Design, synthesis and biological estimation of 1-(benzoxazole-2-y1)piperazine and 4-(benzoxazole-2-yl)piperidine derivatives as potential α1-AR antagonists

Two series of 1-(benzoxazole-2-yl)piperazine(8a-i)and 4-(benzoxazole-2-yl)piperidine compounds(10a-i)were designed,synthesized and evaluated for their α1-AR antagonistic activities.Biological assay in vitro indicated that 10h showed slightly stronger α1-AR antagonistic activity to that of our lead compound 1.     

Design and synthesis of 2-alkylbenzimidazole derivatives as novel non-peptide angiotensin Ⅱ AT1 receptor antagonists

A series of 2-alkylbenzimidazole derivatives 9a-n have been designed and synthesized as a novel class of non-peptide angiotensin Ⅱ AT1 receptor antagonists. The synthesized compounds were evaluated for their antagonism of angiotensin Ⅱ, induced contraction in the rabbit thoracic aortic ring and the results showed that compounds 9a, 9g and 9j exhibited potent antagonistic activity of AT1 receptor.     

Pharmacophore-guided design, synthesis and evaluation of quinazoline-arylpiperazines as new α1-adrenoceptor antagonists

A series of arylpiperazinesquinazoline-2,4-diamine compounds were designed and synthesized based on pharmacophore for uro-selectiveα_1-adrenoceptor antagonists and 3D chemical database searching.The in vitro functional analysis showed that compounds 9 and 14 showed better and similarα_1-AR antagonistic activity compared with prazosin.     

Design,synthesis and biological evaluation of novel quinazoline derivatives as potential NF-κb inhibitors

A series of novel 4-aminoquinazoline derivatives were designed, synthesized and biological properties on nuclear factor-kappaB (NF-κb) pathway inhibitory and potential in vitro anti-proliferation against breast cancer lines were also evaluated. Among them, LU1501 exhibited potent inhibition with IC₅₀ values in SK-BR-3 (10.16 ± 0.86 µM) and HCC1806 (10.66 ± 1.01 µM) cell lines. In vivo studies in breast cancer tumor model proved the correlation between anticancer activity of LU1501 and proliferation inhibition through the NF-κb signal pathway. The molecular docking studies also portrayed the potential binding mechanism between LU1501 and the key proteins of p65 and IkBα in NF-κb pathway. Accordingly, compound LU1501 could serve as a potent agent against breast cancer for further investigation.     

New 3-（4-arylpiperazin-1-yl）-1-（benzo[b]thiophen-3-yl）-2-methylpropanol derivatives：Synthesis and evaluation for dual 5-HT1A/SSRI activities

A series of 3-（4-arylpiperazin-1-yl）-1-（benzo[b]thiophen-3-yl）-2-methylpropanol derivatives were designed and synthesized based on 5-HT1A/SSRI drugs design strategies.The synthesized compounds were evaluated for their dual 5-HT1A/5-HTT activities.     

Synthesis, Crystal Structure and Fluorescent Properties of 1-（4-（Dimethylamino）benzylidene）- 4-（naphthalen- 1-yl） Thiosemicarbazide

1 INTRODUCTION Recently, for the fluorescent properties, Schiff base has been more and more important and widely studied in density optical memories, nonlinear op- tics (NLO), organic light-emitting diodes (OLED), polymer LED and electrogenerated chemilumines- cence (ECL)[1~5]. Thiosemicarbazones are a kind of Schiff bases with thiourea and good ligands easily chelating with transition metal ions. Although they have been studied extensively for a long time due to their chemical and b…     

Design,synthesis and biological evaluation of biphenylurea derivatives as VEGFR-2 kinase inhibitors(Ⅱ)

Inhibition of VEGFR-2 signaling pathway is one of the most promising approaches for the treatment of cancer. In this paper, we reported the design, synthesis, and biological evaluation of a series of biphenylurea derivatives as VEGFR-2 inhibitors. Among these compounds, 39 exhibited potent inhibitory activity against VEGFR-2 both in vitro and in vivo. The antiangiogenesis activity of 39 was further confirmed by both tube formation assay and chick chorioallantoic membrane assay.     

Synthesis, Structure and Biological Activities of 2-（1H- 1,2,3-Benzotriazol-1 -yl ）-1-（ 4- methylphenyl ）-2-（1H-1,2,4-triazol-l-yl）-1-ethanone

The title compound was synthesized and characterized by IR, ^1H NMR, elemental analysis and single crystal X-ray diffraction analysis. Its biological activities were also tested. The results show that the title compound reveals inhibiting activities towards wheat gibberellin, apple ringspot, tomato early blight, peanut cercospora arachidicola and stem wilt of asparagus.     

L-Proline catalyzed one-pot multi-component synthesis of 2-（1,3-diphenyl-1H-pyrazol-4-yl）quinazolin-4（3H）-one derivatives and their biological studies

A new series of quinazolin-4（3H）-one derivatives containing a（1 3-diphenyl-1H-pyrazol-4-yl） core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized using an L-proline catalyzed one-pot multi-component reaction approach.All the synthesized compounds were characterized and screened for their antimicrobial,antifungal and anti-tubercular activities.     

Design,synthesis and biological evaluation of novel 2-phenyl-4,5,6,7-tetrahydro-1H-​indole derivatives as potential anticancer agents and tubulin polymerization inhibitors

A new series of 2-phenyl-4,5,6,7-tetrahydro-1H-?indole derivatives as tubulin polymerization inhibitors were synthesized and evaluated for the anti-proliferative activities. All newly prepared compounds were tested for their antiproliferative activity in vitro on the human breast cancer cell line (MCF-7) and human lung adenocarcinoma cell line (A549). Among them, compound 7b with a 4-methoxyl substituent at the phenylhydrazone moiety exhibited the most potent anticancer activity against MCF-7 and A549 with IC₅₀ values of 1.77 ± 0.37 and 3.75 ± 0.11 μM, respectively. Interestingly, 7b displayed significant selectivity in inhibiting cancer cells over LO2 (normal human liver cells). Further mechanism studies revealed that 7b significantly arrested cell cycle at G2/M phase and induced apoptosis in a dose-dependent manner. Additionally, 7b effectively inhibited tubulin polymerization with an inhibitory manner similar to that of colchicine. Furthermore, molecular docking study suggested that 7b had high binding affinities for the colchicine binding pocket of tubulin. Hence, this study demonstrates for the first time that tetrahydroindole can be used as a functional group for the design and development of new tubulin polymerization inhibitors.     

Design and Synthesis of Novel Aryloxyalkyl-arylpiperazine Derivatives as α_(1A)-Adrenoceptor Antagonists

Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate andclinically occurs predominantly in men aged over 60 years1. α1-Adrenoceptor (α1-AR)antagonists such as terazosin and doxazosin relax the smooth muscle in the prostate andlower urinary tract and are currently being used as treatment for BPH2,3. These clinicalagents, while effective, have been associated with side effects such as orthostatichypotension, dizziness, asthenia, and nasal congestion4. …     

Synthesis, Structure and Biological Activities of 2- （4-Met hoxybenzoyl ）-N-phenyl- 2- （ 1,2,4-triazol- 1-yl ） thioacetamide

The title compound, 2-(methoxybenzoyl)-N-phenyl-2-(1,2,4-triazol-l-yl) thioacetamide was synthesized by several reactions from 4-methoxyacetophenone, triazole and phenyl isothiocyanate. The structure was identified by elemental analysis, ^1H NMR, MS and IR. The single crystal structure of 2-(methoxybenzoyl)-N-phenyl-2-(1,2,4-triazol-l-yl)thioacetamide was determined withX-ray diffraction. The preliminary bioassays show that the title compound exhibits weak antifungal activities and plant-growth regulatory activity.     

Design,synthesis and antitumor activity of 3-substituted quinolone derivatives （Ⅰ）

A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of synthesized compounds showed moderate inhibitory activity against cancer cells. The inhibitory activities of 6k, against KB and A2780 tumor ceils are comparable to that of topotecan, one of topoisomerase I inhibitors.     

Design,synthesis and biological evaluation of 1,4-dihydrothieno[3′,2′:5,6]thiopyrano[4,3-c]pyrazole-3-carboxylic amide derivatives as potential estrogen receptor antagonists

The estrogen receptor is a target for therapeutic agents for hormone replacement in menopausal women,osteoporosis, reproductive cancers such as breast cancer,uterine cancer and prostate cancer.1,4-Dihydrothieno[3’,2’:5,6]thiopyrano[4,3- c]pyrazole-3-carboxylic amide derivatives were designed,synthesized and biological evaluated as potential estrogen receptor antagonists.     

In vitro evaluation of novel mefenamic acid derivatives as potential α-glucosidase and urease inhibitors: Design,synthesis, in silico and cytotoxic studies

This study aim to synthesize new 1,3,4-oxadiazole derivatives incorporating mefenamic acid as promising α-glucosidase and urease inhibitors, potentially leading to the treatment of postprandial hyperglycemia as well as H. pylori related disorders. In this regards, we have designed a series of Mefenamic acid derivatives. The synthetic compounds were structurally elucidated through ¹H NMR, ¹³C NMR and HR-EIMS analysis. The biological evaluation of these derivatives against α-glucosidase and urease enzyme depicted some novel derivatives with potent inhibition against the said enzymes. All the derivatives exhibited potent inhibition against α-glucosidase enzymes with IC₅₀ ranging from 25.81 ± 1.63–113.61 ± 1.31 µM against standard drug acarbose (IC₅₀ = 375.82 ± 1.76 µM) while with respect to urease these derivatives possessed inhibitory potential varied between IC₅₀ = 8.04 ± 1.01–58.18 ± 1.03 µM against the standard thiourea (IC₅₀ = 21.0 ± 1.76 µM). The cell viability results revealed that all of the derivatives were found least cytotoxic. Furthermore, molecular docking studies of the most potent derivatives identify number of key features involved in binding interactions between potential inhibitors and the enzyme's active site.     

Asymmetric Synthesis of （-）-（4R, 5R）-4-[5-（Benzo[1, 3]dioxol-5-yl）-4- hydroxyl- 1-（pyridin-2-yl）-4, 5-dihydro- 1H-pyrazol-3-yl]benzamide

For discovering novel small molecule inhibitors of transforming growth factor-β1(TGF-β1)type-I receptor(ALK5),we designed1,3,5-triaryl-4-hydroxyl-4,5-dihydro-1H-pyrazole(1)as target compound,mimic the structure of SB-431542which is a2-pyridyl substituted triarylimiazole inhibitor of ALK51.Racemic compound1showed moderate ALK5inhibitory activity in luciferase reporter assays[inhibition(%control):0.1umol/L8.79%;1umol/L19.05%].To investigate the influence of the absolute configuration of…     

Synthesis of C-Nucleoside Analogues： 2-[2-（Hydroxymethyl）-1, 3-dioxolan-5-yl]1, 3-thiazole-4-carboxamide and 2-[2-（Mercaptometh-yl）-1, 3-dioxolan-5-yl] 1, 3-thiazole-4-carboxamide

Novel C-nucleosides of tiazofurin analogue (2-[2-(hydroxymethyl)-1,3-dioxolan-5-yl] 1,3-thiazole-4-carboxamide) and its thiol-substituted derivative (2-[2-(mercaptomethyl)-1,3-dioxolan-5-yl] 1, 3-thiazole-4-carboxamide) were synthesized from methyl acrylate through a multistep procedure. Their structures were confirmed by IR, ^1HNMR, ^13CNMR and elemental analysis.