Promoting the formation of tetramolecular G-quadruplexes under freezing condition.

abstract：:Herein we report 6-ethoxy-6-oxo-5-(2-phenylhydrazono) hexanoic acid and 3-(2-carboxyethyl)-1H-indole-2-carboxylic acid derivatives as synthetically accessible leads for human kynurenine aminotransferase-I (KAT-I) inhibitors. In total, 12 compounds were synthesized and their biological activities were determined using ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Akladios FN,Nadvi NA,Park J,Hanrahan JR,Kapoor V,Gorrell MD,Church WB

更新日期：2012-02-15 00:00:00

abstract：:The reduced activation of PPARs has a positive impact on cancer cell growth and viability in multiple preclinical tumor models, suggesting a new therapeutic potential for PPAR antagonists. In the present study, the benzothiazole amides 2a-g were synthesized and their activities on PPARs were investigated. Transactivat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ammazzalorso A,De Lellis L,Florio R,Laghezza A,De Filippis B,Fantacuzzi M,Giampietro L,Maccallini C,Tortorella P,Veschi S,Loiodice F,Cama A,Amoroso R

更新日期：2019-08-15 00:00:00

abstract：:Inhibitors of CYP1 enzymes may play vital roles in the prevention of cancer and overcoming chemo-resistance to anticancer drugs. In this letter, we report synthesis of twenty-three pyrrole based heterocyclic chalcones which were screened for inhibition of CYP1 isoforms. Compound 3n potently inhibited CYP1B1 with an IC...

journal_title：Bioorganic & medicinal chemistry letters

authors： Williams IS,Joshi P,Gatchie L,Sharma M,Satti NK,Vishwakarma RA,Chaudhuri B,Bharate SB

更新日期：2017-08-15 00:00:00

abstract：:The HIV-1 envelope glycoprotein gp41 fusion intermediate is a promising drug target for inhibiting viral entry. However, drug development has been impeded by challenges inherent in mediating the underlying protein-protein interaction. Here we report on the identification of fragments that bind to a C-terminal sub-pock...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu S,Gochin M

更新日期：2013-09-15 00:00:00

abstract：:Cage amines 1-4 are potent peripheral anionic site-bound reversible inhibitors of both acetylcholinesterase and butyrylcholinesterase. Cage amines 1-3 are selective butyrylcholinesterase inhibitor versus acetylcholinesterase. For both enzymes, the -log K(i) values linearly correlate with the difference of substituted ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lin G,Tsai HJ,Tsai YH

更新日期：2003-09-01 00:00:00

abstract：:A series of heterobiaryl amides was designed and synthesized as novel mGluR5 antagonists. The synthesis using palladium catalyzed Suzuki-Miyaura cross-coupling reactions provided an array of compounds with a range of in vitro activities. In particular, compound 9e, 4(3,5-difluorophenyl)-N-(6-methylpyridin-1-yl)picolin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kulkarni SS,Newman AH

更新日期：2007-04-01 00:00:00

abstract：:The structure of the S1P2 antagonist 1 has been modified with the aim of improving its oral bioavailability. The chemical modification of the alkyl chain and carboxylic acid moieties of 1 led to significant improvements in the oral exposure of compounds belonging to this series. The optimization of the ring size of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kusumi K,Shinozaki K,Yamaura Y,Hashimoto A,Kurata H,Naganawa A,Otsuki K,Matsushita T,Sekiguchi T,Kakuuchi A,Yamamoto H,Seko T

更新日期：2016-02-15 00:00:00

abstract：:A series of alpha1a receptor antagonists derived from a 4-aryl-3,4-dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to picomolar range along with high selectivity was obtained. In vivo efficacy in a prostate contraction model in rats was observed with a few derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nantermet PG,Barrow JC,Selnick HG,Homnick CF,Freidinger RM,Chang RS,O'Malley SS,Reiss DR,Broten TP,Ransom RW,Pettibone DJ,Olah T,Forray C

更新日期：2000-08-07 00:00:00

abstract：:Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with (S)- or (R)-benzyl glycidyl ether. The (S)-enantiomer, 11 (ABT-770), is orally bioavailable ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Curtin ML,Florjancic AS,Heyman HR,Michaelides MR,Garland RB,Holms JH,Steinman DH,Dellaria JF,Gong J,Wada CK,Guo Y,Elmore IB,Tapang P,Albert DH,Magoc TJ,Marcotte PA,Bouska JJ,Goodfellow CL,Bauch JL,Marsh KC,Morgan

更新日期：2001-06-18 00:00:00

abstract：:The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao DG,Ma YY,Peng W,Zhou AY,Zhang Y,Ding L,Du Z,Zhang K

更新日期：2016-01-01 00:00:00

abstract：:A new halicyclamine derivative, tetradehydrohalicyclamine B (1), was isolated from the marine sponge Acanthostrongylophora ingens, along with halicyclamine B (2) as proteasome inhibitors. Compound 1 is the second example found to have a pyridinium ring in the halicyclamine family. Although the relative configuration o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kato H,El-Desoky AH,Takeishi Y,Nehira T,Angkouw ED,Mangindaan REP,de Voogd NJ,Tsukamoto S

更新日期：2019-01-01 00:00:00

abstract：:New adjuvants of warfarin anticoagulant activity have been developed. These compounds, which are 1,4-methano-1,2,3,4-tetrahydroanthracene-9,10-diol derivatives, act synergistically with warfarin to potentiate its anticoagulant effect. None of the compounds tested is an effective oral anticoagulant in the absence of wa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stromich JJ,Weber AK,Mirzaei YR,Caldwell MD,Lewis DE

更新日期：2010-03-15 00:00:00

abstract：:In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry. The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads. Because the affinities of the initial fragments are often low, detection meth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Davis BJ,Erlanson DA

更新日期：2013-05-15 00:00:00

abstract：:The synthesis and pharmacological activity of novel nociceptin/orphanin FQ (N/OFQ) analogues modified in the Phe(1)-Gly(2) peptide bond are reported. The aim of the present work was to elucidate the importance of this peptide bond for the N/OFQ receptor (NOP) interaction. Our study indicates that the first peptide bon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guerrini R,Rizzi D,Zucchini M,Tomatis R,Regoli D,Calo' G,Salvadori S

更新日期：2003-02-10 00:00:00

abstract：:In the past half century research efforts have defined a critical role for angiogenesis in tumor growth and metastasis. We previously reported that inhibition of a novel target, ENOX1, by a (Z)-2-benzylindol-3-ylmethylene) quinuclidin-3-ol, suppressed tumor angiogenesis. The present study was undertaken in order to es...

journal_title：Bioorganic & medicinal chemistry letters

authors： Venkateswaran A,Reddy YT,Sonar VN,Muthusamy V,Crooks PA,Freeman ML,Sekhar KR

更新日期：2010-12-15 00:00:00

abstract：:Benzothiazole benzimidazole (S)-isothiazolidinone ((S)-IZD) derivatives 5 were discovered through a peptidomimetic modification of the tripeptide (S)-IZD protein tyrosine phosphatase 1B (PTP1B) inhibitor 1. These derivatives are potent, competitive, and reversible inhibitors of PTP1B with improved caco-2 permeability....

journal_title：Bioorganic & medicinal chemistry letters

authors： Sparks RB,Polam P,Zhu W,Crawley ML,Takvorian A,McLaughlin E,Wei M,Ala PJ,Gonneville L,Taylor N,Li Y,Wynn R,Burn TC,Liu PC,Combs AP

更新日期：2007-02-01 00:00:00

abstract：:The synthesis of racemic tetrahydrocurcumin- (THC-), tetrahydrodemethoxycurcumin- (THDC-) and tetrahydrobisdemethoxycurcumin- (THBDC-) dihydropyrimidinone (DHPM) analogues was achieved by utilizing the multi-component Biginelli reaction in the presence of copper sulphate as a catalyst. The evaluation of acetylcholines...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arunkhamkaew S,Athipornchai A,Apiratikul N,Suksamrarn A,Ajavakom V

更新日期：2013-05-15 00:00:00

abstract：:From an easily available partially protected formal derivative of 1-deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful β-d-galactosidase inhibitor 4-epi-isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thonhofer M,Weber P,Santana AG,Fischer R,Pabst BM,Paschke E,Schalli M,Stütz AE,Tschernutter M,Windischhofer W,Withers SG

更新日期：2016-03-01 00:00:00

abstract：:6-Arylamino-5,8-quinolinediones 3 and 7-arylamino-5,8-isoquinolinediones 4 were synthesized as inhibitors of endothelium-dependent vasorelaxation. The quinones inhibited the vasorelaxation of rat aorta with the endothelium. Among them, the quinones 3a, 3b, 3f, 4b, 4d and 4g strongly inhibited the vasorelaxation. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ryu CK,Jung SH,Lee JA,Kim HJ,Lee SH,Chung JH

更新日期：1999-09-06 00:00:00

abstract：:The piperidyl and prolyl amides of Kemp's triacid (7 and 8, respectively) have been prepared and their rates of intramolecular acylolysis measured as a function of pD. The piperidyl derivative 7 reacts approximately four-times faster (e.g., t(1/2)=3 min at 20 degrees C and pD7.7) than the previously reported pyrrolidy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dougan ML,Chin JL,Solt K,Hansen DE

更新日期：2004-08-16 00:00:00

abstract：:VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has proved to be a promising target for the development of therapeutics for the treatment of a variety of human cancers. Here, we report the first example of a successful application of the structure-based virtual screening to identify novel BRAF inhibitors...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park H,Choi H,Hong S,Hong S

更新日期：2011-10-01 00:00:00

abstract：:Multiple regions of the 3-oxazolidinedione-6-naphthyl-pyridinone series identified via high throughput screening were explored. SAR studies of these regions including the left-hand side oxazolidinedione moiety, α-substituent on the oxazolidinedione ring, central pyridinone core, and substituents on the central pyridin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morales-Ramos ÁI,Li YH,Hilfiker M,Mecom JS,Eidam P,Shi D,Tseng PS,Brooks C,Zhang D,Wang N,Jaworski JP,Morrow D,Fries H,Edwards R,Jin J

更新日期：2011-05-15 00:00:00

abstract：:Screening of the Maybridge compound collection identified 4-arylphthalazinones as micromolar inhibitors of PARP-1 catalytic activity. Subsequent optimisation of both inhibitory activity and metabolic stability led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-ones with low nanomolar, cellular activity...

journal_title：Bioorganic & medicinal chemistry letters

authors： Loh VM Jr,Cockcroft XL,Dillon KJ,Dixon L,Drzewiecki J,Eversley PJ,Gomez S,Hoare J,Kerrigan F,Matthews IT,Menear KA,Martin NM,Newton RF,Paul J,Smith GC,Vile J,Whittle AJ

更新日期：2005-05-02 00:00:00

abstract：:New chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives have been synthesized by domino aldol-type reaction/hetero Diels-Alder reaction generated from o-quinone methide in situ from 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones with resorcinols/naphthols in the presenc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Madda J,Venkatesham A,Naveen Kumar B,Nagaiah K,Sujitha P,Ganesh Kumar C,Rao TP,Jagadeesh Babu N

更新日期：2014-09-15 00:00:00

abstract：:A series of analogs of GLP-1(7-36) amide containing a Nepsilon-(2-[2-[2-(3-maleimidopropylamido)ethoxy]ethoxy]acetyl)lysine has been synthesized and the resulting derivatives were bioconjugated to Cys34 of human serum albumin (HSA). The GLP-1-HSA bioconjugates were analyzed in vitro to assess the stabilizing effect of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Léger R,Thibaudeau K,Robitaille M,Quraishi O,van Wyk P,Bousquet-Gagnon N,Carette J,Castaigne JP,Bridon DP

更新日期：2004-09-06 00:00:00

abstract：:A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dhar TG,Shen Z,Gu HH,Chen P,Norris D,Watterson SH,Ballentine SK,Fleener CA,Rouleau KA,Barrish JC,Townsend R,Hollenbaugh DL,Iwanowicz EJ

更新日期：2003-10-20 00:00:00

abstract：:A series of thiazole bearing thiazolidin-4-one was discovered via high-throughput screening as non-competitive inhibitors of ADAMTS-5. Compound 31 appeared to give the best ADAMTS-5 inhibition and good selectivity over other metalloproteases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Atobe M,Maekawara N,Ishiguro N,Sogame S,Suenaga Y,Kawanishi M,Suzuki H,Jinno N,Tanaka E,Miyoshi S

更新日期：2013-04-01 00:00:00

abstract：:The identification of a novel series of PKCθ inhibitors and subsequent optimization using docking based on a crystal structure of PKCθ is described. SAR was rapidly generated around an amino pyridine-ketone hit; (6-aminopyridin-2-yl)(2-aminopyridin-3-yl)methanone 2 leading to compound 21 which significantly inhibits p...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jimenez JM,Davis C,Boyall D,Fraysse D,Knegtel R,Settimo L,Young S,Bolton C,Chiu P,Curnock A,Rasmussen R,Tanner A,Ager I

更新日期：2012-07-15 00:00:00

abstract：:Valosin-containing protein (VCP; also known as p97) is a member of the AAA ATPase family with a central role in the ubiquitin-degradation of misfolded proteins. VCP also exhibits antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. We have discovered that 2-anilino-4-aryl-1...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bursavich MG,Parker DP,Willardsen JA,Gao ZH,Davis T,Ostanin K,Robinson R,Peterson A,Cimbora DM,Zhu JF,Richards B

更新日期：2010-03-01 00:00:00

abstract：:We screened 1434 small heterocyclic molecules and identified thirteen 2,3,6-trisubstituted quinoxaline derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cell proliferation. In the screen, some of the hit compounds such as the ethylene group-coupled quinoxaline derivatives were shown to hold pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee SB,Park YI,Dong MS,Gong YD

更新日期：2010-10-01 00:00:00