Discovery of phenyl acetamides as potent and selective GPR119 agonists.

abstract：:A series of pyrimidine derivatives as acid pump antagonists (APAs) was synthesized and the inhibitory activities against H(+)/K(+) ATPase isolated from hog gastric mucosa were determined. After elaborating on substituents at C2 and C4 position of the pyrimidine scaffold, we have observed that the compound 7h is a pote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoon YA,Park CS,Cha MH,Choi H,Sim JY,Kim JG

更新日期：2010-10-01 00:00:00

abstract：:To design artificial restriction enzymes, synthetic catalytic centers that effectively hydrolyze linear double-stranded polydeoxyribonucleotides are needed. The Co(III) complex of cyclen (CoCyc) attached to polystyrene derivatives hydrolyzes linearized pUC18 DNA with half-lives as short as 30 min at 25 degrees C. The ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeung CS,Song JB,Kim YH,Suh J

更新日期：2001-12-03 00:00:00

abstract：:A homology model of the nicotinic acid receptor GPR109A was constructed based on the X-ray crystal structure of bovine rhodopsin. An HTS hit was docked into the homology model. Characterization of the binding pocket by a grid-based surface calculation of the docking model suggested that a larger hydrophobic body plus ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deng Q,Frie JL,Marley DM,Beresis RT,Ren N,Cai TQ,Taggart AK,Cheng K,Carballo-Jane E,Wang J,Tong X,Waters MG,Tata JR,Colletti SL

更新日期：2008-09-15 00:00:00

abstract：:Several chemical modifications in the N(1)-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh SK,Reddy PG,Rao KS,Lohray BB,Misra P,Rajjak SA,Rao YK,Venkateswarlu A

更新日期：2004-01-19 00:00:00

abstract：:A new hepatitis C virus (HCV) protease inhibitor designated as Sch 351633 (1) was isolated from the fungus, Penicillium griseofulvum. Structure elucidation of 1 was accomplished by analysis of spectroscopic data, which determined compound 1 to be a bicyclic hemiketal lactone. Compound 1 exhibited inhibitory activity i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu M,Mierzwa R,He L,King A,Patel M,Pichardo J,Hart A,Butkiewicz N,Puar MS

更新日期：1999-07-19 00:00:00

abstract：:The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6'-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dini C,Didier-Laurent S,Drochon N,Feteanu S,Guillot JC,Monti F,Uridat E,Zhang J,Aszodi J

更新日期：2002-04-22 00:00:00

abstract：:Protein conjugation with ubiquitin and ubiquitin-like small molecules, such as UFM1, is important for promoting cancer cell survival and proliferation. Herein, the development of the first selective micromolar inhibitor of the UBA5 E1 enzyme that initiates UFM1 protein conjugation is described. This organometallic inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： da Silva SR,Paiva SL,Bancerz M,Geletu M,Lewis AM,Chen J,Cai Y,Lukkarila JL,Li H,Gunning PT

更新日期：2016-09-15 00:00:00

abstract：:The design and synthesis of new 1alpha,25-dihydroxy-19-norvitamin D(3) analogues 3a-c, which have an amide bond in the molecule instead of the diene, are described. The A-ring moiety was constructed by a (3S,5S)-3,5-dihydroxypiperidine derivative (9, 11, or 13) prepared from D-mannose, and a CD-ring carboxylic acid 16...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suhara Y,Kittaka A,Ono K,Kurihara M,Fujishima T,Yoshida A,Takayama H

更新日期：2002-12-16 00:00:00

abstract：:To improve the drug-ability of celastrol, a series of PEGylation celastrol (PEGC) were designed and synthesized by conjugation with different kinds of polyethylene glycols (PEGs) with celastrol. Most of PEGCs could easily dissolve in water. In particular, one of them (DC1000) could be dispersed in water to form nanopa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shan WG,Wang HG,Wu R,Zhan ZJ,Ma LF

更新日期：2019-03-01 00:00:00

abstract：:We herein report the discovery of a new γ-secretase modulator class with an aminothiazole core starting from a HTS hit (3). Synthesis and SAR of this series are discussed. These novel compounds demonstrate moderate to good in vitro potency in inhibiting amyloid beta (Aβ) peptide production. Overall γ-secretase is not ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lübbers T,Flohr A,Jolidon S,David-Pierson P,Jacobsen H,Ozmen L,Baumann K

更新日期：2011-11-01 00:00:00

abstract：:Horner-Emmons reaction of 4"-dehydro-5-O-TBDMS-avermectin B(1a) with a variety of phosphorus ylides using LHMDS gave novel 4"-alkylidene avermectin derivatives in high yields. Further modifications led to derivatives bearing diverse functional groups. The new avermectin derivatives showed potent growth inhibitory acti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nagai K,Sunazuka T,Shiomi K,Harder A,Turberg A,Omura S

更新日期：2003-11-17 00:00:00

abstract：:We have synthesized and tested novel quinuclidinone analogs to assay the effects on H1299 lung cancer cell lines alone or with gamma-radiation. We have found two series of quinuclidinone analogs that act as anti-cancer agents. Of these, four interesting analogs significantly decreased cell viability in H1299 lung canc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Malki A,Pulipaka AB,Evans SC,Bergmeier SC

更新日期：2006-03-01 00:00:00

abstract：:We report herein the design and synthesis of a series of novel ciprofloxacin (CPFX) derivatives with remarkable improvement in lipophilicity by introducing a substituted benzyl moiety to the N atom on the C-7 piperazine ring of CPFX. Antimycobacterial and antibacterial activity of the newly synthesized compounds was e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang S,Jia XD,Liu ML,Lu Y,Guo HY

更新日期：2012-09-15 00:00:00

abstract：:We demonstrate the synthesis and selective binding of two novel furan based tricyclic homo-oligopeptides to G-quadruplex and using Real Time PCR show its repressive effect on c-MYC transcription. CD spectroscopy and FRET melting studies show that these ligands can induce G-quadruplex structures in the G rich 22 mer c-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agarwal T,Roy S,Chakraborty TK,Maiti S

更新日期：2010-08-01 00:00:00

abstract：:Fast atom bombardment mass spectrometry that can directly analyze lysophospholipids was used to quantitatively determine the kinetics of phospholipase A2. This method is 1250 times more sensitive than the colorimetric assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Isomura S,Ito K,Haruna M

更新日期：1999-02-08 00:00:00

abstract：:Neuraminidase has been considered as an important target for designing agents against influenza viruses. In a discovery of anti-influenza agents with epigoitrin as the initial lead compound, a series of 1-amino-2-alkanols were synthesized and biologically evaluated. The in vitro evaluation indicated that (E)-1-amino-4...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu C,Yin Y,Meng F,Dun Y,Pei K,Wang C,Xu X,Wu F

更新日期：2018-06-15 00:00:00

abstract：:The NMR structures of gentamicin and paromomycin in complex with the A-site of Escherichia coli 16S ribosomal RNA were modified with molecular modeling to 12 analogues. The intermolecular interactions between these molecules and RNA were examined using the HINT (Hydropathic INTeractions) computational model to obtain ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cashman DJ,Rife JP,Kellogg GE

更新日期：2001-01-22 00:00:00

abstract：:A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dai L,Zang C,Tian S,Liu W,Tan S,Cai Z,Ni T,An M,Li R,Gao Y,Zhang D,Jiang Y

更新日期：2015-01-01 00:00:00

abstract：:We report a rapid method for profiling of kinases using a strategy that couples the merits of combinatorics (in rapid diversity generation) with the throughput attainable using microarrays (in parallel screening). Alanine-scanning, deletion and positional-scanning peptide libraries of a kinase substrate were synthesiz...

journal_title：Bioorganic & medicinal chemistry letters

authors： Uttamchandani M,Chan EW,Chen GY,Yao SQ

更新日期：2003-09-15 00:00:00

abstract：:An indole compound with a strong purple-red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE-650S Toyopearl TSK-gel and silica-gel columns. The purple-red compound purified was identified as indoxyl red, on the basis of FAB Mass, (13)C NMR, (1)H NMR, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song J,Kitamatsu M,Imamura K,Ohmori H,Watanabe K,Nakanishi K

更新日期：2013-02-01 00:00:00

abstract：:After the widespread use of the acyclic purine nucleoside analogues for therapy of herpes simplex virus (HSV) infection since the 1980s, new antiviral strategies are urgently needed to counter the emergence of drug-resistant clinical isolates. In this report, we define the anti-HSV efficacies of three optimized 2-amin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiang YF,Qian CW,Xing GW,Hao J,Xia M,Wang YF

更新日期：2012-07-15 00:00:00

abstract：:In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Som...

journal_title：Bioorganic & medicinal chemistry letters

authors： Luo G,Chen L,Civiello R,Pin SS,Xu C,Kostich W,Kelley M,Conway CM,Macor JE,Dubowchik GM

更新日期：2012-04-15 00:00:00

abstract：:The addition of exogenous ent-cholesterol suppressed the antifungal activity of the amphotericin B when added to cultures of Candida albicans, but to a lesser extent than natural cholesterol. There were no detectable differences between added 2a or 2b on the antifungal activities of jaspamide or bengazole A, two unrel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Richter RK,Mickus DE,Rychnovsky SD,Molinski TF

更新日期：2004-01-05 00:00:00

abstract：:With an insight that ligands possessing a N2S2 tetradentate array of donor atoms serve as ideal bifunctional chelating agents (BFCA) in the radiolabeling of target-specific agents, 5-hydroxy-3,7-diazanonan-1,9-dithiol (DAHPES) with a derivatizable substituent in the form of a hydroxyl group in the backbone was synthes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das T,Banerjee S,Samuel G,Bapat K,Subramanian S,Pillai MR,Venkatesh M

更新日期：2006-11-15 00:00:00

abstract：:A series of pentapeptides, based on hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)), was prepared in which either DPhe(7) or Trp(9) residue was systematically substituted. A number of interesting DPhe surrogates (D-Thi, D-3-CF(3)Phe, D-2-Nal and D-3,4-diClPhe) as well as Trp surrogates (2-Na...

journal_title：Bioorganic & medicinal chemistry letters

authors： Danho W,Swistok J,Cheung AW,Kurylko G,Franco L,Chu XJ,Chen L,Yagaloff K

更新日期：2003-02-24 00:00:00

abstract：:Sodium channel blocking, anticonvulsant activity, and sigma (sigma) binding of selected leads in a series of alpha-amino amide anticonvulsants were examined. While anticonvulsant compounds were always endowed with low micromolar sodium (Na+) channel site-2 binding, compounds with low site-2 Na+ channel affinity failed...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pevarello P,Bonsignori A,Caccia C,Amici R,McArthur RA,Fariello RG,Salvati P,Varasi M

更新日期：1999-09-06 00:00:00

abstract：:Eight monosaccharide analogs of the potent antitumor OSW saponins (2-9) were synthesized. One analog, 2-O-acetyl-alpha-l-arabinopyranoside 3, showed antiproliferative activity against the Jurkat cells (IC(50)=0.078microM) comparable to that of the disaccharide derivative (1). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tang P,Mamdani F,Hu X,Liu JO,Yu B

更新日期：2007-02-15 00:00:00

abstract：:Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Robinson RP,Bartlett JA,Bertinato P,Bessire AJ,Cosgrove J,Foley PM,Manion TB,Minich ML,Ramos B,Reese MR,Schmahai TJ,Swick AG,Tess DA,Vaz A,Wolford A

更新日期：2011-07-15 00:00:00

abstract：:Screening of a metalloprotease library led to the identification of a thiol-based dual ACE/NEP inhibitor as a potent ACE2 inhibitor. Modifications of the P(1) benzyl moiety led to improvements in ACE2 potency as well as to increased selectivity versus ACE and NEP. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deaton DN,Gao EN,Graham KP,Gross JW,Miller AB,Strelow JM

更新日期：2008-01-15 00:00:00

abstract：:Based on the theoretical understanding of the in vivo lysosomotropism, by adjusting the pk(a) of basic nitrogen containing cathepsin S inhibitors, a set of compounds with pk(a) 6-8 were identified to have excellent cell based Lip10 activity, yet avoiding undesired sequestration in spleen. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arbuckle W,Baugh M,Belshaw S,Bennett DJ,Bruin J,Cai J,Cameron KS,Claxton C,Dempster M,Everett K,Fradera X,Hamilton W,Jones PS,Kinghorn E,Long C,Martin I,Robinson J,Westwood P

更新日期：2011-02-01 00:00:00