Design and synthesis of novel pyrimido[5,4-d]pyrimidine derivatives as GPR119 agonist for treatment of type 2 diabetes.

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：:Oleoyl Formononetin (OF) has good weight loss activity and hypolipidemic activity, could improve insulin sensitivity and suppress adipogenesis. To acquire better biological activities, three series of flavonoid fatty acid esters were designed and synthesized by optimizing the structure of OF. Their bioactivities were ...

journal_title：Bioorganic & medicinal chemistry

authors： Zhao W,Sun J,Xiang H,Zeng YY,Li XB,Xiao H,Chen DY,Ma RL

更新日期：2011-05-15 00:00:00

abstract：:In order to improve the discovery and development of new drugs, a broad effort is being made to assess the 'drug-like' properties of molecules in early stages of the discovery-research process. Although there are numerous approaches to this problem, perhaps the simplest and most widespread one is that developed by Chr...

journal_title：Bioorganic & medicinal chemistry

authors： Petit J,Meurice N,Kaiser C,Maggiora G

更新日期：2012-09-15 00:00:00

abstract：:Leinamycin (1) is a Streptomyces-derived natural product that displays nanomolar IC(50) values against human cancer cell lines. In the work described here, we report the synthesis and characterization of a small leinamycin analogue 19 that closely resembles the 'upper-right quadrant' of the natural product, consisting...

journal_title：Bioorganic & medicinal chemistry

authors： Keerthi K,Rajapakse A,Sun D,Gates KS

更新日期：2013-01-01 00:00:00

abstract：:Two types of nonspacer- and spacer-N-linked tetravalent glycosides bearing N-acetylglucosamine (GlcNAc), N,N'-diacetylchitobiose [(GlcNAc)(2)] and N-acetyllactosamine (LacNAc) were designed and prepared as glycomimetics. The interactions of wheat germ (Triticum vulgaris) agglutinin (WGA) and coral tree (Erythrina cris...

journal_title：Bioorganic & medicinal chemistry

authors： Masaka R,Ogata M,Misawa Y,Yano M,Hashimoto C,Murata T,Kawagishi H,Usui T

更新日期：2010-01-15 00:00:00

abstract：:We have synthesized several conformationally constrained dipeptide analogues as possible substrates for incorporation into proteins. These have included three cyclic dipeptides formed from Boc derivatives of 2,4-diaminobutyric acid, ornithine and lysine, having 5-, 6-, and 7-membered lactam rings, respectively. These ...

journal_title：Bioorganic & medicinal chemistry

authors： Zhang C,Bai X,Dedkova LM,Hecht SM

更新日期：2020-09-23 00:00:00

abstract：:Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)2(sac)2]·H2O (1), trans-[Pt(2-hmpy)2(sac)2]·3H2O (2), trans-[Pd(2-hepy)2(sac)2] (3) and trans-[Pt(2-hepy)2(sac)2] (4), have been synthesized and char...

journal_title：Bioorganic & medicinal chemistry

authors： Ari F,Aztopal N,Icsel C,Yilmaz VT,Guney E,Buyukgungor O,Ulukaya E

更新日期：2013-11-01 00:00:00

abstract：:A series of twenty-two BODIPY compounds were synthesized, containing various meso-phenyl and meso-thienyl groups, and their spectroscopic and structural properties were investigated using both experimental and computational methods. Further functionalization of the BODIPY framework via iodination at the 2,6-pyrrolic p...

journal_title：Bioorganic & medicinal chemistry

authors： Gibbs JH,Robins LT,Zhou Z,Bobadova-Parvanova P,Cottam M,McCandless GT,Fronczek FR,Vicente MG

更新日期：2013-09-15 00:00:00

abstract：:Oligo/polysialic acids consisting of consecutive α(2,8)-linkages on gangliosides and glycoproteins play a role in cell adhesion and differentiation events in a manner that is dependent on the degree of polymerization (DP). Anti-oligo/polysialic acid antibodies often have DP-dependent antigenic specificity, and such un...

journal_title：Bioorganic & medicinal chemistry

authors： Hanashima S,Sato C,Tanaka H,Takahashi T,Kitajima K,Yamaguchi Y

更新日期：2013-10-01 00:00:00

abstract：:The physiology of the oxytocin receptor has increasingly become a focus of scientific investigation due to its connection with social behavior and psychiatric disorders with impairments in social funciton. Experimental utilization of small molecule and peptide antagonists for the oxytocin receptor has played a role in...

journal_title：Bioorganic & medicinal chemistry

authors： Smith AL,Walum H,Connor-Stroud F,Freeman SM,Inoue K,Parr LA,Goodman MM,Young LJ

更新日期：2017-01-01 00:00:00

abstract：:To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (K(i)=5.5nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in rad...

journal_title：Bioorganic & medicinal chemistry

authors： Lee BC,Kim JS,Kim BS,Son JY,Hong SK,Park HS,Moon BS,Jung JH,Jeong JM,Kim SE

更新日期：2011-05-01 00:00:00

abstract：:T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). T22, an 18-residue peptide amide, takes an antiparallel beta-sheet structure that is maintained by two disulfide bridges. Herein we synthesize...

journal_title：Bioorganic & medicinal chemistry

authors： Tamamura H,Waki M,Imai M,Otaka A,Ibuka T,Waki K,Miyamoto K,Matsumoto A,Murakami T,Nakashima H,Yamamoto N,Fujii N

更新日期：1998-04-01 00:00:00

abstract：:Tertiary sulfonamidomethyl esters of benzylpenicillin (4) were synthesised and evaluated as a new class of potential prodrugs for beta-lactam antibiotics. Their hydrolysis in aqueous buffers was studied by HPLC and reveal a U-shaped pH rate profile with a pH-independent process extending from ca. pH 2 to ca. pH 10. Th...

journal_title：Bioorganic & medicinal chemistry

authors： Iley J,Barroso H,Moreira R,Lopes F,Calheiros T

更新日期：2000-07-01 00:00:00

abstract：:We described the synthesis of a new congener series of 1,2,3-triazolyl-4-oxoquinolines and evaluated their ability to inhibit oseltamivir (OST)-resistant influenza strains. Oxoquinoline derivative 1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity...

journal_title：Bioorganic & medicinal chemistry

authors： Boechat Fda C,Sacramento CQ,Cunha AC,Sagrillo FS,Nogueira CM,Fintelman-Rodrigues N,Santos-Filho O,Riscado CS,Forezi Lda S,Faro LV,Brozeguini L,Marques IP,Ferreira VF,Souza TM,de Souza MC

更新日期：2015-12-15 00:00:00

abstract：:Based on the spirotryprostatin-A structure, we designed, synthesized, and evaluated different series of compounds belonging to the diketopiperazine structural class as potential cell cycle modulators and cytotoxic agents. Starting from the spirooxoindolthiazolidine scaffold, amide coupling with Pro derivatives and int...

journal_title：Bioorganic & medicinal chemistry

authors： Bertamino A,Aquino C,Sala M,Simone Nd,Mattia CA,Erra L,Musella S,Iannelli P,Carotenuto A,Grieco P,Novellino E,Campiglia P,Gomez-Monterrey I

更新日期：2010-06-15 00:00:00

abstract：:A series of mechanism-based inhibitors designed to interact with the S' subsites of serine proteases was synthesized and their inhibitory activity toward the closely-related serine proteases human neutrophil elastase (HNE) and proteinase 3 (PR 3) was investigated. The compounds were found to be time-dependent inhibito...

journal_title：Bioorganic & medicinal chemistry

authors： Li Y,Dou D,He G,Lushington GH,Groutas WC

更新日期：2009-05-15 00:00:00

abstract：:The synthesis and biological evaluation of caffonyl pyrrolidine derivatives as MMPs inhibitors are reported in this paper. Inhibiting activities of synthesized compounds on gelatinase (MMP-2 and -9) were tested by using succinylated gelatin as substrate. Structure-activity relationship results from these tested compou...

journal_title：Bioorganic & medicinal chemistry

authors： Li YL,Xu WF

更新日期：2004-10-01 00:00:00

abstract：:Biphenylic compounds related to the natural products magnolol and 4'-O-methylhonokiol were synthesized, evaluated and optimized as positive allosteric modulators (PAMs) of GABA(A) receptors. The most efficacious compounds were the magnolol analog 5-ethyl-5'-hexylbiphenyl-2,2'-diol (45) and the honokiol analogs 4'-meth...

journal_title：Bioorganic & medicinal chemistry

authors： Fuchs A,Baur R,Schoeder C,Sigel E,Müller CE

更新日期：2014-12-15 00:00:00

abstract：:Protein-tyrosine phosphatase (PTP) inhibitors are attractive as potential signal transduction-directed therapeutics which may be useful in the treatment of a variety of diseases. We have previously reported the X-ray structure of 1,1-difluoro-1-(2-naphthalenyl)methyl] phosphonic acid (4) complexed with the human the p...

journal_title：Bioorganic & medicinal chemistry

authors： Yao ZJ,Ye B,Wu XW,Wang S,Wu L,Zhang ZY,Burke TR Jr

更新日期：1998-10-01 00:00:00

abstract：:In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing t...

journal_title：Bioorganic & medicinal chemistry

authors： Ariyasu S,Sawa A,Morita A,Hanaya K,Hoshi M,Takahashi I,Wang B,Aoki S

更新日期：2014-08-01 00:00:00

abstract：:In our previous study on discovering novel types of CCR3 antagonists, we found a fluoronaphthalene derivative (1) that exhibited potent CCR3 inhibitory activity with an IC(50) value of 20 nM. However, compound 1 also inhibited human cytochrome P450 2D6 (CYP2D6) with an IC(50) value of 400 nM. In order to reduce its CY...

journal_title：Bioorganic & medicinal chemistry

authors： Sato I,Morihira K,Inami H,Kubota H,Morokata T,Suzuki K,Iura Y,Nitta A,Imaoka T,Takahashi T,Takeuchi M,Ohta M,Tsukamoto S

更新日期：2008-09-15 00:00:00

abstract：:To investigate the molecular mechanism of vitamin D receptor (VDR) antagonists having no structurally bulky group interfering with helix 12 of the ligand-binding domain of the VDR, we have synthesized four diastereomers at C(20) and C(23) of 19-nor-1alpha-hydroxyvitamin D(3) 25-methylene-26,23-lactone bearing a 2MD-ty...

journal_title：Bioorganic & medicinal chemistry

authors： Yoshimoto N,Inaba Y,Yamada S,Makishima M,Shimizu M,Yamamoto K

更新日期：2008-01-01 00:00:00

abstract：:A series of 8,9-disubstituted adenines (4, 5, 8), 6-substituted aminopurines (10-13) and 9-(p-fluorobenzyl/cyclopentyl)-6-substituted aminopurines (16, 17, 19-30) have been prepared and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and cl...

journal_title：Bioorganic & medicinal chemistry

authors： Tunçbilek M,Ateş-Alagöz Z,Altanlar N,Karayel A,Ozbey S

更新日期：2009-02-15 00:00:00

abstract：:Here we describe the design, synthesis, and pharmacological evaluation of a set of compounds structurally related to the high affinity serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (6, LP-211). Specific structural modifications were performed in order to maintain affini...

journal_title：Bioorganic & medicinal chemistry

authors： Lacivita E,Niso M,Hansen HD,Di Pilato P,Herth MM,Lehel S,Ettrup A,Montenegro L,Perrone R,Berardi F,Colabufo NA,Leopoldo M,Knudsen GM

更新日期：2014-03-01 00:00:00

abstract：:Twelve new flavanones bearing a 2,2-dimethylpyrano ring were isolated from a MeOH extract of the stem bark of Erythrina abyssinica. Their structures were determined on the basis of spectroscopic (UV, CD, 1D and 2D NMR, HRMS) and physico-chemical analyses. Compounds 1, 3, 5, 6, 8, and 9 exhibited inhibitory effects on ...

journal_title：Bioorganic & medicinal chemistry

authors： Cui L,Thuong PT,Lee HS,Ndinteh DT,Mbafor JT,Fomum ZT,Oh WK

更新日期：2008-12-15 00:00:00

abstract：:Gangjee et al. recently reported a novel series of 2-amino-4-methyl-5-phenylethyl substituted-7-benzyl-pyrrolo[2,3-d]pyrimidines, some of which exhibited two digit nanomolar antitumor and antimitotic activity and were not subject to P-glycoprotein (Pgp) or multidrug resistance protein 1 (MRP1) mediated tumor resistanc...

journal_title：Bioorganic & medicinal chemistry

authors： Gangjee A,Namjoshi OA,Keller SN,Smith CD

更新日期：2011-07-15 00:00:00

abstract：:The three trimethylammonium salts 3-5 proved to be 100 times more efficient at alkylating DNA than 2 and exhibited DNA alkylation efficiencies identical to that of (+)-CC-1065 (1). In addition, the agents 3 and 4 exhibited DNA alkylation selectivities identical to that of 2. This may be attributed to spatially well-de...

journal_title：Bioorganic & medicinal chemistry

authors： Boger DL,Yun W,Han N,Johnson DS

更新日期：1995-06-01 00:00:00

abstract：:By the introduction of various amide surrogates, novel pseudopeptides corresponding to a membrane active depsipeptide were synthesized and their native characteristics compared with that of the peptide. The pseudopeptides had more resistance to serum proteases than the peptide and similar antimicrobial activities to t...

journal_title：Bioorganic & medicinal chemistry

authors： Oh JE,Hong SY,Lee KH

更新日期：1999-11-01 00:00:00

abstract：:Luteolin, 5,7-dihydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one, has been proposed and proved to be a novel dopamine transporter (DAT) activator. In order to develop this potential of luteolin, a series of novel luteolin derivatives were designed, synthesized, and evaluated for their DAT agonistic activities, utilizi...

journal_title：Bioorganic & medicinal chemistry

authors： Zhang J,Liu X,Lei X,Wang L,Guo L,Zhao G,Lin G

更新日期：2010-11-15 00:00:00

abstract：:Biological assay guided fractionation of a dichloromethane extract of Synaptolepis kirkii led to the isolation of four new and five known daphnane-type diterpene orthoesters, whose structure was established by spectroscopic data. Full spectroscopic data of the new and known natural products are reported here for the f...

journal_title：Bioorganic & medicinal chemistry

authors： He W,Cik M,Van Puyvelde L,Van Dun J,Appendino G,Lesage A,Van der Lindin I,Leysen JE,Wouters W,Mathenge SG,Mudida FP,De Kimpe N

更新日期：2002-10-01 00:00:00