Synthesis and preliminary pharmacological evaluation of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides as novel atypical antipsychotic agents.


:A series of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized by either microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H NMR, and MS) and the purity was ascertained by microanalysis. All the synthesized compounds were screened for their in vivo pharmacological activity in Swiss albino mice. D(2) antagonism studies were performed using climbing mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy. AG 3 was found to be the most active compound.


Bioorg Med Chem Lett


Sekhar KV,Rao VS,Devambatla RKV,Kumar MM




Has Abstract


2008-12-01 00:00:00














  • Discovery of a novel class of triazolones as checkpoint kinase inhibitors--hit to lead exploration.

    abstract::Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of these hits to provide a lead series is described. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Oza V,Ashwell S,Brassil P,Breed J,Deng C,Ezhuthachan J,Haye H,Horn C,Janetka J,Lyne P,Newcombe N,Otterbien L,Pass M,Read J,Roswell S,Su M,Toader D,Yu D,Yu Y,Valentine A,Webborn P,White A,Zabludoff S,Zheng X

    更新日期:2010-09-01 00:00:00

  • The synthesis of xanthones, xanthenediones, and spirobenzofurans: their antibacterial and antifungal activity.

    abstract::Exposure of the phenol, (5-bromo-2-hydroxyphenyl)(2,4,5-trimethoxyphenyl)methanone 18 to ceric ammonium nitrate (CAN) resulted in the formation of 7-bromo-3,4a-dimethoxy-2H-xanthene-2,9(4aH)-dione 19 and 5-bromo-2',5'-dimethoxy-3H-spiro[benzofuran-2,1'-cyclohexa[2,5]diene]-3,4'-dione 20. The brominated spirobenzofuran...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Omolo JJ,Johnson MM,van Vuuren SF,de Koning CB

    更新日期:2011-12-01 00:00:00

  • Preparation of alkyne-labeled 2-nitroimidazoles for identification of tumor hypoxia by Raman spectroscopy.

    abstract::Hypoxia is a characteristic feature of solid tumors. Herein, we have developed novel hypoxia-sensitive probes (IM-ACs) for Raman spectroscopic analysis, consisting of nitroimidazole as a hypoxia-targeting unit and acetylene group as the signal-emitting unit. Among IM-ACs synthesized in this study, IM-AC possessing a d...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kurihara R,Ikemura Y,Tanabe K

    更新日期:2016-10-15 00:00:00

  • Potent and selective 5-LO inhibitor bearing benzothiophene pharmacophore: discovery of MK-5286.

    abstract::The strategy and SAR studies that led to the discovery of a novel potent and orally available 5-lipoxygenase (5-LO) inhibitor 3-(4-fluorophenyl)-6-({4-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-1-benzothiophene-2-carboxamide ((S)-2l or MK-5286) were described. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Li L,Berthelette C,Chateauneuf A,Ouellet M,Sturino CF,Wang Z

    更新日期:2010-12-15 00:00:00

  • Diastereoselective synthesis of fused cyclopropyl-3-amino-2,4-oxazine β-amyloid cleaving enzyme (BACE) inhibitors and their biological evaluation.

    abstract::The diastereoselective synthesis and structure activity relationship (SAR) of a series of fused cyclopropyl-3-amino-2,4-oxazine (2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine)-containing BACE inhibitors is described. Through these efforts compound 2 was identified as a potent (cell IC50 = 15 nM) BACE inhibitor with accep...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Low JD,Bartberger MD,Cheng Y,Whittington D,Xue Q,Wood S,Allen JR,Minatti AE

    更新日期:2018-04-01 00:00:00

  • Potent and highly selective kappa opioid receptor agonists incorporating chroman- and 2,3-dihydrobenzofuran-based constraints.

    abstract::Two novel chemical classes of kappa opioid receptor agonists, chroman-2-carboxamide derivatives and 2,3-dihydrobenzofuran-2-carboxamide derivatives, were synthesized. These agents exhibited high and selective affinity for the kappa opioid receptor. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Chu GH,Gu M,Cassel JA,Belanger S,Graczyk TM,DeHaven RN,Conway-James N,Koblish M,Little PJ,DeHaven-Hudkins DL,Dolle RE

    更新日期:2005-12-01 00:00:00

  • Synthesis of morpholine derivatives using the Castagnoli-Cushman reaction as BACE1 inhibitors: Unexpected binding activity of cyclic thioamides.

    abstract::The Castagnoli-Cushman reaction between diglycolic anhydride and imines was applied for the synthesis of morpholine derivatives containing a thioamide or an amidino group. Enzyme inhibition assays towards BACE1 revealed an unexpected role of the cyclic thioamide group in providing inhibition in the micromolar range. M...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Calugi L,Lenci E,Innocenti R,Trabocchi A

    更新日期:2020-07-01 00:00:00

  • Nonpeptide oxytocin antagonists: analogs of L-371,257 with improved potency.

    abstract::Structure-activity studies on the oxytocin antagonist 1 (L-371,257; Ki = 9.3 nM) have led to the identification of a related series of compounds containing an ortho-trifluoroethoxyphenylacetyl core which are orally bioavailable and have significantly improved potency in vitro and in vivo, e.g., compound 8 (L-374,943; ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Williams PD,Bock MG,Evans BE,Freidinger RM,Gallicchio SN,Guidotti MT,Jacobson MA,Kuo MS,Levy MR,Lis EV,Michelson SR,Pawluczyk JM,Perlow DS,Pettibone DJ,Quigley AG,Reiss DR,Salvatore C,Stauffer KJ,Woyden CJ

    更新日期:1999-05-03 00:00:00

  • 2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV.

    abstract::We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Haffner CD,McDougald DL,Reister SM,Thompson BD,Conlee C,Fang J,Bass J,Lenhard JM,Croom D,Secosky-Chang MB,Tomaszek T,McConn D,Wells-Knecht K,Johnson PR

    更新日期:2005-12-01 00:00:00

  • Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.

    abstract::A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound t...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Mazzola RD Jr,Zhu Z,Sinning L,McKittrick B,Lavey B,Spitler J,Kozlowski J,Neng-Yang S,Zhou G,Guo Z,Orth P,Madison V,Sun J,Lundell D,Niu X

    更新日期:2008-11-01 00:00:00

  • The effect of 17-N substituents on the activity of the opioid κ receptor in nalfurafine derivatives.

    abstract::We have previously reported the essential structure of the opioid κ receptor agonist nalfurafine hydrochloride (TRK-820) for binding to the κ receptor. In the course of this study, we focused on the effect of the substituent at 17-N in nalfurafine on the binding affinity for the κ receptor. The exchange of the 17-N su...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Nemoto T,Yamamoto N,Wada N,Harada Y,Tomatsu M,Ishihara M,Hirayama S,Iwai T,Fujii H,Nagase H

    更新日期:2013-01-01 00:00:00

  • Assessment of new 2'-O-acetalester protecting groups for regular RNA synthesis and original 2'-modified proRNA.

    abstract::New base-labile acyloxymethyl groups were evaluated to protect 2'-OH functions of ribonucleotides for regular RNA synthesis in order to shorten the deprotection procedure upon ammonia. These same acetalester groups were assessed in 2'-modified proRNA as biolabile 2'-protections removable by cell enzymes to generate pa...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Martin AR,Lavergne T,Vasseur JJ,Debart F

    更新日期:2009-08-01 00:00:00

  • Site-specific effect of polar functional group-modification in lipids of TLR2 ligands for modulating the ligand immunostimulatory activity.

    abstract::Toll-like receptor 2 (TLR2), a member of the TLR innate immune receptor family, recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. TLR2 has a large hydrophobic pocket that recognizes long fatty acyl groups on TLR2 ligands. However, few studies have ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Arai Y,Inuki S,Fujimoto Y

    更新日期:2018-05-15 00:00:00

  • Synthesis and biological evaluation of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R).

    abstract::A novel series of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R) is reported. Members of this series have been identified, which exhibit sub-micromolar binding affinity for the MC4-R, functional potency <100nM, and good oral exposure in rat. Antagonists of the MC4-R are potentially u...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Marsilje TH,Roses JB,Calderwood EF,Stroud SG,Forsyth NE,Blackburn C,Yowe DL,Miao W,Drabic SV,Bohane MD,Daniels JS,Li P,Wu L,Patane MA,Claiborne CF

    更新日期:2004-07-16 00:00:00

  • DNA-templated click chemistry for creation of novel DNA binding molecules.

    abstract::We have developed a new methodology for producing new molecules that bind to dsDNA using DNA-templated click chemistry. The click reactions between the minor groove binding peptide and acridine intercalators were accelerated by the addition of dsDNA. Furthermore, the resulting peptide-acridine conjugate showed a sligh...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Imoto S,Hirohama T,Nagatsugi F

    更新日期:2008-10-15 00:00:00

  • Discovery of diphenyl lactam derivatives as N-type calcium channel blockers.

    abstract::A novel series of diphenyl lactam containing calcium channel blockers is described. Extensive SAR studies resulted in compounds with low molar activity and good plasma exposure after oral dosing. Compounds 2, 6 and 7 demonstrated significant efficacy in the capsaicin model of secondary hyperalgesia following oral admi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Doherty GA,Bhatia P,Vortherms TA,Marsh KC,Wetter JM,Mack H,Scott VE,Jarvis MF,Stewart AO

    更新日期:2012-02-15 00:00:00

  • Identification of a novel oxidation product from yellow fluorophore in the complex of apoPholasin and dehydrocoelenterazine.

    abstract::The complex of the recombinant fusion protein of apoPholasin and glutathione S-transferase (GST-apoPholasin) with non-fluorescent dehydrocoelenterazine (dCTZ) (GST-apoPholasin/dCTZ complex) shows yellow fluorescence at 539 nm by excitation at 430 nm. The GST-apoPholasin/dCTZ complex with a fluorophore (dCTZ*) has cons...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Inouye S,Nakamura M,Taguchi J,Hosoya T

    更新日期:2020-10-01 00:00:00

  • Discovery of 3-(trifluoromethyl)-1H-pyrazole-5-carboxamide activators of the M2 isoform of pyruvate kinase (PKM2).

    abstract::Activators of the pyruvate kinase M2 (PKM2) are currently attracting significant interest as potential anticancer therapies. They may achieve a novel antiproliferation response in cancer cells through modulation of the classic 'Warburg effect' characteristic of aberrant metabolism. In this Letter, we describe the opti...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Xu Y,Liu XH,Saunders M,Pearce S,Foulks JM,Parnell KM,Clifford A,Nix RN,Bullough J,Hendrickson TF,Wright K,McCullar MV,Kanner SB,Ho KK

    更新日期:2014-01-15 00:00:00

  • Synthesis and antiplatelet activity of gemfibrozil chiral analogues.

    abstract::The chiral analogues of gemfibrozil 5-(2,5-dimethylphenoxy)-2-methylpentanoic acid and 5-(2,5-dimethylphenoxy)-2-ethylpentanoic acid were synthesized in optically active form using (S)-4-(1-methylethyl)-2-oxazolidinone as chiral auxiliary. All compounds inhibit human platelet aggregation. From these data, one can surm...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ammazzalorso A,Amoroso R,Baraldi M,Bettoni G,Braghiroli D,De Filippis B,Duranti A,Moretti M,Tortorella P,Tricca ML,Vezzalini F

    更新日期:2002-03-11 00:00:00

  • Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and 'click' strategy.

    abstract::To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluation...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lu XF,Yang Z,Huang NY,He HB,Deng WQ,Zou K

    更新日期:2015-09-01 00:00:00

  • Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: reducing cytotoxicity by structural simplification.

    abstract::Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibit...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Fujishiro S,Dodo K,Iwasa E,Teng Y,Sohtome Y,Hamashima Y,Ito A,Yoshida M,Sodeoka M

    更新日期:2013-02-01 00:00:00

  • Design, synthesis, and pharmacological evaluation of phenoxy pyridyl derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists.

    abstract::Preclinical studies suggest that compounds with dual norepinephrine reuptake inhibitor (NRI) and 5-HT(1A) partial agonist properties may provide an important new therapeutic approach to ADHD, depression, and anxiety. Reported herein is the discovery of a novel chemical series with a favorable NRI and 5-HT(1A) partial ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dounay AB,Barta NS,Campbell BM,Coleman C,Collantes EM,Denny L,Dutta S,Gray DL,Hou D,Iyer R,Maiti SN,Ortwine DF,Probert A,Stratman NC,Subedi R,Whisman T,Xu W,Zoski K

    更新日期:2010-02-01 00:00:00

  • Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-heteroarylthiomethyldipyridodiazepinone derivatives.

    abstract::A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yoakim C,Bonneau PR,Déziel R,Doyon L,Duan J,Guse I,Landry S,Malenfant E,Naud J,Ogilvie WW,O'Meara JA,Plante R,Simoneau B,Thavonekham B,Bös M,Cordingley MG

    更新日期:2004-02-09 00:00:00

  • Biological properties of synthetic glycoconjugate mimics of heparin comprising different molecular spacers.

    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

    pub_type: 杂志文章


    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

  • Structure-activity relationships in 2-aminodiphenylsulfides against trypanothione reductase from Trypanosoma cruzi.

    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

    pub_type: 杂志文章


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

    更新日期:1998-05-19 00:00:00

  • 7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site.

    abstract::Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wang W,Devasthale P,Wang A,Harrity T,Egan D,Morgan N,Cap M,Fura A,Klei HE,Kish K,Weigelt C,Sun L,Levesque P,Li YX,Zahler R,Kirby MS,Hamann LG

    更新日期:2011-11-15 00:00:00

  • Discovery and optimization of novel constrained pyrrolopyridone BET family inhibitors.

    abstract::Novel conformationally constrained BET bromodomain inhibitors have been developed. These inhibitors were optimized in two similar, yet distinct chemical series, the 6-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (A) and the 1-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (B). Each series demonstrated excellent activity in ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Fidanze SD,Liu D,Mantei RA,Hasvold LA,Pratt JK,Sheppard GS,Wang L,Holms JH,Dai Y,Aguirre A,Bogdan A,Dietrich JD,Marjanovic J,Park CH,Hutchins CW,Lin X,Bui MH,Huang X,Wilcox D,Li L,Wang R,Kovar P,Magoc TJ,Raj

    更新日期:2018-06-01 00:00:00

  • The design, synthesis and structure-activity relationships associated with C28 amine-based betulinic acid derivatives as inhibitors of HIV-1 maturation.

    abstract::The design and synthesis of a series of C28 amine-based betulinic acid derivatives as HIV-1 maturation inhibitors is described. This series represents a continuation of efforts following on from previous studies of C-3 benzoic acid-substituted betulinic acid derivatives as HIV-1 maturation inhibitors (MIs) that were e...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Chen Y,Sit SY,Chen J,Swidorski JJ,Liu Z,Sin N,Venables BL,Parker DD,Nowicka-Sans B,Lin Z,Li Z,Terry BJ,Protack T,Rahematpura S,Hanumegowda U,Jenkins S,Krystal M,Dicker ID,Meanwell NA,Regueiro-Ren A

    更新日期:2018-05-15 00:00:00

  • Enhanced radical scavenging activity of a procyanidin B3 analogue comprised of a dimer of planar catechin.

    abstract::Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and development of arteriosclerosis. Previous attempts aimed at developing proanthocya...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Mizuno M,Nakanishi I,Matsumoto KI,Fukuhara K

    更新日期:2017-11-15 00:00:00

  • Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2.

    abstract::This manuscript concludes the Structure Activity Relationship (SAR) on the pyridazinone scaffold and identifies a compound with subnanomolar p38α activity and 24h coverage in the rat arthritis efficacy model. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Tynebor RM,Chen MH,Natarajan SR,O'Neill EA,Thompson JE,Fitzgerald CE,O'Keefe SJ,Doherty JB

    更新日期:2012-09-15 00:00:00