- Design, synthesis, and biological activity evaluation of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives as broad-spectrum antifungal agents
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To discover antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum antifungal activity against Candida albicans with MIC values in the range of 0.03–0.5 μg/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25–2 μg/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro, with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study.
- Zhao, Liyu,Sun, Yin,Yin, Wenbo,Tian, Linfeng,Sun, Nannan,Zheng, Yang,Zhang, Chu,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
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- Aminobenzoic acid derivatives as antioxidants and cholinesterase inhibitors; synthesis, biological evaluation and molecular docking studies
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Cholinesterase namely, acetyl- and butyrylcholinesterase (AChE and BChE, respectively), has been recognized as a primary class of enzyme that hydrolyzes the acetylcholine (ACh) neurotransmitter in synaptic junctions. Diminished levels of the neurotransmitter in synaptic junction lead to Alzheimerís disease (AD). Inhibition of cholinesterase is thus, an attractive strategy for AD treatment. The study includes the synthesis and characterization of a series of 2-, 3- and 4-aminobenzoic acid derivatives (1a?5c), their biological screening against cholinesterase enzyme and molecular docking study to demonstrate putative binding modes. Antioxidant potential of the synthesized series was also determined. The cholinesterase enzyme inhibition assay showed that compound 5b has the highest inhibition potential against acetylcholinesterase with an IC50 value of 1.66 ± 0.03 μM while in case of butyrylcholinesterase, compound 2c has the highest inhibitory potential with an IC50 value of 2.67 ± 0.05 μM. Molecular docking studies supports the results of enzyme inhibition potential with binding energy value ?G = -9.54 Kcal mol-1 for compound 5b in case for acetylcholinesterase while for butyrylcholinesterase, ?G = -5.53 Kcal mol-1 was obtained for compound 2c. The synthesized series of compounds also shows mild to moderate antioxidant potential. The benzoyl- containing compounds shows better antioxidant activity as compared to other derivatives of the synthesized series. Based on the molecular docking studies and enzyme inhibition potential, the synthesized series of compounds can be regarded as potent cholinesterase inhibitors and can be used for designing and synthesizing more potent drugs for Alzheimerís disease and neurodegenerative diseases.
- Iftikhar, Kiran,Murtaza, Shahzad,Kousar, Naghmana,Abbas, Aadil,Tahir, Muhammad Nawaz
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p. 385 - 396
(2018/04/23)
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- Substituted pyridoimidazole derivative and preparation thereof, and applications of substituted pyridoimidazole derivative in medicines
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The present invention discloses a substituted pyridoimidazole derivative and preparation thereof, and applications of the substituted pyridoimidazole derivative in medicines, and particularly relates to a new derivative represented by a general formula (I) and a pharmaceutically acceptable salt thereof or a pharmaceutical composition containing the new derivative, and a preparation method of the new derivative. The present invention further discloses applications of the derivative and the pharmaceutically acceptable salt thereof or the pharmaceutical composition containing the new derivative in Bruton tyrosine kinase inhibitors and in preparation of drugs for treatment and/or prevention of tumors, inflammations, and other diseases, wherein each substituent in the general formula (I) is defined in the specification. The formula (I) is defined in the specification.
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- With substituted pyrazine and imidazole derivatives, their preparation and their use in medicine (by machine translation)
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The invention discloses a substituted pyrazine and imidazole derivatives, their preparation and their use in medicine. Specifically, the invention relates to a compound of general formula (I) indicated by the new derivative and its pharmaceutically acceptable salt or pharmaceutical composition containing the same, and its preparation method. The invention also discloses the derivative and its pharmaceutically acceptable salt or pharmaceutical composition containing the same in the Bruton tyrosine kinase inhibitors, and in preparing and treating and/or preventing tumor diseases such as inflammation of the application of the medicament. Wherein the general formula (I) of each substituent as defined in the specification. (by machine translation)
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- Derivative with imidazopyridine, preparation method and application in medicine thereof
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The invention discloses a derivative with imidazopyridine, a preparation method and application in medicine thereof. Concretely speaking, the invention relates to a novel derivative, medicinal salt of the derivative or pharmaceutical compositions containing the derivative, and the preparation method of the derivative showed in general formula (I). The invention also discloses application of the derivative, medicinal salt of the derivative or pharmaceutical compositions containing the derivative in Bruton tyrosine kinase inhibitor, preparing the medicine for treating or preventing tumor and inflammation diseases. Substituent groups in general formula (I) are identical to definitions in the specification (the structure is shown in the description).
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- Derivative having imidazopyrazines, preparation method and application thereof of derivative on medicine
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The invention discloses a derivative having imidazopyrazines, a preparation method and an application thereof of the derivative on medicine. Concretely speaking, the invention relates to a novel derivative shown in a general formula (I) and its medicinal salt or a pharmaceutical composition containing the derivative, and its preparation method. The invention also discloses the derivative or its medicinal salt or an application of the pharmaceutical composition containing the derivative in a Bruton tyrosine kinase inhibitor, and in preparation of medicines for treating and/or preventing diseases such as tumour and inflammation. The substituent in the formula (I) has same definition in the specification.
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- Catalyst-Free Singlet Oxygen-Promoted Decarboxylative Amidation of α-Keto Acids with Free Amines
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A novel catalyst-free decarboxylative amidation of α-keto acids with amines under mild conditions has been developed. Advantages of the new protocol include avoidance of metal catalysts and high levels of functional group tolerance. In addition, the reaction can be scaled up and shows high chemoselectivity. Preliminary mechanistic studies suggest that singlet oxygen, generated from oxygen under irradiation, is the key promoter for this catalyst-free transformation.
- Xu, Wen-Tao,Huang, Bei,Dai, Jian-Jun,Xu, Jun,Xu, Hua-Jian
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supporting information
p. 3114 - 3117
(2016/07/14)
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- Thermoplastic polymer composition
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The invention provides a compound conforming to the structure of Formula (C) The invention also provides a thermoplastic polymer composition comprising a polyolefin polymer and a compound conforming to the structure of Formula (C) as a nucleating agent.
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Page/Page column 50
(2015/12/17)
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- 2-(HETERO)ARYL-BENZIMIDAZOLE AND IMIDAZOPYRIDINE DERIVATIVES AS INHIBITORS OF ASPARAGIME EMETHYL TRANSFERASE
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Substituted benzimidazole and 3H-imidazo[4,5-b]pyridines or formula I: where X and Y respectively are selected from: (i) N and N; and (ii) N and CR4; A2 is selected from:, a C5 heteroarylene group, containing 2 or 3 ring heteroatoms, where the bonds to L1 and the core are β to one another; L1 is selected from: (i)A1-O-CH2-A2; (ii)A1-CH2-O-A2; (iii)A1-C(=O)-NH-A2; (iv)A1-CH(OH)-A2; (v)A1-CH2-NH-C(=O)-A2; (vi) A1-S-CH2-A2; (vii)A1- CH2-S-A2; (viii)A1-CH2-A2; and (ix)A1-CH(CH3)-O-A2; A1 is phenyl, optionally substituted by F or CF3; their use as pharmaceuticals, and in particular, in treating cancer and hemoglobinopathies.
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- Substituent effects on energetics of peptide-carboxylate hydrogen bonds as studied by 1H NMR spectroscopy: Implications for enzyme catalysis
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Substituent effects in N-H···O hydrogen bonds were estimated by comparing the acidities of two series of model compounds: N-benzoylanthranilic acids (A) and 4-benzoylamidobenzoic acids (B). Intramolecular N-H···O hydrogen bonds were found to be present in the A series of compounds, while B acids were used as control models. The respective pKa values for A and B acids were determined experimentally in DMSO solution using proton NMR spectroscopy. With X = H, the pKa for A and B acids were observed to be 7.6 and 11.6, respectively, a difference of 4.0 units (ΔpKa). However, with X = p-NO 2, the ΔpKa value between A and B acids increased to 4.7 units: the pKa values for A and B acids were determined as 6.7 and 11.4, respectively. The ΔpKa values between A and B acids as a function of the X substituents were studied in 10 other examples. The effects of X substituents in A acids could be predicted on the basis of the observed linear Hammett correlations, and the sensitivity of each substituent effect was found to be comparable to those observed for the ionization of substituted benzoic acids (ρ = 1.04 for A acids, and ρ = 1.00 for benzoic acids).
- Emenike, Bright U.,Liu, Albert Tianxiang,Naveo, Elsy P.,Roberts, John D.
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p. 11765 - 11771
(2014/01/06)
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- Design, synthesis, and activity evaluation of broad-spectrum small-molecule inhibitors of anti-apoptotic Bcl-2 family proteins: Characteristics of broad-spectrum protein binding and its effects on anti-tumor activity
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On the basis of the comparison of the structure of the Bim BH3: Bcl-x L complex and that of the ABT-737: Bcl-xL complex, a series of class A compounds were designed. These compounds had the basic skeleton of ABT-737 and the h2 residues of Bim BH3. These residues had shown themselves to be relevant to Bim BH3's broad-spectrum binding properties in saturation mutagenesis assays. Unlike ABT-737, which is a selective inhibitor of anti-apoptotic members of the Bcl-2 protein family, the class A compounds showed broad-spectrum binding activity to target proteins similar to those of Bim BH3 peptide. Then class B compounds were synthesized by modifying the structure of the most effective class A compound, A-4. Most of these class B compounds showed better binding affinity to the target proteins than the class A compounds had. They also showed themselves more effective than ABT-737 at inhibiting growth in multiple tumor cell lines known to express Bcl-x L, Bcl-2, and Mcl-1 proteins at high levels. Compounds B-11 and B-12 had the strongest anti-tumor activity of any compounds we produced. This study suggests that it is feasible to design small-molecule inhibitors based on the structure of Bim BH3, which shows broad-spectrum binding to Bcl-xL, Bcl-2, and Mcl-1 proteins. Our results also suggest that the broad-spectrum properties of small-molecule inhibitors binding to target proteins play a critical role in inhibiting the growth of many tumor cells. Finally, our study provides a series of lead compounds that merit further research into anti-cancer therapeutics.
- Zheng, Can-Hui,Yang, Hui,Zhang, Meng,Lu, Shi-Hai,Shi, Duo,Wang, Juan,Chen, Xiu-Hua,Ren, Xiao-Hui,Liu, Jia,Lv, Jia-Guo,Zhu, Ju,Zhou, You-Jun
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- Design and synthesis of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors
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Monoamine oxidase-B (MAO-B) inhibitor has been used as neuroprotectants to treat the motor deficits of Parkinson's disease (PD). We designed and synthesized a class of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors. The compounds have various inhibitory effects, with compound 6a having a Ki value of 0.26 lM. Their promising activity in vitro suggests potential use in the treatment of PD.
- Song, Bo,Xiao, Tong,Qi, Xiaolu,Li, Ling-Na,Qin, Kuiyou,Nian, Siyun,Hu, Guo-Xin,Yu, Yinfei,Liang, Guang,Ye, Faqing
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experimental part
p. 1739 - 1742
(2012/04/04)
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- Brine-mediated efficient benzoylation of primary amines and amino acids
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Benzoylation of primary amines and amino acids is efficiently carried out in a brine solution using a stoichiometric amount of benzoyl chloride followed by trituration with aqueous saturated bicarbonate solution. Copyright Taylor & Francis Group, LLC.
- Chattopadhyay, Gautam,Chakraborty, Suchandra,Saha, Chandan
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experimental part
p. 4068 - 4075
(2009/04/11)
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- Efficient amidation from carboxylic acids and azides via selenocarboxylates: Application to the coupling of amino acids and peptides with azides
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(Chemical Equation Presented) A facile one-pot procedure for the coupling of carboxylic acid and azide via selenocarboxylate and selenatriazoline has been developed and successfully applied to the coupling of amino acids and peptides with azides. Selenocarboxylates are readily prepared by the reaction of the activated carboxylic acids with LiAlHSeH under mild conditions. The Selenocarboxylates formed in situ are used to react directly with azides to form the corresponding amides via a selenatriazoline intermediate. Excellent yields were obtained for electron-deficient azides, and moderate to good yields were obtained for electron-rich azides. The selenocarboxylate/azide amidation reaction is clean and chemoselective. It provides an attractive alternative method to the conventional acylation of amines when an amide bond needs to be formed without going through an amine intermediate.
- Wu, Xinghua,Hu, Longqin
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p. 765 - 774
(2007/10/03)
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- Improved solubility and stability of trialkylammonium selenocarboxylate in organic solvents for efficient amidation with azides
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Trialkylammonium selenocarboxylate, formed in situ from the reaction of diacyl diselenide with piperidine in the presence of diisopropylethylamine, was found to react readily at room temperature with electron-deficient azides to form amides in excellent yields. The trialkylammonium selenocarboxylate salt formed has good solubility and stability in organic solvents. The enhanced stability allowed mild heating to improve the amidation yields with electron-rich azides.
- Surabhi, Prathima,Wu, Xinghua,Hu, Longqin
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p. 4609 - 4613
(2007/10/03)
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- HYDROXAMIC ACID DERIVATIVES AND THE METHOD FOR PREPARING THEREOF
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The present invention provides hydroxamic acid derivatives represented by the following formula (I), having anti-aging efficacy and a method for preparation thereof: wherein, R1 is or, herein, R5 and R6 each independently
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Page/Page column 13-15
(2010/02/11)
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- Amide bond formation from selenocarboxylates and aromatic azides
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A new method of amide bond formation was developed through the reaction of potassium selenocarboxylates with aromatic azides at room temperature. Potassium selenocarboxylates were prepared in situ by the treatment of diacyl selenides with potassium methoxide at 5°C under N2. After the addition of azide, the reaction was allowed to gradually warm to room temperature and was stirred for 0.5-2 h. Excellent yields were obtained when electron deficient aromatic azides were used.
- Wu, Xinghua,Hu, Longqin
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p. 8401 - 8405
(2007/10/03)
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- 3,6-Dibenzoxyl-1,2-pyridazine: A new versatile benzoyl transferring agent for NH2, -OH and -SH benzoylations
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A newly synthesized 3,6-dibenzoxyl-1,2-pyridazine 3 has been investigated for its potential to transfer the benzoyl group to various organic substrates carrying -NH2, -OH and -SH groups. The benzoyl transfer is fairly general in scope, occurs under convenient conditions and provides good to excellent yields of benzoylated products. Moreover, by choosing proper conditions, it is possible to achieve chemoselective benzoylation in bi-functional molecules. For instance, N-benzoylation of aromatic amines can be selectively accomplished over that of aliphatic amines and vice versa by manipulating reaction conditions. Selective N- or O-benzoylation in aminophenols is also possible. Although, not studied in detail, we final that dibenzoate 3 can also be used to effect C-benzoylation of reactive phenols and ketones, as exemplified by the C-benzoylation of resorcinol and acetophenone, respectively. Dibenzoate 3, besides being a crystalline, easy to handle, solid possesses twice the potential as an acyl carrier compared to the other known acyl carriers. These features make 3 as an attractive choice for many applications pertaining to benzoyl transfer reactions.
- Mashraqui, Sabir Hussain,Shivaji, Jadhav Latika
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p. 927 - 935
(2007/10/03)
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- Acyl maleic hydrazides as versatile acyl transferring agents
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Acyl maleic hydrazides have been found to act as effective acyl transferring agents to substrates containing heteroatom nucleophiles such as amines, phenols, alcohols and thiols under mild and convenient conditions.
- Mashraqui, Sabir H.,Shivaji, Jadhav L.
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p. 121 - 123
(2007/10/03)
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- 1,3,4-Oxadiazolethiol as Acyl-transfer Reagent in Acylation of Amines: A One-pot Reaction
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Amines are acylated using 5-(2,4-dichlorophenyl)-1,3,4-oxadiazolethiol in the presence of diethyl chlorothiophosphate (DCTP) in good yield.
- Goswami,Borthakur,Ghosh
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p. 268 - 269
(2007/10/03)
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- Method for lowering plasma levels of lipoprotein (a)
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Retinoids are effective to lower plasma levels of Lp (a) in mammals.
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- A consideration of various ionic forms of amino acids in evaluating the rate constant of N-acylation
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The concentrations of ionic forms of p- and m-aminobenzoic acids in water and water-dioxane solvents of variable composition were calculated at various pH values. Based on the results of the calculations and on the kinetic data obtained previously, the ra
- Kuritsyn,Kalinina
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p. 2004 - 2006
(2007/10/03)
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- Water-Soluble Acylating Agents: Preparation of 2-Acylthio-1-alkylpyridinium Salts and Acylation of Phenols, Acids, and/or Amines with These Salts in an Aqueous Phase
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Reaction of phenols, amines, and acids with 2-benzoylthio-1-methylpyridinium chloride prepared in situ from benzoyl chloride and 1-methyl-2(1H)-pyridinethione, afforded the corresponding benzoyl derivatives in good yields.In the reaction of p-nitrophenol, even catalytic amount of 1-methyl-2(1H)-pyridinethione proved to be effective.Similar reactions of p-nitrophenol with isobutyryl chloride and acetyl chloride in the presence of 1-methyl-2(1H)-pyridinethione afforded p-nitrophenyl isobutyrate and p-nitrophenyl acetate in 63 and 44percent yields, respectively. 2-Benzoylthio-, 2-acetylthio-, and 2-isobutyrylthio-1-ethylpyridinium tetrafluorobora tes were prepared by treatment of the corresponding 2-acylthiopyridines with triethyloxonium tetrafluoroborate.These pyridinium salts also acted as acylating agents in an aqueous phase. some competitive reactions of 2-aminoethanol and phenols with 2-benzoylthio-1-methylpyridinium chloride were also investigated.
- Sakakibara, Tohru,Watabe, Yukie,Yamada, Masahide,Sudoh, Rokuro
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p. 247 - 254
(2007/10/02)
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- Stereoelectronic factors influencing the biological activity and DNA interaction of synthetic antitumor agents modeled on CC-1065
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The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effectiv
- Warpehoski,Gebhard,Kelly,Krueger,Li,McGovren,Prairie,Wicnienski,Wierenga
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p. 590 - 603
(2007/10/02)
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- KINETICS OF ACYLATION OF ANILINES MONOSUBSTITUTED IN THE RING BY BENZOYL CHLORIDE IN N,N-DIMETHYLACETAMIDE
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The kinetics of the acylation of meta- and para-substituted primary arylamines by benzoyl chloride in N,N-dimethylacetamide was studied.The sensitivity of the reaction to changes in the structure of the arylamine in N,N-dimethylacetamide is lower than in other organic solvents.A mechanism involving catalysis of the acylation reaction by the solvent molecules is proposed.
- Kuz'min, N. I.,Kabanova, N. I.,Zhizdyuk, B. I.,Chegolya, A. S.
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p. 2139 - 2141
(2007/10/02)
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