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














  • Synthesis of novel bivalent mimetic ligands for mannose-6-phosphate receptors.

    abstract::Mannose-6-phosphate (M6P)-containing N-linked glycans are essential signaling molecules for sorting hydrolases in eukaryotic cells. Their receptors, especially the cation-independent M6P receptors (CI-MPRs), have emerged as promising protein targets for targeted drug delivery for the treatment of lysosomal storage dis...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Liu Y,Marshall J,Li Q,Edwards N,Chen G

    更新日期:2013-04-15 00:00:00

  • Synthesis of novel amide functionalized 2H-chromene derivatives by Ritter amidation of primary alcohol using HBF4·OEt2 as a mild and versatile reagent and evaluation of their antimicrobial and anti-biofilm activities.

    abstract::A series of novel amide functionalized 2H-chromene derivatives 3 were prepared starting from ethyl-2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate 1 via sodium borohydride reduction followed by Ritter amidation using HBF4·OEt2 as a mild and versatile reagent. All the products 3 were screened for antimicrobial ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ratnakar Reddy K,Poornachandra Y,Jitender Dev G,Mallareddy G,Nanubolu JB,Kumar CG,Narsaiah B

    更新日期:2015-08-01 00:00:00

  • Diamine preparation for synthesis of a water soluble Ni(II) salen complex.

    abstract::A reliable and efficient synthesis of a Ni(II) salen complex useful in probing nucleic acid structure is described and illustrates a general approach for constructing cis diamines suitable for assembly into N2O2 Schiff base complexes. Two equivalents of an aryllithium reacted with 1,4-dimethylpiperazine-2,3-dione to f...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Shearer JM,Rokita SE

    更新日期:1999-02-08 00:00:00

  • Investigation of the inhibitory mechanism of apomorphine against MDM2-p53 interaction.

    abstract::Mirror-image screening using d-proteins is a powerful approach to provide mirror-image structures of chiral natural products for drug screening. During the course of our screening study for novel MDM2-p53 interaction inhibitors, we identified that NPD6878 (R-(-)-apomorphine) inhibited both the native l-MDM2-l-p53 inte...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ishiba H,Noguchi T,Shu K,Ohno H,Honda K,Kondoh Y,Osada H,Fujii N,Oishi S

    更新日期:2017-06-01 00:00:00

  • Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

    abstract::New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were in...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Asano R,Nagami A,Fukumoto Y,Miura K,Yazama F,Ito H,Sakata I,Tai A

    更新日期:2014-03-01 00:00:00

  • Ejection of structural zinc leads to inhibition of γ-butyrobetaine hydroxylase.

    abstract::γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II) dependent oxygenase that catalyses an essential step during carnitine biosynthesis in animals. BBOX is inhibited by ejection of structural zinc by a set of selenium containing analogues. Previous structural analyses indicated that an undisrupted N-termi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Rydzik AM,Brem J,Struwe WB,Kochan GT,Benesch JL,Schofield CJ

    更新日期:2014-11-01 00:00:00

  • Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors.

    abstract::Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crys...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Huang X,Cheng CC,Fischmann TO,Duca JS,Richards M,Tadikonda PK,Reddy PA,Zhao L,Siddiqui MA,Parry D,Davis N,Seghezzi W,Wiswell D,Shipps GW Jr

    更新日期:2013-05-01 00:00:00

  • Synthesis, biological evaluation of 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone, 5-carboethoxymethyl-4',7-dihydroxyflavone and their analogues.

    abstract::In this letter, we describe the first synthesis of two recently isolated flavones 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone (3a), 5-carboethoxymethyl-4',7-dihydroxyflavone (3b) and their derivatives (3c-t), evaluated for their antimicrobial, antioxidant and anticancer activities. Most of the synthesized compound...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kamal A,Murty JN,Viswanath A,Sujitha P,Ganesh Kumar C

    更新日期:2012-07-15 00:00:00

  • Aminocyclohexylsulfonamides: discovery of metabolically stable alpha(1a/1d)-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS).

    abstract::Benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) can be effectively treated by alpha(1) adrenergic receptor antagonists, but these drugs also produce side effects that are related to their subtype non-selective nature. To overcome this limitation, it was hypothesized that an alpha(1a/1d) subtype-se...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Chiu G,Li S,Cai H,Connolly PJ,Peng S,Stauber K,Pulito V,Liu J,Middleton SA

    更新日期:2007-11-15 00:00:00

  • Synthesis of 2'-O-(N-methylcarbamoylethyl) 5-methyl-2-thiouridine and its application to splice-switching oligonucleotides.

    abstract::The effect of 2'-O-(N-methylcarbamoyl)ethyl (MCE) modification on splice-switching oligonucleotides (SSO) was systematically evaluated. The incorporation of five MCE nucleotides at the 5'-termini of SSOs effectively improved the splice switching effect. In addition, the incorporation of 2'-O-(N-methylcarbamoylethyl)-5...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Masaki Y,Yamamoto K,Inde T,Yoshida K,Maruyama A,Nagata T,Tanihata J,Takeda S,Sekine M,Seio K

    更新日期:2019-01-15 00:00:00

  • Novel endoperoxides: synthesis and activity against Candida species.

    abstract::Fifteen new endoperoxides have been synthesised and tested for activity against pathogenic Candida species. These endoperoxides can be prepared in high yields, in one to three steps, from inexpensive starting materials. Despite chemical and structural similarities, their inhibitory activity against Candida growth vari...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Macreadie P,Avery T,Greatrex B,Taylor D,Macreadie I

    更新日期:2006-02-15 00:00:00

  • Synthesis of stavudine amino acid ester prodrugs with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS.

    abstract::A series of prodrugs of stavudine were synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS. The 5'-OH function of stavudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide, piperazine and dimethylamine acetic acid. The anti-HIV-1 ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sriram D,Yogeeswari P,Srichakravarthy N,Bal TR

    更新日期:2004-03-08 00:00:00

  • Design and synthesis of novel substituted quinazoline derivatives as antileishmanial agents.

    abstract::4-(Substituted-benzylidine)-2-substituted-5,6-dihydrobenzo[h]quinazoline (5a-p) and 4-(substituted-benzylidine)-2-substituted-3, 4, 5, 6-tetrahydrobenzo[h]quinazoline (6a-p) have been synthesized from 2-(substituted-benzylidine)tetralone-1(3a-d) and several substituted guanidine sulfates(4a-d).These compounds were tes...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Agarwal KC,Sharma V,Shakya N,Gupta S

    更新日期:2009-09-15 00:00:00

  • A practical deuterium-free NMR method for the rapid determination of 1-octanol/water partition coefficients of pharmaceutical agents.

    abstract::A simple and rapid NMR method is described to determine the logP of pharmaceutical agents. This method is highly versatile and efficient, because it does not require the use of deuterated solvents or the addition of any internal/external standards to the sample. We demonstrate that logP can be accurately measured usin...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Mo H,Balko KM,Colby DA

    更新日期:2010-11-15 00:00:00

  • Synthesis and cytotoxic evaluation of novel ester-triazole-linked triterpenoid-AZT conjugates.

    abstract::Betulinic acid and analogous naturally occurring triterpenoid acids were transformed into the corresponding propargyl esters and subsequently deployed as substrates for a click chemistry-mediated coupling with azidothymidine (AZT) en route to novel 1,2,3-triazole-tethered triterpenoid-AZT conjugates. Twelve new hybrid...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dang Thi TA,Kim Tuyet NT,Pham The C,Thanh Nguyen H,Ba Thi C,Doan Duy T,D'hooghe M,Van Nguyen T

    更新日期:2014-11-15 00:00:00

  • Epicubenol synthase. Origin of the oxygen atom of a bacterial sesquiterpene alcohol.

    abstract::Incubation of epicubenol synthase with farnesyl pyrophosphate in the presence of 11.1 atom% H2(18)O gave epicubenol (2) in which the hydroxyl oxygen atom was shown to be derived exclusively from water, as established by GC-selected ion monitoring MS of the derived TMS-epicubenol derivative (15). ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Cane DE,Ke N

    更新日期:2000-01-17 00:00:00

  • Studies on the novel anti-staphyloccal compound nematophin.

    abstract::A number of analogues of the recently described compound nematophin were prepared and studied for antibacterial activity. The 2-phenyl derivative was found to exhibit exceptional activity against methicillin resistant Staphylococcus aureus (MRSA) whereas the isosteric benzimidazole analogue was much less active. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kennedy G,Viziano M,Winders JA,Cavallini P,Gevi M,Micheli F,Rodegher P,Seneci P,Zumerle A

    更新日期:2000-08-07 00:00:00

  • Structural hybridization as a facile approach to new drug candidates.

    abstract::Structural hybridization of preclinically and clinically validated pharmacologically active molecules has emerged as a promising tool to develop new generations of safe and highly efficient drug candidates against various diseases including microbial infections, virus infections and cancer. Strategies of drug-drug com...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章,评审


    authors: Sampath Kumar HM,Herrmann L,Tsogoeva SB

    更新日期:2020-12-01 00:00:00

  • Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing.

    abstract::The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Li Z,Powell CE,Groendyke BJ,Gero TW,Feru F,Feutrill J,Chen B,Li B,Szabo H,Gray NS,Scott DA

    更新日期:2020-10-01 00:00:00

  • Preparation of novel anthranilic acids as antibacterial agents: extensive evaluation of structural and physical properties on antibacterial activity and human serum albumin affinity.

    abstract::In the past few years a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected analogs ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Thorarensen A,Li J,Wakefield BD,Romero DL,Marotti KR,Sweeney MT,Zurenko GE,Sarver RW

    更新日期:2007-06-01 00:00:00

  • Synthesis of potent taxoids for tumor-specific delivery using monoclonal antibodies.

    abstract::The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prep...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Miller ML,Roller EE,Wu X,Leece BA,Goldmacher VS,Chari RV,Ojima I

    更新日期:2004-08-02 00:00:00

  • N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1-XPF.

    abstract::A high throughput screen allowed the identification of N-hydroxyimide inhibitors of ERCC1-XPF endonuclease activity with micromolar potency, but they showed undesirable selectivity profiles against FEN-1. A scaffold hop to a hydroxypyrimidinone template gave compounds with similar potency but allowed selectivity to be...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Chapman TM,Wallace C,Gillen KJ,Bakrania P,Khurana P,Coombs PJ,Fox S,Bureau EA,Brownlees J,Melton DW,Saxty B

    更新日期:2015-10-01 00:00:00

  • Regio-reactive resin: a platform for orthogonal loading using the polymer backbone and cross-linker.

    abstract::A new support for solid-phase combinatorial organic synthesis has been developed, which we term a regio-reactive resin (R(3)-resin). The resin is based on a unique hydroxyl-functionalized cross-linker readily synthesized in two steps starting from 4-hydroxybenzaldehyde. The cross-linker's ease of synthesis and high pu...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dickerson TJ,Reed NN,Janda KD

    更新日期:2001-06-18 00:00:00

  • [11C]GSK2126458 and [18F]GSK2126458, the first radiosynthesis of new potential PET agents for imaging of PI3K and mTOR in cancers.

    abstract::GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [(11)C]GSK2126458 and [(18)F]GSK2126458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 2...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wang M,Gao M,Miller KD,Sledge GW,Zheng QH

    更新日期:2012-02-15 00:00:00

  • Synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors.

    abstract::A series of N1-activated C4-carboxy azetidinones was prepared and tested as inhibitors of human tryptase. The key stereochemical and functional features required for potency, serine protease specificity and aqueous stability were determined. From these studies compound 2, BMS-262084, was identified as a potent and sel...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sutton JC,Bolton SA,Hartl KS,Huang MH,Jacobs G,Meng W,Ogletree ML,Pi Z,Schumacher WA,Seiler SM,Slusarchyk WA,Treuner U,Zahler R,Zhao G,Bisacchi GS

    更新日期:2002-11-04 00:00:00

  • Identification and optimization of novel 1,3,4-oxadiazole EP1 receptor antagonists.

    abstract::A novel series of oxadiazole EP1 receptor antagonists was identified by replacing the amide of a known glycine sulfonamide derivative with a 1,3,4-oxadiazole. Optimization of the substitution patterns on the three aromatic rings led to the identification of high affinity EP1 receptor antagonists. The derivative with h...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hall A,Brown SH,Chowdhury A,Giblin GM,Gibson M,Healy MP,Livermore DG,Wilson RJ,Naylor A,Rawlings DA,Roman S,Ward E,Willay C

    更新日期:2007-08-15 00:00:00

  • Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354.

    abstract::Herein we report the discovery and SAR of an indole-based protease activated receptor-4 (PAR-4) antagonist scaffold derived from a similarity search of the Vanderbilt HTS collection, leading to MLPCN probe ML354 (VU0099704). Using a novel PAC-1 fluorescent αIIbβ3 activation assay this probe molecule antagonist was fou...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wen W,Young SE,Duvernay MT,Schulte ML,Nance KD,Melancon BJ,Engers J,Locuson CW 2nd,Wood MR,Daniels JS,Wu W,Lindsley CW,Hamm HE,Stauffer SR

    更新日期:2014-10-01 00:00:00

  • Triptolide derivatives as potential multifunctional anti-Alzheimer agents: Synthesis and structure-activity relationship studies.

    abstract::Owning to the promising neuroprotective profile and the ability to cross the blood-brain barrier, triptolide has attracted extensive attention. Although its limited solubility and toxicity have greatly hindered clinical translation, triptolide has nonetheless emerged as a promising candidate for structure-activity rel...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ning C,Mo L,Chen X,Tu W,Wu J,Hou S,Xu J

    更新日期:2018-02-15 00:00:00

  • New coumarin-benzotriazole based hybrid molecules as inhibitors of acetylcholinesterase and amyloid aggregation.

    abstract::A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 μΜ) with ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Singh A,Sharma S,Arora S,Attri S,Kaur P,Kaur Gulati H,Bhagat K,Kumar N,Singh H,Vir Singh J,Mohinder Singh Bedi P

    更新日期:2020-10-15 00:00:00

  • 2,5-Diketopiperazines as potent and selective oxytocin antagonists 1: Identification, stereochemistry and initial SAR.

    abstract::This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the d...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wyatt PG,Allen MJ,Borthwick AD,Davies DE,Exall AM,Hatley RJ,Irving WR,Livermore DG,Miller ND,Nerozzi F,Sollis SL,Szardenings AK

    更新日期:2005-05-16 00:00:00