abstract：:Fibroblast growth factor receptor 3 (FGFR3) is an attractive therapeutic target for the treatment of bladder cancer. We identified 1,3,5-triazine derivative 18b and pyrimidine derivative 40a as novel structures with potent and highly selective FGFR3 inhibitory activity over vascular endothelial growth factor receptor ...

journal_title：Bioorganic & medicinal chemistry

authors： Kuriwaki I,Kameda M,Hisamichi H,Kikuchi S,Iikubo K,Kawamoto Y,Moritomo H,Kondoh Y,Amano Y,Tateishi Y,Echizen Y,Iwai Y,Noda A,Tomiyama H,Suzuki T,Hirano M

更新日期：2020-05-15 00:00:00

abstract：:Hypertension is a diverse illness interlinked with cerebral, cardiovascular (CVS) and renal abnormalities. Presently, the malady is being treated by focusing on Renin- angiotensin system (RAS), voltage-gated calcium channels, peripheral vasodilators, renal and sympathetic nervous systems. Cardiovascular and renal abno...

journal_title：Bioorganic & medicinal chemistry

authors： Ramya K,Suresh R,Kumar HY,Kumar BRP,Murthy NBS

更新日期：2020-05-15 00:00:00

abstract：:The calpains are a conserved family of cysteine proteases that includes several isoforms of which µ-calpain and m-calpain are the most widely distributed in mammalian cells. Calpains have been implicated in normal physiological processes as well as cellular abnormalities such as neurodegenerative disorders, cataract, ...

journal_title：Bioorganic & medicinal chemistry

authors： Donkor IO,Xu J,Liu J,Cameron K

更新日期：2020-05-01 00:00:00

abstract：:A series of new Luotonin A derivatives with substituents at rings A and E was synthesized, together with some E-ring-unsubstituted derivatives. Subsequently, the compound library was examined in silico for their binding into a previously proposed site in the DNA/topoisomerase I binary complex. Whereas no convincing co...

journal_title：Bioorganic & medicinal chemistry

authors： Ibric A,Battisti V,Deckardt S,Haller AV,Lee C,Prötsch C,Langer T,Heffeter P,Schueffl HH,Marian B,Haider N

更新日期：2020-05-01 00:00:00

abstract：:A series of phthalide alkyl tertiary amine derivatives were designed, synthesized and evaluated as potential multi-target agents against Alzheimer's disease (AD). The results indicated that almost all the compounds displayed significant AChE inhibitory and selective activities. Besides, most of the derivatives exhibit...

journal_title：Bioorganic & medicinal chemistry

authors： Luo L,Song Q,Li Y,Cao Z,Qiang X,Tan Z,Deng Y

更新日期：2020-04-15 00:00:00

abstract：:Targeted covalent inhibitors represent an increasingly popular approach to modulate challenging drug targets. Since covalent and non-covalent interactions are both contributing to the affinity of these compounds, evaluation of their reactivity is a key-step to find feasible warheads. There are well-established HPLC- a...

journal_title：Bioorganic & medicinal chemistry

authors： Petri L,Ábrányi-Balogh P,Varga PR,Imre T,Keserű GM

更新日期：2020-04-01 00:00:00

abstract：:A series of novel flurbiprofen-clioquinol hybrids were designed and synthesized as multifunctional agents for Alzheimer's disease therapy, and their potential was evaluated through various biological experiments. In vitro studies showed that most target compounds exhibited significant ability to inhibit self- and Cu2+...

journal_title：Bioorganic & medicinal chemistry

authors： Yang Z,Song Q,Cao Z,Yu G,Liu Z,Tan Z,Deng Y

更新日期：2020-04-01 00:00:00

abstract：:Identification of structural determinants required for potent inhibition of drug-metabolizing cytochrome P450 3A4 (CYP3A4) could help develop safer drugs and more effective pharmacoenhancers. We utilize a rational inhibitor design to decipher structure-activity relationships in analogues of ritonavir, a highly potent ...

journal_title：Bioorganic & medicinal chemistry

authors： Samuels ER,Sevrioukova IF

更新日期：2020-03-15 00:00:00

abstract：:The activity of p90 ribosomal S6 kinase 2 (RSK2) has emerged as an attractive target for cancer therapy due to its role in the regulation of diverse cellular processes, such as cell transformation and proliferation. Several pan-RSK inhibitors have been identified with BI-D1870 and the pseudo-analogs LJH685 and LJI308 ...

journal_title：Bioorganic & medicinal chemistry

authors： Casalvieri KA,Matheson CJ,Backos DS,Reigan P

更新日期：2020-03-01 00:00:00

abstract：:Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis, and a number of Aurora kinase inhibitors have been evaluated in the clinic. Herein we report the synthesis and their antiproliferation of 3,5-disubstituted-2-aminopyrazines as kinases inhibitors. Amongst, 4-((3-am...

journal_title：Bioorganic & medicinal chemistry

authors： Bo YX,Xiang R,Xu Y,Hao SY,Wang XR,Chen SW

更新日期：2020-03-01 00:00:00

abstract：:Radioligand therapy (RLT) using prostate-specific membrane antigen (PSMA) targeting ligands is an attractive option for the treatment of Prostate cancer (PCa) and its metastases. We report herein a series of radioiodinated glutamate-urea-lysine-phenylalanine derivatives as new PSMA ligands in which l-tyrosine and l-gl...

journal_title：Bioorganic & medicinal chemistry

authors： Yao X,Zha Z,Ploessl K,Choi SR,Zhao R,Alexoff D,Zhu L,Kung HF

更新日期：2020-03-01 00:00:00

abstract：:HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is the target of cholesterol-lowering drugs, statins. Previous studies have demonstrated that the enzyme activity is regulated by sterol-induced degradation in addition to transcriptional regulation through sterol-regula...

journal_title：Bioorganic & medicinal chemistry

authors： Sagimori I,Yoshioka H,Hashimoto Y,Ohgane K

更新日期：2020-02-01 00:00:00

abstract：:A nitroreductase (NTR) responsive fluorescent probe, Na-NO2, comprising p-nitrobenzyl as the unique recognition group and 1,8-naphthalimide as fluorophore, was synthesized. Na-NO2 showed remarkable fluorescence "turn-on" signal in the presence of NTR under DMSO/H2O (1:19, v/v) buffered with PBS (pH = 7) solution in th...

journal_title：Bioorganic & medicinal chemistry

authors： Zhang Z,Lv T,Tao B,Wen Z,Xu Y,Li H,Liu F,Sun S

更新日期：2020-02-01 00:00:00

abstract：:Poly(ADP-ribose) glycohydrolase (PARG) plays an essential role in poly(ADP-ribose) (PAR) turnover, and thereby regulating DNA transactions, such as DNA repair, replication, transcription and recombination. Here, we examined the inhibitory activities of 6-hydroxy-3H-xanthene-3-one (HXO) derivatives and analyzed their b...

journal_title：Bioorganic & medicinal chemistry

authors： Shibui Y,Oyama T,Okazawa M,Yoshimori A,Abe H,Uchiumi F,Tanuma SI

更新日期：2020-02-01 00:00:00

abstract：:Thiophene bioisosteres of potent GluN2B receptor negative allosteric modulators were prepared and evaluated pharmacologically. The five-step synthesis of 4,5,7,8-tetrahydro[7]annuleno[b]thiophen-6-one (10) was considerably improved by carboxylation of thiophene-3-carboxylic acid (8) in the first reaction step. Reducti...

journal_title：Bioorganic & medicinal chemistry

authors： Baumeister S,Schepmann D,Wünsch B

更新日期：2020-01-15 00:00:00

abstract：:Aberrant hedgehog (Hh) pathway signaling is implicated in multiple cancer types and targeting the Smoothened (SMO) receptor, a key protein of the Hh pathway, has proven effective in treating metastasized basal cell carcinoma. Our lead optimization effort focused on a series of heteroarylamides. We observed that a meth...

journal_title：Bioorganic & medicinal chemistry

authors： Yang B,Hird AW,Bodnarchuk MS,Zheng X,Dakin L,Su Q,Daly K,Godin R,Hattersley MM,Brassil P,Redmond S,John Russell D,Janetka JW

更新日期：2020-01-15 00:00:00

abstract：:Analogues of the anti-tuberculosis drug bedaquiline, bearing a 3,5-dimethoxy-4-pyridyl C-unit, retain high anti-bacterial potency yet exert less inhibition of the hERG potassium channel, in vitro, than the parent compound. Two of these analogues (TBAJ-587 and TBAJ-876) are now in preclinical development. The present s...

journal_title：Bioorganic & medicinal chemistry

authors： Sutherland HS,Tong AST,Choi PJ,Blaser A,Franzblau SG,Cooper CB,Upton AM,Lotlikar M,Denny WA,Palmer BD

更新日期：2020-01-01 00:00:00

abstract：:Small molecule stimulation of β-cell regeneration has emerged as a promising therapeutic strategy for diabetes. Although chemical inhibition of dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is sufficient to enhance β-cell replication, current lead compounds have inadequate cellular potency for...

journal_title：Bioorganic & medicinal chemistry

authors： Allegretti PA,Horton TM,Abdolazimi Y,Moeller HP,Yeh B,Caffet M,Michel G,Smith M,Annes JP

更新日期：2020-01-01 00:00:00

abstract：:Multifaceted roles of vascular endothelial growth factor (VEGF)-neuropilin-1 (NRP1) interaction have been implicated in cancer, but reports on small-molecule inhibitors of VEGF-NRP1 interaction are scarce. Herein, we describe the identification of 1, a novel nonpeptide small-molecule NRP1 antagonist with moderate acti...

journal_title：Bioorganic & medicinal chemistry

authors： Peng K,Li Y,Bai Y,Jiang T,Sun H,Zhu Q,Xu Y

更新日期：2020-01-01 00:00:00

abstract：:Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identify...

journal_title：Bioorganic & medicinal chemistry

authors： Hinklin RJ,Baer BR,Boyd SA,Chicarelli MD,Condroski KR,DeWolf WE Jr,Fischer J,Frank M,Hingorani GP,Lee PA,Neitzel NA,Pratt SA,Singh A,Sullivan FX,Turner T,Voegtli WC,Wallace EM,Williams L,Aicher TD

更新日期：2020-01-01 00:00:00

abstract：:Twenty-seven natural product-like polyprenylated phenols and quinones were synthesized and their neuroprotective activity was tested using human monoamine oxidase B (MAO-B) and SH-SY5Y cells. Eight compounds inhibited MAO-B (IC50 values < 25 μM) and the inhibition mode and molecular docking of two (8c and 16c) were in...

journal_title：Bioorganic & medicinal chemistry

authors： Kamauchi H,Oda T,Horiuchi K,Takao K,Sugita Y

更新日期：2020-01-01 00:00:00

abstract：:Although cancer cells often harbor supernumerary centrosomes, they form pseudo-bipolar spindles via centrosome clustering, instead of lethal multipolar spindles, and thus avoid cell death. Kinesin-14 HSET/KIFC1 is a crucial protein involved in centrosome clustering. Accordingly, a compound that targets HSET could pote...

journal_title：Bioorganic & medicinal chemistry

authors： Kurisawa N,Yukawa M,Koshino H,Onodera T,Toda T,Kimura KI

更新日期：2020-01-01 00:00:00

abstract：:The AP sites are representative of DNA damage and known as an intermediate in the base excision repair (BER) pathway which is involved in the repair of damaged nucleobases by reactive oxygen species, UVA irradiation, and DNA alkylating agents. Therefore, it is expected that the inhibition or modulation of the AP site ...

journal_title：Bioorganic & medicinal chemistry

authors： Abe YS,Sasaki S

更新日期：2019-12-15 00:00:00

abstract：:The series of des-Cl (unsubstituted) and m-Cl phenyl analogues of PYR with various flexible 6-substituents were synthesized and studied for the binding affinities with highly resistant quadruple mutant (QM) DHFR. The derivatives carrying 4 atoms linker with a terminal carboxyl substituted on the aromatic ring exhibite...

journal_title：Bioorganic & medicinal chemistry

authors： Saepua S,Sadorn K,Vanichtanankul J,Anukunwithaya T,Rattanajak R,Vitsupakorn D,Kamchonwongpaisan S,Yuthavong Y,Thongpanchang C

更新日期：2019-12-15 00:00:00

abstract：:FAAH inhibitors offer safety advantages by augmenting the anandamide levels "on demand" to promote neuroprotective mechanisms without the adverse psychotropic effects usually seen with direct and chronic activation of the CB1 receptor. FAAH is an enzyme implicated in the hydrolysis of the endocannabinoid N-arachidonoy...

journal_title：Bioorganic & medicinal chemistry

authors： Lamani M,Malamas MS,Farah SI,Shukla VG,Almeida MF,Weerts CM,Anderson J,Wood JT,Farizatto KLG,Bahr BA,Makriyannis A

更新日期：2019-12-01 00:00:00

abstract：:In this work, new derivatives of diarylimidazole-1,2,3-triazole 7a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity. All compounds showed potent inhibitory activity in the range of IC50 = 90.4-246.7 µM comparing with acarbose as the standard drug (IC50 = 750.0 µM). Among...

journal_title：Bioorganic & medicinal chemistry

authors： Saeedi M,Mohammadi-Khanaposhtani M,Asgari MS,Eghbalnejad N,Imanparast S,Faramarzi MA,Larijani B,Mahdavi M,Akbarzadeh T

更新日期：2019-12-01 00:00:00

abstract：:We previously identified dibenzooxepine derivative 1 as a potent PPARγ ligand with a unique binding mode owing to its non-thiazolidinedione scaffold. However, while 1 showed remarkably potent MKN-45 gastric cancer cell aggregation activity, an indicator of cancer differentiation-inducing activity induced by PPARγ acti...

journal_title：Bioorganic & medicinal chemistry

authors： Yamamoto K,Tamura T,Nakamura R,Hosoe S,Matsubara M,Nagata K,Kodaira H,Uemori T,Takahashi Y,Suzuki M,Saito JI,Ueno K,Shuto S

更新日期：2019-11-15 00:00:00

abstract：:Phenylpyrazole insecticides are successful for crop protection and public hygiene by blocking gamma-aminobutyric acid (GABA)-gated chloride channels and glutamate-gated chloride (GluCl) channels. A series of novel phenylpyrazoles containing arylimine or 1-methoxyaryl groups were designed and synthesized. The addition ...

journal_title：Bioorganic & medicinal chemistry

authors： Zhao Q,Sun R,Liu Y,Chen P,Li Y,Yang S,Wang Q

更新日期：2019-11-01 00:00:00

abstract：:Since NSAIDs are commonly used anti-inflammatory agents that produce adverse effects, there have been ongoing efforts to develop more effective and less toxic compounds. Based on the structure of the anti-inflammatory pyrrolizines licofelone and ketorolac, a series of 1-arylpyrrolizin-3-ones was synthesized. Also prep...

journal_title：Bioorganic & medicinal chemistry

authors： Madrigal DA,Escalante CH,Gutiérrez-Rebolledo GA,Cristobal-Luna JM,Gómez-García O,Hernández-Benitez RI,Esquivel-Campos AL,Pérez-Gutiérrez S,Chamorro-Cevallos GA,Delgado F,Tamariz J

更新日期：2019-10-15 00:00:00

abstract：:Combretastatin A-4 (CA-4) is a highly cytotoxic natural product and several derivatives have been prepared which underwent clinical trial. These investigations revealed that the cis-stilbene moiety of the natural product is prone to undergo cis/trans isomerization under physiological conditions, reducing the overall a...

journal_title：Bioorganic & medicinal chemistry

authors： Nowikow C,Fuerst R,Kauderer M,Dank C,Schmid W,Hajduch M,Rehulka J,Gurska S,Mokshyna O,Polishchuk P,Zupkó I,Dzubak P,Rinner U

更新日期：2019-10-01 00:00:00

abstract：:When a neutral solution of thymidine and ascorbic acid was irradiated with UV light of wavelength longer than 300 nm in the presence of salicylic acid as a photosensitizer, six product peaks appeared in an HPLC chromatogram in addition to small amounts of thymidine dimers. The six products were identified as three pai...

journal_title：Bioorganic & medicinal chemistry

authors： Suzuki T,Kishida Y

更新日期：2019-10-01 00:00:00

abstract：:A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data an...

journal_title：Bioorganic & medicinal chemistry

authors： Othman DIA,Selim KB,El-Sayed MA,Tantawy AS,Amen Y,Shimizu K,Okauchi T,Kitamura M

更新日期：2019-10-01 00:00:00

abstract：:Platinum compounds are the first-line therapy for many types of cancer. However, drug resistance has frequently been reported for and is a major limitation of platinum-based chemotherapy in the clinic. In the current study, we examined the anti-tumor activity of phomoxanthone A (PXA), a tetrahydroxanthone dimer isolat...

journal_title：Bioorganic & medicinal chemistry

authors： Wang C,Engelke L,Bickel D,Hamacher A,Frank M,Proksch P,Gohlke H,Kassack MU

更新日期：2019-10-01 00:00:00

abstract：:Focused libraries of multi-substituted epidithiodiketopiperazines (ETP) were prepared and evaluated for efficacy of inhibiting the nucleocapsid protein function of the Feline Immunodeficiency Virus (FIV) as a model for HIV. This activity was compared and contrasted to observed toxicity utilising an in-vitro cell cultu...

journal_title：Bioorganic & medicinal chemistry

authors： Asquith CRM,Sil BC,Laitinen T,Tizzard GJ,Coles SJ,Poso A,Hofmann-Lehmann R,Hilton ST

更新日期：2019-09-15 00:00:00

abstract：:Searching for new substances with antileishmanial activity, we synthesized and evaluated a series of α,α-difluorohydrazide and α,α-difluoramides against Leishmania amazonensis arginase (LaArg). Four α,α-difluorohydrazide derivatives showed activity against LaArg with Ki in the range of 1.3-26 μM. The study of the kine...

journal_title：Bioorganic & medicinal chemistry

authors： Crizanto de Lima E,Castelo-Branco FS,Maquiaveli CC,Farias AB,Rennó MN,Boechat N,Silva ER

更新日期：2019-09-01 00:00:00

abstract：:Antagonists of type 1 cannabinoid receptors (CB1) may be useful in treating diabetes, hepatic disorders, and fibrosis. Otenabant (1) is a potent and selective CB1 inverse agonist that was under investigation as an anti-obesity agent, but its development was halted once adverse effects associated with another marketed ...

journal_title：Bioorganic & medicinal chemistry

authors： Amato G,Wiethe R,Manke A,Vasukuttan V,Snyder R,Runyon S,Maitra R

更新日期：2019-08-15 00:00:00

abstract：:Diflumetorim is a member of pyrimidinamine fungicides that possess excellent antifungal activities. Nevertheless, as reported that the activity of diflumetorim to corn rust (Puccinia sorghi) was not ideal (EC50 = 53.26 mg/L). Herein, a series of novel pyrimidinamine derivatives containing phenyl-thiazole/oxazole moiet...

journal_title：Bioorganic & medicinal chemistry

authors： Yan Z,Liu A,Ou Y,Li J,Yi H,Zhang N,Liu M,Huang L,Ren J,Liu W,Hu A

更新日期：2019-08-01 00:00:00

abstract：:Cytosporolide (Cytos) A-C, isolated from the fungus Cytospora sp., have anti-microbial activity, but their molecular targets in mammalian cells are unknown. We have previously reported the total synthesis of Cytos A by biomimetic hetero-Diels-Alder reaction. In this study, to examine the novel bioactivity of Cytos, we...

journal_title：Bioorganic & medicinal chemistry

authors： Otake K,Yamada K,Miura K,Sasazawa Y,Miyazaki S,Niwa Y,Ogura A,Takao KI,Simizu S

更新日期：2019-08-01 00:00:00

abstract：:In the course of our studies of hydrophobic oxytocin (OT) analogues, we newly synthesized lipidated OT (LOT-4a-c and LOT-5a-c), in which a long alkyl chain (C14-C16) is conjugated via a carbonate or carbamate linkage at the Tyr-2 phenolic hydroxy group and a palmitoyl group at the terminal amino group of Cys-1. These ...

journal_title：Bioorganic & medicinal chemistry

authors： Cherepanov SM,Miura R,Shabalova AA,Ichinose W,Yokoyama S,Fukuda H,Watanabe M,Higashida H,Shuto S

更新日期：2019-08-01 00:00:00

abstract：:In recent years, special attention has been paid to the A3 adenosine receptor (A3AR) as a possible pharmacological target to treat intestinal inflammation. In this work, it was set up a novel method to quantify the concentration of a promising anti-inflammatory agent inside and outside of intestinal barrier using the ...

journal_title：Bioorganic & medicinal chemistry

authors： Buccioni M,Dal Ben D,Lambertucci C,Martí Navia A,Ricciutelli M,Spinaci A,Volpini R,Marucci G

更新日期：2019-08-01 00:00:00