Novel non-benzimidazole chk2 kinase inhibitors.

abstract：:A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-N...

journal_title：Bioorganic & medicinal chemistry letters

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

更新日期：2003-04-07 00:00:00

abstract：:Silybin is the major flavonolignan of silymarin and it displays a plethora of biological effects, generally ascribed to its antioxidant properties. Herein we shall describe an efficient synthetic strategy to obtain a variety of new and more water-soluble silybin and 2,3-dehydrosilybin (DHS) derivatives in which the 23...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zarrelli A,Sgambato A,Petito V,De Napoli L,Previtera L,Di Fabio G

更新日期：2011-08-01 00:00:00

abstract：:We expand the structural requirements and structure-activity relationship of a novel class of non-peptidic aryl-based thrombin inhibitors through exploration of the S1 specificity pocket of thrombin using flexible and constrained amidines. The most active compound of this class is 11 with Ki = 69 nM, which is ca. 15-f...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu T,Tomczuk B,Bone R,Murphy L,Salemme FR,Soll RM

更新日期：2000-01-03 00:00:00

abstract：:A series of novel pyrimido[1,2-b]indazoles 5, 7 have been prepared from 3-trifluoromethyl-5-phenyl-2,6-dicyano anilines 1 via novel indazole regioisomers 3 and 4 through a facile strategy. Specific examples were evaluated for anticancer activity in vitro and found to exhibit promising activity against A-549 cell lines...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yakaiah T,Lingaiah BP,Narsaiah B,Shireesha B,Ashok Kumar B,Gururaj S,Parthasarathy T,Sridhar B

更新日期：2007-06-15 00:00:00

abstract：:We have developed a new series of progesterone receptor modulators based upon the 4-aryl-phenylsulfonamide. Initial work in the series afforded potent compounds with good properties, however an advanced intermediate proved to be genotoxic in a non-GLP Ames assay following metabolic activation. We subsequently solved t...

journal_title：Bioorganic & medicinal chemistry letters

authors： McComas C,Cohen J,Huselton C,Marella M,Melenski E,Mugford C,Slayden O,Winneker R,Wrobel J,Yudt MR,Fensome A

更新日期：2012-12-01 00:00:00

abstract：:A series of 5-substitutedbenzylideneamino-2-butylbenzofuran-3-yl-4-methoxyphenyl methanones is synthesized and evaluated for antileishmanial and antioxidant activities. Compounds 4f (IC50 = 52.0 ± 0.09 µg/ml), 4h (IC50 = 56.0 ± 0.71 µg/ml) and 4l (IC50 = 59.3 ± 0.55 µg/ml) were shown significant antileishmanial when c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patil SR,Bollikonda S,Patil RH,Sangshetti JN,Bobade AS,Asrondkar A,Reddy PP,Shinde DB

更新日期：2018-02-01 00:00:00

abstract：:The discovery of 2-acylamino-2-phenylethyl disodium phosphates and as structurally novel inhibitors of TNF-alpha production is reported. Structure-activity relationships (SARs) are also discussed. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matsui T,Kondo T,Nishita Y,Itadani S,Nakatani S,Omawari N,Sakai M,Nakazawa S,Ogata A,Ohno H,Obata T,Nakai H,Toda M

更新日期：2002-03-25 00:00:00

abstract：:Novel conformationally-restricted mTOR kinase inhibitors with cyclic sulfone scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the mTOR potency and selectivity against class I PI3Kα kinase. PF-05139962 was identified with excellent mTOR b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu KK,Bailey S,Dinh DM,Lam H,Li C,Wells PA,Yin MJ,Zou A

更新日期：2012-08-01 00:00:00

abstract：:Naphthalimide-derived azoles as a new type of antimicrobial agents were synthesized and evaluated for their efficiency in vitro against eight bacteria and two fungi by two fold serial dilution technique. Most title compounds exhibited good antimicrobial potency with low MIC values ranging from 1 to 16μg/mL. Notably, s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang YY,Zhou CH

更新日期：2011-07-15 00:00:00

abstract：:We have synthesized 3 analogs of the dopamine D2 receptor (D2 DR) antagonist spiperone that can be conjugated to streptavidin-coated quantum dots via a pegylated biotin derivative. Using fluorescent imaging we demonstrate that substitution on the spiro position is tolerated, whilst the length and rigidity of a spacer ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tomlinson ID,Kovtun O,Crescentini TM,Rosenthal SJ

更新日期：2019-04-15 00:00:00

abstract：:Kynurenine monooxygenase (KMO) is a potential drug target for treatment of neurodegenerative disorders such as Huntington's and Alzheimer's diseases. We have evaluated substituted kynurenines as substrates or inhibitors of KMO from Cytophaga hutchinsonii. Kynurenines substituted with a halogen at the 5-position are ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Phillips RS,Anderson AD,Gentry HG,Güner OF,Bowen JP

更新日期：2017-04-15 00:00:00

abstract：:A series of 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC(50) values for inhibition of 5-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hansen FK,Khankischpur M,Tolaymat I,Mesaros R,Dannhardt G,Geffken D

更新日期：2012-08-01 00:00:00

abstract：:We describe an efficient method for the synthesis of alkyl lysophosphatidic acid (LPA) analogs as well as alkyl LPA mono- and difluoromethylene phosphonate analogs. Each alkyl LPA analog was evaluated for subtype-specific LPA receptor agonist activity using a cell migration assay for LPA(1) activation in cancer cells ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y,Tanaka M,Arai H,Aoki J,Prestwich GD

更新日期：2004-11-01 00:00:00

abstract：:Hydrolysis of beta-lactam antibiotics by beta-lactamases (e.g., metallo-beta-lactamase, mbetal) is one of the major bacterial defense systems. These enzymes can catalyze the hydrolysis of a variety of antibiotics including the latest generation of cephalosporins, cephamycins and imipenem. It is shown in this paper tha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tamilselvi A,Mugesh G

更新日期：2010-06-15 00:00:00

abstract：:Among a series of taxinine (1) and its designed derivatives (2-33), two taxoids (29 and 33) increased cellular accumulation of vincristine in multidrug-resistant tumor cells more potently than verapamil, while the activities of eight taxoids (11, 14-16, 22, and 30-32) were comparable with that of verapamil. These resu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hosoyama H,Shigemori H,Tomida A,Tsuruo T,Kobayashi J

更新日期：1999-02-08 00:00:00

abstract：:A series of conformationally restricted bis-azaaromatic quaternary ammonium salts (3 and 4) have been designed and synthesized in order to investigate the possible binding conformations of N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB; 2), a compound which potently inhibits neuronal nicotinic acetylcholin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng G,Zhang Z,Pivavarchyk M,Deaciuc AG,Dwoskin LP,Crooks PA

更新日期：2007-12-15 00:00:00

abstract：:The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure-activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kobayashi K,Uchiyama M,Ito H,Takahashi H,Yoshizumi T,Sakoh H,Nagatomi Y,Asai M,Miyazoe H,Tsujita T,Hirayama M,Ozaki S,Tani T,Ishii Y,Ohta H,Okamoto O

更新日期：2009-07-01 00:00:00

abstract：:The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vasudevan A,Conner SE,Gentles RG,Faghih R,Liu H,Dwight W,Ireland L,Kang CH,Esbenshade TA,Bennani YL,Hancock AA

更新日期：2002-11-04 00:00:00

abstract：:The elongation condensing enzymes in the bacterial fatty acid biosynthesis pathway represent desirable targets for the design of novel, broad-spectrum antimicrobial agents. A series of substituted benzoxazolinones was identified in this study as a novel class of elongation condensing enzyme (FabB and FabF) inhibitors ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng Z,Parsons JB,Tangallapally R,Zhang W,Rock CO,Lee RE

更新日期：2014-06-01 00:00:00

abstract：:KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang S,Lu D,Ouyang P

更新日期：2018-09-15 00:00:00

abstract：:New antimicrobial compounds are of major importance because of the growing problem of bacterial resistance and antimicrobial peptides have been gaining a lot of interest. Their mechanism of action, however, is often obscure. Here a set of non-peptidic compounds with antimicrobial activity are presented that have been ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Appelt C,Schrey AK,Söderhäll JA,Schmieder P

更新日期：2007-04-15 00:00:00

abstract：:A selection of 76 nitroheterocycles and related compounds from our in-house compound library was screened in vitro against the parasite Trypanosoma brucei rhodesiense, causative agent of human African trypanosomiasis (HAT). The unspecific cytotoxicity of the compounds was also evaluated against rat myoblast L6-cells t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arán VJ,Kaiser M,Dardonville C

更新日期：2012-07-15 00:00:00

abstract：:A series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines, mu opioid receptor antagonists, analogs of alvimopan, were prepared using solid phase methodology. This study led to the identification of a highly selective mu opioid receptor antagonist, which interacts selectively with mu peripheral recept...

journal_title：Bioorganic & medicinal chemistry letters

authors： Le Bourdonnec B,Barker WM,Belanger S,Wiant DD,Conway-James NC,Cassel JA,O'Neill TJ,Little PJ,DeHaven RN,DeHaven-Hudkins DL,Dolle RE

更新日期：2008-03-15 00:00:00

abstract：:A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure-activity relationships (SARs) of this novel class of arylthiourea derivatives that show...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang IJ,Wang LW,Hsu SJ,Lee CC,Lee YC,Wu YS,Yueh A,Wang JC,Hsu TA,Chao YS,Chern JH

更新日期：2009-11-01 00:00:00

abstract：:Analogues of the benzazepine dopamine D1 receptor antagonist SCH-23390 incorporating the cyclo-pentadienyltricarbonyl-rhenium (CPTR) moiety were synthesized and evaluated pharmacologically. The CPTR derivatives retained affinity (0.3-2.9 nM) and D1 selectivity of the parent compound, supporting their use as neuropharm...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tamagnan G,Baldwin RM,Kula NS,Baldessarini RJ,Innis RB

更新日期：2000-05-15 00:00:00

abstract：:A new series of imidazopyridine CB2 agonists is described. Structural optimization improved CB2/CB1 selectivity in this series and conferred physical properties that facilitated high in vivo exposure, both centrally and peripherally. Administration of a highly selective CB2 agonist in a rat model of analgesia was inef...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trotter BW,Nanda KK,Burgey CS,Potteiger CM,Deng JZ,Green AI,Hartnett JC,Kett NR,Wu Z,Henze DA,Della Penna K,Desai R,Leitl MD,Lemaire W,White RB,Yeh S,Urban MO,Kane SA,Hartman GD,Bilodeau MT

更新日期：2011-04-15 00:00:00

abstract：:Selective metabotropic glutamate receptor 2 (mGluR2) inhibitors have been demonstrated to show therapeutic effects by improving alleviating symptoms of schizophrenic patients in clinical studies. Herein we report the synthesis and preliminary evaluation of a 11C-labeled positron emission tomography (PET) tracer origin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumata K,Zhang Y,Ogawa M,Kurihara Y,Mori W,Hu K,Fujinaga M,Nengaki N,Zhang MR

更新日期：2020-12-01 00:00:00

abstract：:A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA with selectivity over tPA and plasmin. Potency is enhanced by the presence of a 4-halo and a 7-aryl substituent, particularly when substituted by a 3-carboxylic acid group. Compound 13j (UK-356,202) combines excellent potency and selectivit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barber CG,Dickinson RP,Fish PV

更新日期：2004-06-21 00:00:00

abstract：:Docking studies of 4-phenylthiazolinethione on human IDO1 suggest complexation of the heme iron by the exocyclic sulfur atom further reinforced by hydrophobic interactions of the phenyl ring within pocket A of the enzyme. On this basis, chemical modifications were proposed to increase inhibition activity. Synthetic ro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Balti M,Plas A,Meinguet C,Haufroid M,Thémans Q,Efrit ML,Wouters J,Lanners S

更新日期：2017-08-01 00:00:00

abstract：:Novel arylthiomethyl morpholines are potent selective norepinephrine reuptake inhibitors (NERIs) and dual serotonin/norepinephrine reuptake inhibitors (SRI/NERIs). The target compounds were prepared using a stereochemically versatile synthesis featuring an aldol condensation as the key step. One enantiomer of the 2-me...

journal_title：Bioorganic & medicinal chemistry letters

authors： Boot J,Cases M,Clark BP,Findlay J,Gallagher PT,Hayhurst L,Man T,Montalbetti C,Rathmell RE,Rudyk H,Walter MW,Whatton M,Wood V

更新日期：2005-02-01 00:00:00