic reagents in the synthesis of actarit (4-acetyl-amino phenylacetic acid), the synthetic route is suitable for the industrial production.
- Zhou, Li-Yi,Yang, Jun,Yan, Xi-Qing,Pan, Yan-Juan,Wu, Feng,Zhang, Jing,Yan, Fu-Lin,Lu, Guang-Zhou
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p. 1538 - 1540
(2012/10/07)
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- 2-PHENYL BENZOYLAMIDES
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Compounds of Formula I that inhibit microsomal triglyceride transfer protein (MTP) and/or apolipoprotein B (Apo B) secretion and their uses in the treatment of diseases linked thereto in animals are described herein.
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Page/Page column 69
(2011/12/04)
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- Microwave-assisted synthesis of amide under solvent-free conditions
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An efficient and environmentally friendly synthetic method for the synthesis of primary amides under microwave irradiation was described, in which the primary amine was directly reacted with acid without any catalytic agents. The reaction took place in 8-12-min, which was much shorter than the traditional synthetic methods, with almost quantitative yields. The influential factor of the reaction was discussed. The tautomerization between the carboxylic acid group and the H atom in α-carbon of L-amino acid was observed, presumably a dehydrated intermediate forming from this tautomerized isomer. Copyright Taylor & Francis Group, LLC.
- Wang, Xiao-Jian,Yang, Qian,Liu, Fei,You, Qi-Dong
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p. 1028 - 1035
(2008/09/18)
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- DERIVATIVES OF ACTARIT AND THEIR THERAPEUTIC USE
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Compounds that may have anti-inflammatory activity are of general formula wherein X is O or NR1; Y isOorNR1; R2 is OR1 or C,1-4 alkyl substituted with R3, and R2 is optionally substituted With R4; each R1 is the same or different and is H or C1-4 alkyl, or R1 and R2 are joined to form a four to seven-membered ring containing one or more additional heteroatoms selected from O, N and S, and is optionally substituted with R7; R3is OR4, NR5R6 or a four to seven- embered ring which can contain .one or morte heteroatoms selected from O, N and S, and is optionally substituted with R7;R4 is H or C1-4 alkyl optionally substituted with OR8; R5 and R6 are the same or different and are each selected from H and C1-4 alkyl optionally substituted with OR8; R7 is C1-4 alkyl optionally substituted with OR8, halogen, CF3, NR5R6, or S(O)nR9where n is 0-2; each R8 is H or C1-4 alkyl optionally substituted with halogen or OH; and R9 is C1-4 alkyl; and the salts, solvates and hydrates thereof.
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Page/Page column 9
(2008/06/13)
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- Substituted alkanoic acids
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The invention is directed to physiologically active compounds of general formula (I): wherein:- represents (i) a saturated 3 to 6 membered carbocycle, optionally substituted by one or more alkyl groups, (ii) indanyl or (iii) a saturated 4 to 6 membered heterocyclic ring; R1 represents R3Z1-Het- or R4N(R5)—C(═O)—NH—Ar1—; L1 represents an —R6—R7— linkage; R2 represents hydrogen, halogen, lower alkyl or lower alkoxy; L2 represents an alkylene linkage; Y is carboxy or an acid bioisostere; and their corresponding N-oxides or prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their corresponding N-oxides or prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (α4β1).
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- Antibody-catalyzed hydrolysis of oligomeric esters: A model for the degradation of polymeric materials
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A catalytic antibody has been discovered that degrades oligomeric ester substrates.
- Bruemmer,Hoffman,Chen,Janda
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- AROMATIC AMINE DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND AGENTS CONTAINING THE SAME
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Compounds of a formula: wherein Ring A represents an optionally-substituted aromatic ring; Ring B represents an optionally-substituted cyclic hydrocarbon group; Z represents an optionally-substituted cyclic group; R1 represents a hydrogen atom, an optionally-substituted hydrocarbon group, an optionally-substituted heterocyclic group, or an acyl group; R2 represents an optionally-substituted amino group; D represents a chemical bond or a divalent group; E represents -CO-, -CON(Ra)-, COO-, -N(Ra)CON(Rb)-, -N(Ra)COO-, -N(Ra)SO2-, -N(Ra)-, -O-, -S-,-SO- or -SO2- (in which Ra and Rb each independently represent a hydrogen atom or an optionally-substituted hydrocarbon group); G represents a chemical bond or a divalent group; L represents (1) a chemical bond or (2) a divalent hydrocarbon group optionally having from 1 to 5 substituents selected from;(i) a C1-6 alkyl group,(ii) a halogeno-C1-6 alkyl group,(iii) a phenyl group,(iv) a benzyl group,(v) an optionally-substituted amino group,(vi) an optionally-substituted hydroxy group, and(vii) a carbamoyl or thiocarbamoyl group optionally substituted by: a C1-6 alkyl group, an optionally-substituted phenyl group, or an optionally-substituted heterocyclic group, and optionally interrupted by -O- or -S-; X represents an oxygen atom, an optionally-oxidized sulfur atom, an optionally-substituted nitrogen atom, or an optionally-substituted divalent hydrocarbon group; Y represents two hydrogen atoms, an oxygen atom or a sulfur atom; .... means that R2 may be bonded to the atom on Ring B to form a ring, or their salts, and a method for producing them.
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- Substituted benzene derivatives useful as neuraminidase inhibitors
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A compound of the Formula (I): STR1 or pharmaceutically-suitable salts or prodrug forms thereof, wherein: n is 0-1; m is 0; p is 0-1; R1 is --CO2 H; R2 is selected from the group consisting of H, --OH, and --NH2 ; R3 is H; R4 is --C(O)NHR8 ; R5 is --NHC(R6)NH2 R6 is selected from the group consisting of =NH, =NOH, =NCN, =O, and =S; and R8 is selected from the group consisting of C1 -C4 linear or branched alkyl substituted with 0-3 halogens on each carbon.
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- Immunomodulating agent
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Phenylacetic acid derivatives of the formula: STR1 wherein R1 is hydrogen or STR2 wherein R5 is an alkyl group of 1-6 carbon atoms or an aryl group; R2 and R3 are independently hydrogen or an alkyl group of 1-4 carbon atoms; R4 is hydrogen or an alkyl group of 1-4 carbon atoms, have been found to possess immunomodulating activity.
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- Antibody Catalysis Approaching the Activity of Enzymes
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Antibodies were raised to phosphonate esters that model a carboxyl esterolytic transition state.Twenty monoclonal antibodies were screened by a direct assay for hydrolysis of the carboxylic esters deduced from the structure of the transition-state analogue.Five of these were found to be esterases.The transition-state analogue is a specific inhibitor of the activity.One antibody accelerates the hydrolysis of a related substrate with kcat of 20 s-1 and Km of 1.5 mM at pH 8.0.This represents an acceleration of several million times above the spontaneous rate of hydrolysis.The kinetic constants for two substrates and the inhibition constant suggest the better binding of transition states than ground states to the antibody.The pH dependence of the activity can be explained by the titration of an amino acid side chain with a pKa of about 8.9.Activity is abolished by protein nitration that is specific for tyrosyl groups, and the nitration of two or more groups is prevented by the presence of the phosphonate ligand.Thus, the residues that constitute the combining site of the antibody may act analogously to residues in the active site of enzymes.These results demonstrate that an esterolytic antibody can be relatively efficient as compared with similar enzymes.
- Tramontano, Alfonso,Ammann, Adrian A.,Lerner, Richard A.
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p. 2282 - 2286
(2007/10/02)
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- Hydroxyalkylenimino-phenyl-acetic acids
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New α-(cyclic tert. aminophenyl)-aliphatic acids, e.g. those of the formula SPC1 R1 = h or alkyl R2 = h, alk(en)yl, cycloalk(en)- yl or cycloalk(en)yl-alkyl A = hydroxylated lower alkylene And functional derivatives thereof, are anti-inflammatory agents.
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- Tertiary aminoacids as anti-inflammatory agents
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New α-(cyclic tert. aminophenyl)-aliphatic acids, e.g. those of the formula SPC1 R1 = h or alkyl R2 = h, alk(en)yl, cycloalk(en)yl or cycloalk(en)yl-alkyl A = hydroxylated lower alkylene And functional derivatives thereof, are anti-inflammatory agents.
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