abstract：:To investigate the stability of 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentafuranosylcytosine 3'-phosphoric acid, its thymidine ester was prepared via the phosphoramidite method using allyl protection for the phosphate function. This ester is stable under acidic conditions but extremely labile under basic conditions, de...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hayakawa Y,Kawai R,Otsuki K,Kataoka M,Matsuda A

更新日期：1998-09-22 00:00:00

abstract：:A new generation of propylene-spaced fluorous allyltin reagents [(Rf(CH2)3)3SnCH2CH = CH2] is described. These succeed in radical allylations where their lower homologs (ethylene-spaced) fail, and they provide improved performance in transition metal catalyzed allylations. The reagents and byproducts are readily separ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Curran DP,Luo Z,Degenkolb P

更新日期：1998-09-08 00:00:00

abstract：:A combinatorial synthesis process involving sequential cycles of cutting a membrane support into pieces and combining these into groups and subjecting the groups to simultaneous solid-phase chemical reactions is demonstrated by the rapid assembly of four hundred N-terminally biotinylated, soluble, octameric peptide po...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dittrich F,Tegge W,Frank R

更新日期：1998-09-08 00:00:00

abstract：:The reaction between methanethiosulfonate reagents and cysteine mutants of subtilisin is quantitative and can be used to prepare chemically modified mutant enzymes (CMMs) with novel properties. The virtually unrestricted structural variations possible for CMMs presents a preparative and screening challenge. To address...

journal_title：Bioorganic & medicinal chemistry letters

authors： Plettner E,Khumtaveeporn K,Shang X,Jones JB

更新日期：1998-09-08 00:00:00

abstract：:The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Buckman BO,Mohan R,Koovakkat S,Liang A,Trinh L,Morrissey MM

更新日期：1998-08-18 00:00:00

abstract：:A series of the titled compounds was synthesized and tested for anti-Helicobacter pylori activities. We discovered Y-34867 having the most potent activity against Helicobacter pylori among the quinolones tested along with high photostability. Furthermore, Y-34867 showed an excellent therapeutic effect in the experimen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sakurai N,Sano M,Hirayama F,Kuroda T,Uemori S,Moriguchi A,Yamamoto K,Ikeda Y,Kawakita T

更新日期：1998-08-18 00:00:00

abstract：:Based on the findings that cholest-4-en-3-one, an intestinal metabolite of cholesterol, has an anti-obesity effect on animals, the structure-effect relationship of its 3-oxo derivatives and related compounds were investigated. Cholesten-3-ones, which possesses an enone structure with a carbonyl group at C3, markedly i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suzuki K,Shimizu T,Nakata T

更新日期：1998-08-18 00:00:00

abstract：:The in vitro antithrombotic activity of synthetic glycoconjugates I and II, comprising a flexible polyethylene glycol type and a rigid polyglucose type spacer, respectively, are compared to heparin. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dreef-Tromp CM,Basten JE,Broekhoven MA,van Dinther TG,Petitou M,van Boeckel CA

更新日期：1998-08-18 00:00:00

abstract：:Novel Leu-enkephalin (Leu-Enk) (1) analogs possessing various types of alpha-substituted serine instead of its glycine residue in the position 2 were synthesized via an efficient O,N-migration method. The binding characteristics of the synthetic analogs using Chinese hamster ovary (CHO) cells expressed cloned rat mu-,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Horikawa M,Shigeri Y,Yumoto N,Yoshikawa S,Nakajima T,Ohfune Y

更新日期：1998-08-04 00:00:00

abstract：:All the stereoisomers of 2-(2-carboxy-3,3-difluorocyclopropyl)glycines (F2CCGs) were synthesized in enantiomerically pure forms using (R)-2,3-O-isopropyl-ideneglyceraldehyde as a chiral precursor. L-F2CCG-I, one of the stereoisomers corresponding to an extended form of L-glutamate was found to be a potent agonist for ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shibuya A,Sato A,Taguchi T

更新日期：1998-08-04 00:00:00

abstract：:This SAR study has shown that the salicylanilide is the pharmacophore for inhibition of the bacterial two-component system. Hydrophobic substituents improve the potency of inhibitors in this series; however, hydrophobicity is not the sole determinant for inhibition; structural and electronic requirements also exist. C...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hlasta DJ,Demers JP,Foleno BD,Fraga-Spano SA,Guan J,Hilliard JJ,Macielag MJ,Ohemeng KA,Sheppard CM,Sui Z,Webb GC,Weidner-Wells MA,Werblood H,Barrett JF

更新日期：1998-07-21 00:00:00

abstract：:Prodrug esters of the indolocarbazole CEP-751 (KT-6587) were prepared with the goal of identifying water soluble, stable but cleavable forms for intravenous dosing. A dipeptide proform Lys-beta-Ala (16, CEP-2563/KT-8391) was identified for advancement to clinical trials. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hudkins RL,Iqbal M,Park CH,Goldstein J,Herman JL,Shek E,Murakata C,Mallamo JP

更新日期：1998-07-21 00:00:00

abstract：:Homology modeling of candida lanosterol C-14 demethylase, synthesis and in vitro antifungal activities of cyclohexyl analogs of restricticin are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tsukuda T,Shiratori Y,Watanabe M,Ontsuka H,Hattori K,Shirai M,Shimma N

更新日期：1998-07-21 00:00:00

abstract：:The title compound was prepared by enzymatic transfer of oligosaccharide to a synthetic pentapeptide containing the Glc-Asn linkage. The compound was not hydrolyzed by glycoamidases from plant and bacterial sources, but it inhibited both enzymes in the micromolar range. Its activity is compared to other potential inhi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deras IL,Takegawa K,Kondo A,Kato I,Lee YC

更新日期：1998-07-07 00:00:00

abstract：:Betulinic acid has been modified at C-3, C-20, and C-28 positions and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. This preliminary investigation demonstrates that simple modifications of the parent structure of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim DS,Pezzuto JM,Pisha E

更新日期：1998-07-07 00:00:00

abstract：:A combinatorial peptidomimetic library containing diversified alpha-methylated amino acids was generated by the Ugi four component condensation (4cc) reaction from acids, amines, isocyanides and ketones in both solution and solid phase synthetic procedures. This one-pot methodology overall gave fair to good yields, wh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim SW,Shin YS,Ro S

更新日期：1998-07-07 00:00:00

abstract：:Based on the structures of aminopyridine thrombin inhibitors (1), a series of aminoalkyl- and guanidinoalkyl-substituted diarylsulfonamides were prepared. The most potent derivative, N-[3-(4-guanidinobutoxy)-5-methyl-phenyl]-benzenesulfonamide (6c) had Ki = 0.18 microM for thrombin and did not inhibit trypsin, plasmin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weber IR,Neidlein R,von der Saal W,Grams F,Leinert H,Strein K,Engh RA,Kucznierz R

更新日期：1998-07-07 00:00:00

abstract：:A new class of non-ionic amphiphilic molecules suitable for biological purposes, especially extraction of membrane proteins, is reported. Such surfactants were prepared in two steps: addition of alkyl or fluoroalkyl mercaptan on Tris(hydroxymethyl)acrylamidomethane (THAM) derivatives, followed by the oxydation of sulf...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barthélémy P,Maurizis JC,Lacombe JM,Pucci B

更新日期：1998-06-16 00:00:00

abstract：:A series of potent specific HIV-1 RT inhibitory compounds is described. The compounds are urea analogs of PETT (PhenylEthylThiazoleThiourea) derivatives and the series includes derivatives with an ethyl linker (1-6) and conformationally restricted analogs (7-13). The antiviral activity is determined both at the RT lev...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sahlberg C,Noréen R,Engelhardt P,Högberg M,Kangasmetsä J,Vrang L,Zhang H

更新日期：1998-06-16 00:00:00

abstract：:Novel dihydroalkoxybenzyloxopyrimidine (S-DABO) derivatives targeting the non-nucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been synthesized using a novel computer model for the NNI binding pocket and tested for their RT inhibitory activity in cell-free a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vig R,Mao C,Venkatachalam TK,Tuel-Ahlgren L,Sudbeck EA,Uckun FM

更新日期：1998-06-16 00:00:00

abstract：:Monocyclic beta-lactams have been identified as potent and selective inhibitors of the human cytomegalovirus protease (HCMV) N(o). Two series of these inhibitors are described, a peptidyl series of compounds and non-peptidic molecules featuring lower molecular weights. The SAR work that lead to the discovery of these ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Déziel R,Malenfant E

更新日期：1998-06-02 00:00:00

abstract：:A pyridine group was linked to the tetrahydronaphthalene moiety of the derivatives described in the preceding paper, to afford new combined thromboxane receptor (TP-receptor) antagonists and synthase inhibitors. The most interesting compound 2f inhibits TXA2 synthase with an IC50 value of 0.64 microM and the aggregati...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cimetière B,Dubuffet T,Landras C,Descombes JJ,Simonet S,Verbeuren TJ,Lavielle G

更新日期：1998-06-02 00:00:00

abstract：:Cross-linkage of the branches of poly(ethylenimine) (PEI) suppresses flexibility of the polymer as revealed by decreased affinity of the amino groups on PEI backbone towards proton or Ni(II) ion. The cross-linkage improves ability of the PEI derivative equipped with beta-cyclodextrin to deacylate an ester containing t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suh J,Noh YS

更新日期：1998-06-02 00:00:00

abstract：:3-O-tert-Butyldimethylsilyl-17 alpha-(6-mesyloxyhexynyl)estradiol was converted to the azide in 60-70% yield with NaN3/DMPU, then reduced to the corresponding amine (> 95% yield). Acylation with the N-hydroxysuccinimide esters of biotin, 5-carboxyfluorescein and 10-(3-sulfopropyl)-N-tosyl-N-(3- carboxypropyl)acridiniu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adamczyk M,Chen YY,Moore JA,Mattingly PG

更新日期：1998-06-02 00:00:00

abstract：:The isopolar nonisosteric phosphonate analogs of ApA differing in the position of extra methylene group introduced into the sugar-phosphate backbone, featuring both possible 2',5'- and 3',5'- pairs as well as their conformationally restricted congeners, were investigated for their ability to form complexes with polyU....

journal_title：Bioorganic & medicinal chemistry letters

authors： Pressová M,Endová M,Toĉík Z,Liboska R,Rosenberg I

更新日期：1998-05-19 00:00:00

abstract：:In order to establish structural elements responsible for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi by 2-aminodiphenylsulfides, a series of dissymmetrical derivatives, corresponding to the replacement of one aromatic moiety by different amines, was synthesized. TR inhibition studies revealed th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Girault S,Davioud-Charvet E,Salmon L,Berecibar A,Debreu MA,Sergheraert C

更新日期：1998-05-19 00:00:00

abstract：:A novel solid-phase synthesis of 5'-radiolabeled oligonucleotides is described. The labeling reaction is carried out by the phosphoramidite method with the aid of [4,6-di-14C]-5'-dimethoxytritylthymidine building block 1. The feasibility of the method is demonstrated by preparation of 3'-phosphorylated dodecathymidyla...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guzaev A,Boyode B,Balow G,Tivel KL,Manoharan M

更新日期：1998-05-05 00:00:00

abstract：:Perfluorination of phthalimides leads to dramatically increased potency as inhibitors of TNF-alpha production. We examined the enantiodependence for several tetrafluorophthalimides and alpha-methylthalidomide, 3. Only 3 exhibited strikingly enantiodependent activity. The key structural determinant for the enhanced act...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niwayama S,Loh C,Turk BE,Liu JO,Miyachi H,Hashimoto Y

更新日期：1998-05-05 00:00:00

abstract：:New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sasaki S,Hashimoto T,Obana N,Yasuda H,Uehara Y,Maeda M

更新日期：1998-05-05 00:00:00

abstract：:Pyridone-based peptidomimetic inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with an aminomethylene ketone activating group in the P1' position are described. Several analogues with sub-nanomolar Ki's versus ICE and improved aqueous solubility are reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Semple G,Ashworth DM,Batt AR,Baxter AJ,Benzies DW,Elliot LH,Evans DM,Franklin RJ,Hudson P,Jenkins PD,Pitt GR,Rooker DP,Yamamoto S,Isomura Y

更新日期：1998-04-21 00:00:00

abstract：:A series of leinamycin derivatives were synthesized and evaluated for antitumor activity. Modifications at C-8 and C-9 positions revealed a broad structure-activity relationship in vitro and some derivatives showed potent antiproliferative activity against HeLa S3 cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kanda Y,Ashizawa T,Saitoh Y,Saito H,Gomi K,Okabe M

更新日期：1998-04-21 00:00:00

abstract：:A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 microM as an inhibi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cushman M,Insaf S,Ruell JA,Schaeffer CA,Rice WG

更新日期：1998-04-07 00:00:00

abstract：:Substituted pyrazoles, 1,2,4-triazoles, and tetrazoles are good surrogates for cis-amide bonds in a series of boronate ester thrombin inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duncia JV,Santella JB 3rd,Higley CA,VanAtten MK,Weber PC,Alexander RS,Kettner CA,Pruitt JR,Liauw AY,Quan ML,Knabb RM,Wexler RR

更新日期：1998-04-07 00:00:00

abstract：:A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sanner MA,Chappie TA,Dunaiskis AR,Fliri AF,Desai KA,Zorn SH,Jackson ER,Johnson CG,Morrone JM,Seymour PA,Majchrzak MJ,Faraci WS,Collins JL,Duignan DB,Prete Di CC,Lee JS,Trozzi A

更新日期：1998-04-07 00:00:00

abstract：:In the search for spin labelled intercalators of general use to construct DNA-binding conjugates, 6-chloro-2-[(1-oxyl-2,2,5,5-tetramethyl- pyrrolin-3-yl)methyloxy]-9-phenoxy-acridine 5, has been prepared. This key-intermediate reacts with amines to give the corresponding labelled 9-amino substituted acridines. Compara...

journal_title：Bioorganic & medicinal chemistry letters

authors： Belmont P,Chapelle C,Demeunynck M,Michon J,Michon P,Lhomme J

更新日期：1998-03-17 00:00:00

abstract：:2-Octyl gamma-bromoacetoacetate (O gamma Br), an endogenous compound originally isolated from human cerebrospinal fluid (CSF), has previously been demonstrated to increase REM sleep duration in cats. Based on the chemical structure of O gamma Br and its reported sleep-inducing effects, we synthesized O gamma Br along ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patricelli MP,Patterson JE,Boger DL,Cravatt BF

更新日期：1998-03-17 00:00:00

abstract：:A series of 2-phenylbenzofuran derivatives with a diphenylmethylcarbamoyl group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities in vitro. They had inhibitory activities against both enzymes and the 6-carbamoyl derivativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishibashi K,Nakajima K,Sugioka Y,Sugiyama M,Hamada T,Horikoshi H,Nishi T

更新日期：1998-03-17 00:00:00

abstract：:Oligonucleotides consisting of 2'-deoxy-2'(S)-ethinyl-thymidine,-uridine, and -adenosine have been prepared. Whereas the modified pyrimidine oligonucleotides uniformly lead to weaker pairing affinity with DNA and RNA complements, the corresponding adenine oligonucleotides show enhanced thermal stability in duplexes wi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Buff R,Hunziker J

更新日期：1998-03-03 00:00:00

abstract：:Functionalized 1,3-teraryls, synthesized through ring transformation of 6-aryl-3-carbomethoxy-4-methylthio-2H-pyran-2-one from arylketone have been screened for their hepatoprotective activity and of them have demonstrated significant protection in animal model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ram VJ,Goel A,Patnaik GK

更新日期：1998-03-03 00:00:00

abstract：:Based on the recently resolved crystal structure of complex (-)-huperzine A-AChE, we simulated the interaction between (-)-huperzine A analogues and AChE using molecular dynamics method. It was revealed that the methyl group at the three carbon bridge of (-)-huperzine A can form a weak hydrogen bond with the phenol hy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu DX,Jiang H,Wang QM,Chen KX,Ji RY

更新日期：1998-03-03 00:00:00