- Convenient method for the synthesis of some novel chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives and biological evaluation of their antioxidant, cytotoxic, and molecular docking properties
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Ten chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives 6a-6j have been synthesized from optically pure amino methyl phenol 5 and 4-nitrophenyl chloroformate. These derivatives 6a-6j are characterized by 1H NMR, 13C NMR, FT-IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a-6j were screened for their in vitro antioxidant activity. Among the compounds 6b-d and 6h-j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e-g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC50 value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b, 6h, and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC50 value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT-3 (PDB ID: 1BG1) and BCL-2 (PDB ID: 4AQ3) proteins against the four active compounds 6b, 6h, 6i, and 6j. The binding energies of the tested compounds were in the range of ?7.76 to ?8.41 kcal/mol, which is very close to doxorubicin (?8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.
- Matam, Sivakumar,Kaliyan, Prabakaran,Selvaraj, Loganathan,Muthu, Seenivasa Perumal,Lohanathan, Bharathi Priya,Viswanadhan, Vijaya Padma,Makala, Himesh,Venkatasubramanian, Ulaganathan
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supporting information
p. 569 - 579
(2020/12/11)
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- Preparation method of phosphodiesterase inhibitor
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The invention discloses a preparation method of a phosphodiesterase inhibitor and belongs to the field of medicinal chemistry. The preparation method comprises the following steps: starting the raw material 1 and methanol to prepare the intermediate I without adding organic solvent crystallization. After the series of centrifugation, washing and drying, the intermediate II is directly condensed and cyclized with piperonal, and a final product tadalafil is prepared by chloroacetylation, aminolysis and refining steps. The method improves the product yield and quality, greatly shortens the reaction period, reduces the operation steps and the production cost, and is suitable for industrial mass production.
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Paragraph 0016; 0026-0040
(2021/11/03)
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- Lithocholic acid-tryptophan conjugate (UniPR126) based mixed micelle as a nano carrier for specific delivery of niclosamide to prostate cancer via EphA2 receptor
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Targeted delivery of chemotherapeutic agents is considered a prominent strategy for the treatment of cancer due to its site-specific delivery, augmented penetration, bioavailability, and improved therapeutic efficiency. In the present study, we employed UniPR126 as a carrier in a mixed nanomicellar delivery system to target and deliver anticancer drug NIC specifically to cancer cells via EphA2 receptors as these receptors are overexpressed in cancer cells but not in normal cells. The specificity of the carrier was confirmed from the significant enhancement in the uptake of coumarin-6 loaded mixed nanomicelle by EphA2 highly expressed PC-3 cells compared to EphA2 low expressed H4 cells. Further, niclosamide-loaded lithocholic acid tryptophan conjugate-based mixed nanomicelle has shown significant synergistic cytotoxicity in PC-3 but not in H4 cells. In vivo anticancer efficacy data in PC-3 xenograft revealed a significant reduction in the tumor volume (66.87%) with niclosamide-loaded lithocholic acid tryptophan conjugate nanomicelle, where pure niclosamide showed just half of the activity. Molecular signaling data by western blotting also indicated that niclosamide-loaded lithocholic acid tryptophan conjugate nanomicelle interfered with the EphA2 receptor signaling and inhibition of the Wnt/beta-catenin pathway and resulted in the synergistic anticancer activity compared to niclosamide pure drug.
- Jannu, Arun Kumar,Puppala, Eswara Rao,Gawali, Basveshwar,Syamprasad,Alexander, Amit,Marepally, Srujan,Chella, Naveen,Gangasani, Jagadeesh Kumar,Naidu
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- Translation of Mycobacterium Survival Strategy to Develop a Lipo-peptide based Fusion Inhibitor**
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The entry of enveloped virus requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad-spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome–lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40-repeat protein suggest that the trp-asp (WD) sequence is placed at distorted β-meander motif (more exposed) in coronin 1. The unique structural feature of coronin 1 was explored to identify a simple lipo-peptide sequence (myr-WD), which effectively inhibits membrane fusion by modulating the interfacial order, water penetration, and surface potential. The mycobacterium inspired lipo-dipeptide was successfully tested to combat type 1 influenza virus (H1N1) and murine coronavirus infections as a potential broad-spectrum antiviral agent.
- Sardar, Avijit,Lahiri, Aritraa,Kamble, Mithila,Mallick, Amirul I.,Tarafdar, Pradip K.
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supporting information
p. 6101 - 6106
(2021/02/01)
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- A fast and direct iodide-catalyzed oxidative 2-selenylation of tryptophan
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A metal-free 2-selenylation of tryptophan derivatives is reported, where the use of iodide as the catalyst and oxone as the oxidant is key to obtain high yields. Various functional groups within the di-seleny and the indole ring are tolerated, and no racemization is generally observed.
- Gao, Yu-Ting,Liu, Shao-Dong,Cheng, Liang,Liu, Li
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supporting information
p. 3504 - 3507
(2021/04/12)
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- Ribose conversion with amino acids into pyrraline platform chemicals-expeditious synthesis of diverse pyrrole-fused alkaloid compounds
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One-pot conversion of sustainable d-ribose with l-amino acid, methyl esters produced pyrrole-2-carbaldehydes 5 in reasonable yields (32-63%) under pressurized conditions of 2.5 atm at 80 °C. The value-added pyrraline compounds 5 as platform chemicals were utilized for quick installation of poly-heterocyclic cores for the development of pyrrole-motif natural and artificial therapeutic agents. A pyrrole-fused piperazin-2-one scaffold 6 was prepared by reductive amination of pyrralines 5 with benzylamine. While further cyclization of pyrralines 5 with ethane-1,2-diamine produced pyrrolo-piperazin-2-ones 7 with an extra imidazolidine ring, the reaction with 2-amino alcohols derived from natural l-amino acids, alanine, valine, and phenylalanine, respectively provided pyrrolo-piperazin-2-ones 8, 9, and 10 with oxazolidine as the third structural core. Cell viability and an anti-inflammatory effect of the synthesized compounds were briefly tested by the MTT method and the Griess assay, among which 8h and 10g exhibited significant anti-inflammatory effects with negligible cell toxicity.
- Cho, Soohyeon,Gu, Lina,In, Ik Joon,Kim, Hakwon,Koo, Sangho,Lee, Taehoon,Wu, Bo
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p. 31511 - 31525
(2021/11/30)
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- (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative as well as preparation method and application thereof
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The invention discloses a (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative shown as a formula (I) or an optical isomer, a diastereomer and racemate mixture and pharmaceutically acceptable salt thereof as well as a preparation method and application of the (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative. It is shown by comparison of results of a positive control group and a model group on lymphedema prevention experiments that the compound disclosed in the invention shows obvious anti-edema activity.
- -
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Paragraph 0047; 0124-0128
(2021/02/10)
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- Synthesis and anti-tumor activity of marine alkaloids
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Marine alkaloids were divided into five categories from the perspective of anti-tumor activity. The optimization process, chemical synthesis, anti-tumor activity evaluation and structure–activity relationship of various compounds were discussed.
- Chen, Guangying,Huang, Gangliang,Zhou, Shiyang
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- Pentacyclic indole quinolizine with inhibiting cell autophagy and synthesis method thereof as, well, as anti-tumor activity and application thereof
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The invention discloses pentacyclic indole quinolizine inhibiting cell autophagy, i.e. (6S)-3-acetyl-6-(N-phenylacetylaminoacyl)-methyl oxide-4, 6, 7, 12-tetrahydro-4-oxoindole[2, 3-a]quinolizine, and also discloses synthesis, activity and application of the compound.
- -
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Paragraph 0017; 0020-0021
(2020/01/30)
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- Design, synthesis and bio-evaluation of C-1 alkylated tetrahydro-β-carboline derivatives as novel antifungal lead compounds
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The field of antifungal agent has become static and development of resistance by the pathogen as well as limited clinical efficacy of marketed drugs demand the constant development of new antifungals. The presence of hydrocarbon chain of specific length linked with various different heterocycles was found to be an important structural feature in various antifungal lead compounds. Based on the prominent antimicrobial activity of β-carboline derivatives, a set of C1 alkylated tetrahydro-β-carboline derivatives were proposed to be active against fungi. To validate and confirm the role of suitable alkyl chains linked to a β-carboline scaffold, few related analogues having C1 aryl substituents were also synthesized in one step via classic Pictet-Spengler reaction. The synthesized library was evaluated for its antifungal activity against C. albicans, C. krusei, C. parapsilosis, C. kefyr, C. glabrata, C. tropicalis and C. neoformans. One of the library members (compound 12c), with n-alkyl chain of eight carbons exhibited potent antifungal activity against C. glabrata and C. kefyr. The lead compound, being selectively toxic also demonstrated prominent synergy enhancing the potency of antifungal drugs up to 10-fold. The time kill kinetic studies confirmed the efficacy of compound 12c, where the results obtained were comparable to that of Amp B. FE-SEM analysis revealed the increased asymmetry, disintegration and roughness of cell surface which could be because of the possible interaction of compound 12c at membrane level or interference in cell wall structure. Apoptosis/necrosis detection assay confirmed the significant apoptotic activity in C. glabrata cells after 12c treatment which was responsible for the rapid killing of C. glabrata cells.
- Singh, Rahul,Jaisingh, Aanchal,Maurya, Indresh K.,Salunke, Deepak B.
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supporting information
(2019/12/27)
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- Carboline derivative/analogue as well as preparation method and application thereof
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The invention belongs to the field of chemical medicines, and provides a compound shown as a formula I or pharmaceutically acceptable salt thereof. The invention also provides analogues of the compound as shown in the formula I in the specification. Biological experiments show that the compound disclosed by the invention has anti-tumor activity and serves as a good tubulin inhibitor; the compound91b has excellent antitumor activity, can effectively promote degradation of tubulin; drug resistance caused by overexpression of beta-tubulin III and P-gp can be eliminated, and a new choice is provided for clinical medication.
- -
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Paragraph 0063-0066
(2020/07/13)
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- Nano cuboids: Impact of 8-hydroxyquinoline on tryptophan properties and its applications
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N-terminal tryptophan residues can be labeled with fluorophore by chemical reaction. Here in we report conjugation of 8-hydroxyquinoline (as fluorophore) with tryptophan using Schiff-base condensation reaction to decipher the impact of 8-hydroxyquinoline on the fluorescence and self-assembly properties of tryptophan in water. This water-soluble hydroxyquinoline–tryptophan (HQ-W1) conjugate has been demonstrated to have Aggregation Induced Emission (AIE) phenomena in water. HQ-W1 undergo spontaneous self-assembly to form nano cuboidal superstructures having 200–500 nm diameter and 300–650 nm length. In metal-ion binding studies this HQ-W1 shows selective fluorescence enhancement (14.5-fold) in the presence of Al3+ ions. The detection limit is 3.0 nM (UV method) and 3.53 nM (FI method). The AIE utility of HQ-W1 has been demonstrated by developing latent fingerprints.
- Sharma, Poonam,Singh, Prabhpreet
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supporting information
(2020/02/13)
-
- Cu-Catalyzed Site-Selective C(sp2)-H Radical Trifluoromethylation of Tryptophan-Containing Peptides
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Site-selective functionalization of C-H bonds within a peptide framework poses a challenging task of paramount synthetic relevance. Herein, we report an operationally simple C(sp2)-H trifluoromethylation of tryptophan (Trp)-containing peptides. This fluorination technique is characterized by its chirality preservation, tolerance of functional groups, and scalability and exhibits chemoselectivity for Trp residues over other amino acid and heterocyclic units. As a result, it represents a sustainable tool toward the late-stage peptide modification and protein engineering.
- Correa, Arkaitz,Guerrero, Itziar
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supporting information
p. 1754 - 1759
(2020/03/23)
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- Solvent free three-component synthesis of 2,4,5-trisubstituted-1H-pyrrol-3-ol-type Compounds from L-tryptophan: DFT-B3LYP calculations for the reaction mechanism and 3H-pyrrol-3-one?1H-pyrrol-3-ol tautomeric equilibrium
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In this paper, we describe the solvent-free three-component synthesis of 2,4,5-trisubstituted-1H-pyrrol-3-ol-type compounds from L-tryptophan. The first step of the synthetic methodology involved the esterification of L-tryptophan in excellent yields (93–98%). Equimolar mixtures of alkyl 2-aminoesters, 1,3-dicarbonyl compounds, and potassium hydroxide (0.1 eq.) were heated under solvent-free conditions. The title compounds were obtained in moderate to good yields (45%–81%). Density functional theory using “Becke, 3-parameter, Lee–Yang–Parr” correlational functional (DFT-B3LYP) calculations were performed to understand the molecular stability of the synthesized compounds and the tautomeric equilibrium from 3H-pyrrol-3-one type intermediates to 1H-pyrrol-3-ol type aromatized rings.
- Becerra, Lili Dahiana,Coy-Barrera, Ericsson,Quiroga, Diego
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- Synthesis and antimalarial activity of (S)-methyl-(7-chloroquinolin-4-ylthio)acetamidoalquilate derivatives
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The synthesis of five new (S)-methyl-(7-chloroquinolin-4-ylthio)acetamidoalquilate derivatives is carried out under a modified version of the Steglich esterification reaction between different l-amino acid methyl esters and 2-(7-chloroquinolin-4-ylthio)acetic acid. Two of the compounds showed significant inhibition (>50%) of β-hematin formation. The two active structures were tested in vivo as potential antimalarials in mice infected with Plasmodium berghei ANKA, a chloroquine susceptible strain. Compounds 6b and 6e exhibited antimalarial activity comparable to that of chloroquine.
- Colmenarez, Custodiana,Acosta, María,Rodríguez, Miguel,Charris, Jaime
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p. 161 - 166
(2020/01/09)
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- Enhancement of the chiroptical response of α-amino acids via N-substitution for molecular structure determination using vibrational circular dichroism
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The chiroptical response in the form of vibrational circular dichroism (VCD) in the midinfrared region is found to be enhanced when a hydrogen of amino group of l-tryptophan is substituted with acetyl, acryloyl, or maleyl group. The order of preference for VCD enhancement is found to be acryloyl > acetyl > maleyl group. The resulting experimental VCD spectra are also found to be satisfactorily reproduced by the quantum mechanical (QM) predicted spectra. The QM predicted spectra were simulated using the conformer populations, (a) predicted by Gibbs energies and (b) optimized to maximize the similarity between experimental and predicted VCD spectra. It is found that the conformer populations predicted by Gibbs energies do not yield the maximum possible similarity between experimental and the QM predicted spectra. This work identifies the N-substitution of α-amino acids and determining the conformer populations that best reproduce the experimental spectra as two new approaches for molecular structure determination.
- Polavarapu, Prasad L.,Santoro, Ernesto,Covington, Cody L.,Raghavan, Vijay
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supporting information
p. 564 - 578
(2020/03/13)
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- Preparation method of tryptophan ester hydrochloride
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The invention discloses a preparation method of tryptophan ester hydrochloride. The preparation method comprises the following steps: 1) reacting p-toluenesulfonyl chloride with tryptophan in alcoholto obtain a tryptophan ester hydrochloride crude product; and 2) purifying the crude product to obtain the tryptophan ester hydrochloride. According to the method, the p-toluenesulfonyl chloride and the lower alcohol which are available in the market and low in price are used as raw materials, reaction conditions are easy to implement, operation is easy, the cost is greatly reduced compared with other methods, the obtained product is high in purity and the method is suitable for large-scale industrial production.
- -
-
Paragraph 0041-0044
(2019/12/02)
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- Rhodium-Catalyzed Enantioselective Synthesis of Oxazinones via an Asymmetric Ring Opening-Lactonization Cascade of Oxabicyclic Alkenes
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The rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes is shown to be an efficient method for synthesizing chiral heterocycles. We demonstrate that the pairwise combination of chiral catalyst with chiral amino-acid-derived pronucleophiles results in a stereodivergent synthesis of diastereomeric hydroxyesters. A favorable conformational preference induces the subsequent lactonization of one diastereomer leading to the highly enantioselective synthesis of oxazinones.
- Yen, Andy,Pham, Anh Hoang,Larin, Egor M.,Lautens, Mark
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supporting information
p. 7549 - 7553
(2019/10/02)
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- Synthesis of Spiro-Pyrrolidinyloxindoles by Oxidative Rearrangement of N-Acyltetrahydro-β-carbolines Using an Oxone/Aqueous Acetone Mixture
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Spiro-pyrrolidinyl-2-oxindoles were prepared by the oxidative rearrangement of Na-acetyl-1,2,3,4-tetrahydro-β-carbolines (THBC) using dimethyldioxirane generated in situ. The Na-acetyl THBC substrates were obtained by Pictet-Spengler and acyl-Pictet-Spengler reactions of L-tryptophan methyl ester, followed by Na-acetylation. The stereoselectivity of the oxidative rearrangement was evaluated and 2D nuclear magnetic resonance (NMR) was used to determine the stereochemistry of the oxindole products relative to L-tryptophan. Density functional theory calculations were consistent with a face selective, substrate controlled, epoxidation of the indolic double bond. The calculations indicated that the resulting epoxide would readily rearrange at room temperature via a concerted ring opening/ring contraction process to give the 3-substituted-2-oxindole.
- Mar?al, Luisa L.,Garden, Simon J.
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- Access to Benzazepinones by Pd-Catalyzed Remote C-H Carbonylation of γ-Arylpropylamine Derivatives
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A general method for the construction of seven-membered rings through Pd-catalyzed C(sp2)-H carbonylation at the remote ?-position of γ-arylpropylamine derivatives, including chiral α-amino acids, has been developed using Mo(CO)6 as the CO source, furnishing richly functionalized benzo[c]azepin-1-one derivatives. The readily removable N-SO2Py protecting/directing group provides high levels of chemo-, regio- and diastereoselectivity. Furthermore, this method is amenable to the postsynthetic modification of complex molecules such as small peptides.
- Martínez-Mingo, Mario,Rodríguez, Nuria,Gómez Arrayás, Ramón,Carretero, Juan C.
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supporting information
p. 4345 - 4349
(2019/06/14)
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- 2,3,4,9-tetrahydro-1H-pyridino-[3,4-b]-indole compound and application thereof
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The invention belongs to the technical field of medicine, and relates to a 2,3,4,9-tetrahydro-1H-pyridino-[3,4-b]-indole compound and application thereof, in particular to a series of methyl 1-aryl-2-(aryl-formamyl)-2,3,4,9-tetrahydro-1H-pyridino-[3,4-b]-indole-3-carboxylate compounds, and an optical activator or racemate thereof or a pharmaceutically-acceptable salt, hydrate or solvate thereof. The invention further relates to application of the compound to the preparation of medicaments for treating and/or preventing cancers and other hyperplastic diseases. The structures of the compound andthe optical activator or racemate thereof or the pharmaceutically-acceptable salt, hydrate or solvent thereof are shown as a general formula I, wherein Ar1 and Ar2 are described in the claims and description. The general formula I is shown in the description.
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Paragraph 0084-0088
(2019/03/25)
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- Hydroxyphosphinylacetic acid as a chiral auxiliary compound
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The aim of the presented research was to check whether 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid is a versatile chiral phosphonic auxiliary (readily seen in 31P NMR). The preliminary studies indicate that this compound may be used as chiral derivatizing agents for amines and alcohols, since the separation of selected examples of diastereomeric alcohols and amines in 31P NMR spectra was found to be satisfactory. The preliminary research about using this compound as a CSA are also promising.
- Majewska, Paulina
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p. 585 - 590
(2019/01/04)
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- A transition metal-free approach towards synthesis of β-carboline tethered 1,3,4-oxadiazoles via oxidative C-O bond formation
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An efficient protocol has been developed for one-pot synthesis of biologically interesting β-carboline substituted 1,3,4-oxadiazoles via an I2-assisted oxidative C-O bond formation strategy. This metal-free sequential approach is found to be compatible with diversely substituted 1-formyl β-carbolines and aromatic as well as aliphatic hydrazides, providing access to a variety of multifunctional β-carboline linked 1,3,4-oxadiazole derivatives in good to excellent yields. The methodology was found to be applicable to gram scale synthesis of β-carboline substituted 1,3,4-oxadiazole derivatives. Additionally, β-carboline C1 linked 2-amino-1,3,4-oxadiazoles and bis-1,3,4-oxadiazoles were also synthesized using the same strategy.
- Singh, Dharmender,Tiwari, Sandip Kumar,Singh, Virender
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supporting information
p. 93 - 102
(2019/01/04)
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- Synthesis and structure-activity relationship of nitrile-based cruzain inhibitors incorporating a trifluoroethylamine-based P2 amide replacement
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The structure-activity relationship for nitrile-based cruzain inhibitors incorporating a P2 amide replacement based on trifluoroethylamine was explored by deconstruction of a published series of inhibitors. It was demonstrated that the P3 biphenyl substituent present in the published inhibitor structures could be truncated to phenyl with only a small loss of affinity. The effects of inverting the configuration of the P2 amide replacement and linking a benzyl substituent at P1 were observed to be strongly nonadditive. We show that plotting affinity against molecular size provides a means to visualize both the molecular size efficiency of structural transformations and the nonadditivity in the structure-activity relationship. We also show how the relationship between affinity and lipophilicity, measured by high-performance liquid chromatography with an immobilized artificial membrane stationary phase, may be used to normalize affinity with respect to lipophilicity.
- Gomes, Juliana C.,Cianni, Lorenzo,Ribeiro, Jean,dos Reis Rocho, Fernanda,da Costa Martins Silva, Samelyn,Batista, Pedro Henrique Jatai,Moraes, Carolina Borsoi,Franco, Caio Haddad,Freitas-Junior, Lucio H.G.,Kenny, Peter W.,Leit?o, Andrei,Burtoloso, Antonio C.B.,de Vita, Daniela,Montanari, Carlos A.
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-
- Synthesis of 2-D-L-tryptophan by sequential Ir-catalyzed reactions
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Herein, we report a practical synthesis of 2-D-l-tryptophan via sequential Ir-catalyzed C–H borylation, and Ir-catalyzed C-2-deborylative deuteration steps. In this synthetic sequence, deprotection of the Boc and methyl ester groups proved challenging, due to replacement of deuterium with hydrogen. However, mild deprotection conditions were developed to avoid this D/H scrambling. Further, 2-D-L-Tryptophan is stable in many buffers used for biological studies.
- Vallakati, Ravikrishna,Plotnikov, Abel T.,Altman, Ryan A.
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p. 2261 - 2264
(2019/03/04)
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- A concise synthesis of cyclobrassinin and its analogues via a thiyl radical aromatic substitution
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A simple and concise approach for the synthesis of cyclobrassinin has been developed through a thiyl radical-mediated intramolecular aromatic substitution, with benzoyl peroxide as an efficient initiator and oxidant. The current method can also be utilized in the synthesis of 6 and 7-membered ring cyclobrassinin analogues in moderate to good yields. The transformation involves a formal radical 6 and 7-endo-trig cyclization of the corresponding dithiocarbamate derivatives, which were generated from indole-3-methanamines and tryptophan.
- Zhong, Xin,Chen, Ning,Xu, Jiaxi
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supporting information
p. 13549 - 13557
(2018/08/21)
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- Tryptophan ester hydrochloride preparation method
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The invention discloses a synthesizing method for tryptophan ester hydrochloride. The synthesizing method includes the steps that firstly, organic amine serves as catalysts, in proper solvents, tryptophan and hydrogen chloride generate tryptophan hydrochloride; secondly, the tryptophan hydrochloride and ester are esterified at the backflow temperature, generated water is taken away in an azeotropy mode, an esterification reaction is promoted, and after the reaction is completed, the tryptophan ester hydrochloride as the target product is obtained through postprocessing processes such as filtering, low-boiling-point substance low-pressure removing and recrystallization. Mother liquid obtained after recrystallization is repeatedly used indiscriminately, and the number of repeating times is larger than five. The synthesizing method has the advantages that the raw material cost is low, the conversion rate is high, postprocessing is simple, chlorinating agents such as thionyl chloride are not required, and three-waste discharging is less; the synthesizing method is suitable for industrial production.
- -
-
Paragraph 0028-0053
(2018/03/25)
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- Discovery of novel β-carboline/acylhydrazone hybrids as potent antitumor agents and overcome drug resistance
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Twenty-four novel β-carboline/acylhydrazone hybrids were synthesized and evaluated for their in vitro antiproliferative activity. Among them, 12r exhibited the most potent activity, with IC50 values of 1–2 μM against panel of cancer cell lines and retained significant activity in multidrug resistant cancer cells. Treated cells were not arrested in any phase of cell cycle but resulted in late cellular apoptosis on both MCF-7 and MCF-7/ADR cancer cells. Importantly, 12r showed certain antitumor effect on inhibiting the tumor growth with low toxic and side effects and without significant body weight loss.
- Li, Yong,Yan, Wei,Yang, Jianhong,Yang, Zhuang,Hu, Mengshi,Bai, Peng,Tang, Minghai,Chen, Lijuan
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p. 516 - 526
(2018/05/23)
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- An auxin-tyrosine derivative based biocompatible supergelator: A template for fabrication of nanoparticles for sustained release of model drugs
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Bioinspired self-assembling peptides serve as powerful building blocks in the manufacturing of nanomaterials with tailored features. Inspired by the supergelating ability of naphthyl-Phe-OH (hydrogelator I), we synthesized naphthyl-Tyr-OH (hydrogelator II) and naphthyl-Trp-OH (hydrogelator III) with the objective of exploring the propensities of the phenolic OH of Tyr and the NH of the indole for controlling the gelation process. However, our experimental investigation reveals that hydrogelator II, containing Tyr as the aromatic core, shows an excellent gelation ability. But the Trp analogue fails to do so under similar conditions. To validate our results we performed MD simulation in an aqueous environment which significantly justifies that hydrogelator II exhibits a better hydrogelation ability than hydrogelators I and III. The characterisation of hydrogelator II was then performed in detail using various analytical and microscopic techniques and its biocompatibility was tested using an MTT assay. To examine the potentiality of hydrogelator II in drug delivery we developed hydrogel nanoparticles (HNPs) using the concept of self-assembly entirely governed by an ecofriendly approach i.e. weak interactions (like H-bonding, π-π and hydrophobic interactions). Our hydrogel nanoparticles display good release kinetics of the model drugs 5-fluorouracil and curcumin from the hydrogel matrix depending on their chemical structure, molecular weight and hydrophobicity. Thus our research shows that the choice of the core residue has a profound impact on the self-assembly process and thus on the gelation properties. Moreover, nanoparticles generated from our novel biocompatible hydrogelator II hold promise for future drug delivery applications.
- Tiwari, Priyanka,Basu, Anindya,Sahu, Sonu,Gound, Sadhna,Christman, Ryann M.,Tiwari, Amit K.,Trivedi, Piyush,DuttKonar, Anita
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p. 4915 - 4922
(2018/03/30)
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- Preparation method of Tadalafil isomer
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The invention discloses a preparation method of a Tadalafil isomer, and belongs to the technical field of drug synthesis. The preparation method comprises the following steps: placing Tadalafil into anon-proton strong polar solvent, and performing partial racemization by using an organic base to obtain an isomer I; performing total synthesis on L-tryptophan serving as a raw material through a four-step reaction to obtain an isomer II; placing the isomer II into the non-proton strong polar solvent, and performing partial racemization by using an organic base to obtain an isomer III; performingstructure confirmation on the three isomers. The preparation method provided by the invention has the advantages of simple procedure, high yield, easiness in post-treatment and easiness in purification.
- -
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Paragraph 0037-0040
(2018/05/16)
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- Design and synthesis of novel monoterpenoid indole alkaloid-like analogues and their antitumour activities: In vitro
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A biomimetic synthetic strategy and combinatorial chemistry were used to synthesize 34 novel monoterpenoid indole alkaloid (MIA) analogues, and their cytotoxic activities against five cancer cell lines (SW-480, A-549, HL-60, SMMC-7721, and MCF-7) were determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Fourteen of these analogues (7, 16-18, and 23-32) showed significantly greater inhibition of tumour cell proliferation than cisplatin. Compounds 17 and 18 showed the highest cytotoxic activity against the HL-60 cell line with IC50 values of 0.90 μM and 0.43 μM, respectively. Compound 18 slightly induced apoptosis and arrested the cell cycle in SW-480, A-549, HL-60, SMMC-7721, and MCF-7 cells. Analysis of the primary structure-activity relationships reveals that the introduction of different substituent groups at the C-3, C-5, and C-6 positions of the indole moiety and the C-10 position of the genipin moiety might have an effect on the antitumour activity of the resulting compounds.
- Fang, Jiaqi,Huang, Tao,Xia, Mengyuan,Deng, Lulu,Hao, Xiaojiang,Wang, Yuehu,Mu, Shuzhen
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supporting information
p. 3026 - 3037
(2018/05/03)
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- A novel high-capacity immunoadsorbent with PAMAM dendritic spacer arms by click chemistry
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Polyamidoamine (PAMAM) dendrimers, bearing multiple peripheral end groups that can be used as clickable modules, make it possible to bind a large number of small-molecule ligands via click chemistry to prepare high-capacity immunoadsorbents. Thus, an immunoadsorbent with PAMAM dendritic spacer arms possessing pseudo-biospecific affinity for IgG from human plasma, Sep-PAMAM-AA, was designed and prepared by click chemistry using sepharose gel as a support and the amino acids His, Phe and Trp as ligands; two sepharose-based control samples, Sep-triazole-His and Sep-PA, with linear spacer arms were prepared using l-histidine and protein A as ligands, respectively. The ligand density and IgG adsorption performance of Sep-PAMAM-AA from human plasma were measured and evaluated. The influences of the structure and generation number of the PAMAM spacer arms on the performances of the products were also investigated. The results indicate that the immunoadsorbent with PAMAM G3 as a spacer arm and His as a ligand, Sep-G3-His, is the best among the prepared immunoadsorbents. Its ligand density reaches 1.58 mmol g?1 sepharose gel, almost 5-fold higher than that of Sep-triazole-His; its IgG adsorption capacity is 28.43 mg g?1, which is higher than those of Sep-triazole-His and Sep-PA. Moreover, Sep-G3-His exhibits a relatively low level of non-specific adsorption, which indicates that the immunoadsorbents with PAMAM as a spacer arm and His as a ligand are expected to have great application prospects in the field of blood purification.
- Hu, Xiaoyan,Li, Guangji,Lin, Yinlei
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p. 15726 - 15732
(2018/10/04)
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- Novel Glycoprotein VI Antagonists as Antithrombotics: Synthesis, Biological Evaluation, and Molecular Modeling Studies on 2,3-Disubstituted Tetrahydropyrido(3,4-b)indoles
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The development of small molecule inhibitors targeting GPVI has promising therapeutic role, as they inhibit arterial thrombosis with limited risk of bleeding. Among the compounds showing in vivo antithrombotic activity, the most active compound 6b (ED50 = 28.36 μmol/kg po in mice) showed improved inhibition for collagen (IC50 = 6.7 μM), CRP-XL (IC50 = 53.5 μM), and convulxin (CVX) (IC50 = 5.7 μM) mediated platelet aggregation as compared to losartan (LOS) (collagen, IC50 = 10.4 μM; CRP-XL, IC50 = 158 μM; CVX, IC50 = 11 μM) than any of its enantiomers S (6c) (collagen, IC50 = 25.3 μM; CRP-XL, IC50 = 181.4 μM; CVX, IC50 = 9 μM) and R (6d) (collagen, IC50 = 126.3 μM; CRP-XL, IC50 > 500 μM; CVX, IC50 = 86.8 μM). Compound 6b also inhibited platelet P-selectin expression and thus may diminish atherosclerosis. The molecular interactions of both enantiomers 6c and 6d at the GPVI receptor have been explained through docking studies.
- Bhunia, Shome S.,Misra, Ankita,Khan, Imran A.,Gaur, Stuti,Jain, Manish,Singh, Surendra,Saxena, Aaruni,Hohlfield, Thomas,Dikshit, Madhu,Saxena, Anil K.
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p. 322 - 337
(2017/04/26)
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- G1/G0 phase retardation of the pentacyclic indole quinolizine, its synthesis, anti-tumor activity and application
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The invention discloses G1/G0-phase blocked pentacyclic indol-quinolizidine which is (6S)-3-acetyl-6-(N-phenylacetyl amino acyl)-oxidative methyl-4,6,7,12-tetrahydro-4-oxoindole-[2,3-1] quinolizidine, and discloses a compound, cell proliferation resistance activity, antineoplastic activity and application thereof.
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Paragraph 0020-0021
(2017/08/31)
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- Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators
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Developing specific chemical functionalities to deploy in biological environments for targeted enzyme inactivation lies at the heart of mechanism-based inhibitor development but also is central to other protein-tagging methods in modern chemical biology including activity-based protein profiling and proteolysis-targeting chimeras. We describe here a previously unknown class of potential PLP enzyme inactivators; namely, a family of quaternary, α-(1′-fluoro)vinyl amino acids, bearing the side chains of the cognate amino acids. These are obtained by the capture of suitably protected amino acid enolates with β,β-difluorovinyl phenyl sulfone, a new (1′-fluoro)vinyl cation equivalent, and an electrophile that previously eluded synthesis, capture and characterization. A significant variety of biologically relevant AA side chains are tolerated including those for alanine, valine, leucine, methionine, lysine, phenylalanine, tyrosine, and tryptophan. Following addition/elimination, the resulting transoid α-(1′-fluoro)-β-(phenylsulfonyl)vinyl AA-esters undergo smooth sulfone-stannane interchange to stereoselectively give the corresponding transoid α-(1′-fluoro)-β-(tributylstannyl)vinyl AA-esters. Protodestannylation and global deprotection then yield these sterically encumbered and densely functionalized quaternary amino acids. The α-(1′-fluoro)vinyl trigger, a potential allene-generating functionality originally proposed by Abeles, is now available in a quaternary AA context for the first time. In an initial test of this new inhibitor class, α-(1′-fluoro)vinyllysine is seen to act as a time-dependent, irreversible inactivator of lysine decarboxylase from Hafnia alvei. The enantiomers of the inhibitor could be resolved, and each is seen to give time-dependent inactivation with this enzyme. Kitz-Wilson analysis reveals similar inactivation parameters for the two antipodes, L-α-(1′-fluoro)vinyllysine (Ki = 630 ± 20 μM; t1/2 = 2.8 min) and D-α-(1′-fluoro)vinyllysine (Ki = 470 ± 30 μM; t1/2 = 3.6 min). The stage is now set for exploration of the efficacy of this trigger in other PLP-enzyme active sites.
- McCune, Christopher D.,Beio, Matthew L.,Sturdivant, Jill M.,De La Salud-Bea, Roberto,Darnell, Brendan M.,Berkowitz, David B.
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supporting information
p. 14077 - 14089
(2017/10/17)
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- Non-peptide tachykinin receptor antagonist preparation method
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The invention discloses a non-peptide tachykinin receptor antagonist preparation method. A synthetic route of a non-peptide tachykinin receptor antagonist is as shown in the specification. The non-peptide tachykinin receptor antagonist preparation method has advantages of simplicity and feasibility in operation, cheap and easy in acquisition of raw materials, high reaction efficiency and high repeatability.
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Paragraph 0021; 0022; 0023; 0024
(2017/08/29)
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- A tadalafil intermediate preparation method
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The invention relates to an improved method of preparing a compound (II). The improved method comprises the following steps: (the formula is shown in the description) 1, mixing D-tryptophan, methanol and toluene, adding thionyl chloride dropwise, and then carrying out reaction at the temperature of 70-85 DEG C to obtain D-tryptophan ester hydrochloride, wherein the structure is shown in a formula (III):(the formula is shown in the specification); and 2, mixing the D-tryptophan ester hydrochloride, a compound (IV) and a nitrile solvent, uniformly stirring, then raising the temperature to 75-85 DEG C, and carrying out reaction, (the formula is shown in the description). The improved preparation method of the compound shown by the D-tryptophan ester hydrochloride (II) has the following beneficial effects: 1, the dosage of the thionyl chloride in the first step is greatly reduced, so that the risk and the corrosion of the reaction are lowered, the post-processing is simple, and the yield is above 90 percent; 2, in the second step, the nitrile solvent is adopted to improve the stereoselectivity, and the enantiomer extra amount (ee %) is above 99 percent.
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Paragraph 0026; 0027
(2017/05/27)
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- Synthesis and evaluation of xanthine oxidase inhibitory and antioxidant activities of 2-arylbenzo[b]furan derivatives based on salvianolic acid C
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Xanthine oxidase (XO) is the key enzyme in humans which is related to a variety of diseases such as gout, hyperuricemia and cardiovascular diseases. In this work, a series of 2-arylbenzo[b]furan derivatives were synthesized based on salvianolic acid C, and they were evaluated for xanthine oxidase inhibitory and antioxidant activities. Compounds 5b, 6a, 6e and 6f showed potent xanthine oxidase inhibitory activities with IC50values ranging from 3.99 to 6.36?μM, which were comparable with that of allopurinol. Lineweaver-Burk plots analysis revealed that the representative derivative 6e could bind to either xanthine oxidase or the xanthine oxidase-xanthine complex, which exhibited a mixed-type competitive mechanism. A DPPH radical scavenging assay showed most of the hydroxyl-functionalized 2-arylbenzo[b]furan derivatives possessed the potent antioxidant activity, which was further validated on LPS-stimulated RAW 264.7 macrophages model. The structure-activity relationships were preliminary analyzed and indicated that the structural skeleton of 2-arylbenzo[b]furan and phenolic hydroxyl groups played an important role in maintaining xanthine oxidase inhibitory effect and antioxidant property for the series of derivatives. Meanwhile, molecular docking studies were performed to further confirm the structure-activity relationships and investigate the proposed binding mechanisms of compounds 5d, 6d and 10d binding to the protein.
- Tang, Hong-Jin,Zhang, Xiao-Wei,Yang, Lin,Li, Wei,Li, Jia-Huang,Wang, Jin-Xin,Chen, Jun
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p. 637 - 648
(2016/09/14)
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- TRIPEPTIDE BORONIC ACID OR BORONIC ESTER, PREPARATIVE METHOD AND USE THEREOF
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The present invention discloses proteasome inhibitors of tripeptide boronic acids or boronic esters represented by Formula (I), preparative method and use thereof. The proteasome inhibitors are therapeutical agents for treating malignant tumor, various nervous system degenerative diseases, muscle cachexia or diabetes, wherein the malignant tumor is leukemia, gastric cancer, hepatocarcinoma or nasopharyngeal carcinoma.
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Paragraph 0035; 0059
(2016/11/07)
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- Preparation of the optically pure N-methyl amino ester method and product
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The invention belongs to the field of organic synthesis of amino acids and discloses a method for preparing optically pure N-methyl amino-acid ester. The method comprises the following steps of carrying out esterification reaction on amino acid as a starting raw material and aldehyde to form an imine intermediate, carrying out reductive amination in the presence of palladium carbon, and carrying out hydrogenation and debenzylation to finally synthesize optically pure N-methyl amino-acid ester. The method has the advantages of simplicity in method, mild reaction conditions and good adaptability and side chains of D-type or L-type amino acid do not need to be protected.
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Paragraph 0045-0047
(2017/04/13)
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- Design, synthesis, and in vitro and biological evaluation of potent amino acid-derived thiol inhibitors of the metallo-β-lactamase IMP-1
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There are currently no clinically available inhibitors of metallo-β-lactamases (MBLs). These enzymes confer resistance to bacteria against a broad range of commonly used β-lactam antibiotics, and are produced by an increasing number of bacterial pathogens. In this study, several thiol derivatives of l-amino acids were designed and synthesized, and their inhibitory effects against the metallo-β-lactamase IMP-1 (subclass B1) were investigated. The most potent compound, derived from l-tyrosine, exhibited competitive inhibition, with a Ki of 86 nM. The ability of this compound to render MBL-expressing bacteria susceptible to imipenem was examined. Reductions in MIC values up to 5.2 - fold were observed.
- Arjomandi, Omid Khalili,Hussein, Waleed M.,Vella, Peter,Yusof, Yusralina,Sidjabat, Hanna E.,Schenk, Gerhard,McGeary, Ross P.
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p. 318 - 327
(2016/04/05)
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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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- Synthesis and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan as gastrosparing NSAIDS
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Synthesis, physicochemical characterization and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan have been attempted to develop novel gastrosparing NSAIDs, devoid of ulcerogenic side effects. The structures of synthesized prodrugs were confirmed by IR, 1H NMR, 13C NMR and mass spectroscopy. The hydrolysis kinetics studies were performed in simulated gastric fluid, simulated intestinal fluid and rat fecal matter. Its anti-inflammatory and ulcer index were analyzed along with estimation of biochemical parameters (GWM and Hexosamine), oxidative parameters (LPO, GSH, CAT, and SOD) and protein estimation. The results indicated that the synthesized prodrugs are chemically stable, biolabile and possesses optimum lipophilicity. They also exhibited retention of anti-inflammatory activity with reduced ulcerogenicity. The study showed that the mutual prodrugs are better in action compared to the parent drug and have fewer gastrointestinal side effects.
- Rasheed, Arun,Lathika,Raju, Y. Prasanna,Mansoor,Azeem,Balan, Nija
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- Synthesis of 10b-fluorinated analogues of protubonine a and its 11a-epimer via fluorocyclisation of tryptophan-containing dipeptides
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The synthesis of 10b-fluorinated analogues of protubonine A and its 11a-epimer was accomplished using fluorocyclisation of tryptophan-containing dipeptides with N-fluoro-2,4,6-trimethylpyridinium triflate to 3a-fluoropyrrolo[2,3-b]indoles as a key step. Acetylation of the indole nitrogen and the following diketopiperazine formation gave the 10b-fluorinated analogues of protubonine A and its 11a-epimer.
- Fujiwara, Tomoya,Yasuda, Hiroko,Nishimura, Yushi,Nambu, Hisanori,Yakura, Takayuki
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p. 5464 - 5473
(2015/02/19)
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- Synergism between genome sequencing, tandem mass spectrometry and bio-inspired synthesis reveals insights into nocardioazine B biogenesis
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Marine actinomycete-derived natural products continue to inspire chemical and biological investigations. Nocardioazines A and B (3 and 4), from Nocardiopsis sp. CMB-M0232, are structurally unique alkaloids featuring a 2,5-diketopiperazine (DKP) core functionalized with indole C3-prenyl as well as indole C3- and N-methyl groups. The logic of their assembly remains cryptic. Bioinformatics analyses of the Nocardiopsis sp. CMB-M0232 draft genome afforded the noz cluster, split across two regions of the genome, and encoding putative open reading frames with roles in nocardioazine biosynthesis, including cyclodipeptide synthase (CDPS), prenyltransferase, methyltransferase, and cytochrome P450 homologs. Heterologous expression of a twelve gene contig from the noz cluster in Streptomyces coelicolor resulted in accumulation of cyclo-l-Trp-l-Trp DKP (5). This experimentally connected the noz cluster to indole alkaloid natural product biosynthesis. Results from bioinformatics analyses of the noz pathway along with challenges in actinomycete genetics prompted us to use asymmetric synthesis and mass spectrometry to determine biosynthetic intermediates in the noz pathway. The structures of hypothesized biosynthetic intermediates 5 and 12-17 were firmly established through chemical synthesis. LC-MS and MS-MS comparison of these synthetic compounds with metabolites present in chemical extracts from Nocardiopsis sp. CMB-M0232 revealed which of these hypothesized intermediates were relevant in the nocardioazine biosynthetic pathway. This established the early and mid-stages of the biosynthetic pathway, demonstrating that Nocardiopsis performs indole C3-methylation prior to indole C3-normal prenylation and indole N1′-methylation in nocardioazine B assembly. These results highlight the utility of merging bioinformatics analyses, asymmetric synthetic approaches, and mass spectrometric metabolite profiling in probing natural product biosynthesis.
- Alqahtani, Norah,Porwal, Suheel K.,James, Elle D.,Bis, Dana M.,Karty, Jonathan A.,Lane, Amy L.,Viswanathan, Rajesh
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supporting information
p. 7177 - 7192
(2015/07/01)
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- Unified mild reaction conditions for C2-selective Pd-catalysed tryptophan arylation, including tryptophan-containing peptides
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Pd-mediated C-H bond functionalisation protocols have been designed and developed on tryptophan derivatives and tryptophan-containing peptides. The examination of different arylation reactions (three sets of different conditions A-C), all of which are notable for their low temperatures (≤40°C), allowed identification of unified and complementary synthetic approaches toward a series of functionalised tryptophan-containing products. Tryptophan-containing peptides demonstrated to be susceptible to aromatic oxidation were successfully and selectively modified through the application of diaryliodonium salts in good yields.
- Reay, Alan J.,Williams, Thomas J.,Fairlamb, Ian J. S.
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p. 8298 - 8309
(2015/08/03)
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- Synthesis and biological evaluation of peptidomimetics containing the tryptamine moiety as a potential antitumor agent
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Three series of novel peptidomimetics bearing the tryptamine moiety were designed, synthesized, and evaluated for their inhibition activities against cell proliferation. According to the preliminary studies on cytotoxic activities, some of the newly prepared compounds (Ia-k, IIa-d, IIIa-g) displayed significant inhibition activities against human hepatoma cancer (HepG2 and Huh-7), and human melanoma (A875) cell lines compared with the control 5-fluorouracil. Especially, compounds Ih and Ij exhibited obvious inhibition activities (Ih IC50 = 4.88 ± 0.78 μg mL-1; Ij IC50 = 6.60 ± 1.20 μg mL-1) against 5-fluorouracil-resistant human hepatocellular carcinoma (BEL-7402/5-FU) cell lines. This journal is
- Wang, Xiaohui,Su, Haihuan,Chen, Changshui,Cao, Xiufang
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p. 15597 - 15602
(2015/03/05)
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- Improved synthesis of tadalafil using dimethyl carbonate and ionic liquids
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An improved synthesis of tadalafil, a drug for the treatment of male erectile dysfunction, involves the use of safer solvents and reagents as well as a reduced number of steps.
- Earle, Martyn J.,Noe, Marco,Perosa, Alvise,Seddon, Kenneth R.
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p. 1204 - 1211
(2014/01/06)
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- ORGANOGOLD COMPLEXES AND METHODS FOR MAKING THE SAME
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The present invention relates to chiral ligands deriving from α- and β-amino acids, and from metal complexes formed from the same. The ligands are useful with catalytic gold complexes, particularly Au(I) complexes.
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Paragraph 0400-0404
(2014/02/16)
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- N-SUBSTITUTED ISOPROPYLDIMETHYL AZULENE SULFONAMIDE DERIVATIVES, AND PREPARATION METHOD AND USE THEREOF
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The present invention provides an N-substituted isopropyldimethyl azulene sulfonamide derivative as represented by formula (I), and preparation method and uses thereof, wherein R1 is an alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, amino, or a substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and amino. The N-substituted isopropyldimethyl azulene sulfonamide derivative can be used in treating gastric ulcer.
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Paragraph 0111
(2014/08/06)
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