当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Camptothecin analogs with bulky, hydrophobic substituents at the 7-position via a Grignard reaction.

Camptothecin analogs with bulky, hydrophobic substituents at the 7-position via a Grignard reaction.

Abstract：

:By developing a new synthetic procedure for introduction of side chains onto the camptothecin ring system, we were able to achieve the preparation of a number of analogs bearing bulky, hydrophobic groups directly attached to the 7-position. These include 7-tert-butylcamptothecin, 7-benzylcamptothecin and the corresponding 10,11-methylenedioxycamptothecins. This method involves the reaction of an appropriate orthoaminobenzonitrile with various Grignard reagents to give the corresponding orthoaminoketones. Friedlander condensation of the latter with the key tricyclic ketone leads to 7-substituted camptothecin analogs. We report the activity of these compounds as topoisomerase I poisons and their ability to inhibit growth of selected tumor cell lines.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Manikumar G,Wadkins RM,Bearss D,Von Hoff DD,Wani MC,Wall ME

doi

10.1016/j.bmcl.2004.08.010

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

5377-81

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(04)01018-2

journal_volume

14

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Discovery of triazolo [1,5-a] pyridine derivatives as novel JAK1/2 inhibitors.

    abstract：:Small molecule JAK inhibitors have been demonstrated efficacy in rheumatoid arthritis, inflammatory bowel disease, and psoriasis with the approval of several drugs. Aiming to develop potent JAK1/2 inhibitors, two series of triazolo [1,5-a] pyridine derivatives were designed and synthesized by various strategies. The p...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127225

    authors： Lu K,Wu W,Zhang C,Liu Z,Xiao B,Yuan Z,Li A,Chen D,Zhai X,Jiang Y

    更新日期：2020-07-15 00:00:00

  • Discovery of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides as small molecule inhibitors of PCSK9.

    abstract：:A series of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides were identified as small molecule PCSK9 mRNA translation inhibitors. Analogues from this new chemical series, such as 4d and 4g, exhibited improved PCSK9 potency, ADME properties, and in vitro safety profiles when compared to earlier l...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.10.029

    authors： Londregan AT,Aspnes G,Limberakis C,Loria PM,McClure KF,Petersen DN,Raymer B,Ruggeri RB,Wei L,Xiao J,Piotrowski DW

    更新日期：2018-12-15 00:00:00

  • 3-(Cyclopropylmethyl)-7-((4-(4-[11C]methoxyphenyl)piperidin-1-yl)methyl)-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine: Synthesis and preliminary evaluation for PET imaging of metabotropic glutamate receptor subtype 2.

    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

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127555

    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

  • 4-Aryl-2-anilinopyrimidines as corticotropin-releasing hormone (CRH) antagonists.

    abstract：:A series of 4-aryl-2-(N-ethylanilino)pyrimidines has been synthesized as corticotropin-releasing hormone (CRH) inhibitors. The effect of substitution on each aromatic ring on receptor binding was investigated. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00132-8

    authors： Cocuzza AJ,Hobbs FW,Arnold CR,Chidester DR,Yarem JA,Culp S,Fitzgerald L,Gilligan PJ

    更新日期：1999-04-05 00:00:00

  • Two new secondary metabolites isolated from Avena sativa L. (Oat) seedlings and their effects on osteoblast differentiation.

    abstract：:Seedlings of natural crops are valuable sources of pharmacologically active phytochemicals. In this study, we aimed to identify new active secondary metabolites in Avena sativa L. (oat) seedlings. Two new compounds, avenafuranol (1) and diosgenoside (2), along with eight known compounds (3-10) were isolated from the A...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127250

    authors： Woo SY,Lee KS,Shin HL,Kim SH,Lee MJ,Young Kim H,Ham H,Lee DJ,Choi SW,Seo WD

    更新日期：2020-07-15 00:00:00

  • Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors.

    abstract：:A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC(50) values in the range of 10-150 nM and selectivity over the L-type channels up to nearly...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.01.008

    authors： Pajouhesh H,Feng ZP,Ding Y,Zhang L,Pajouhesh H,Morrison JL,Belardetti F,Tringham E,Simonson E,Vanderah TW,Porreca F,Zamponi GW,Mitscher LA,Snutch TP

    更新日期：2010-02-15 00:00:00

  • Synthesis and biological evaluation of a new class of vaccine adjuvants: aminoalkyl glucosaminide 4-phosphates (AGPs).

    abstract：:A novel series of acylated omega-aminoalkyl 2-amino-2-deoxy-4-phosphono-beta-D-glucopyranosides (aminoalkyl glucosaminide 4-phosphates) was synthesized and screened for immunostimulant activity. Several of these compounds enhance the production of tetanus toxoid-specific antibodies in mice and augment vaccine-induced ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00374-1

    authors： Johnson DA,Sowell CG,Johnson CL,Livesay MT,Keegan DS,Rhodes MJ,Ulrich JT,Ward JR,Cantrell JL,Brookshire VG

    更新日期：1999-08-02 00:00:00

  • Identification and characterization of β-sitosterol target proteins.

    abstract：:β-Sitosterol is the most abundant plant sterol in the human diet. It is also the major component of several traditional medicines, including saw palmetto and devil's claw. Although β-sitosterol is effective against enlarged prostate in human clinical trials and has anti-cancer and anti-inflammatory activities, the mec...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.03.007

    authors： Lomenick B,Shi H,Huang J,Chen C

    更新日期：2015-11-01 00:00:00

  • Cyclin dependent kinase (CDK) inhibitors as anticancer drugs: Recent advances (2015-2019).

    abstract：:Sustained proliferative capacity and gene dysregulation are hallmarks of cancer. In mammalian cells, cyclin-dependent kinases (CDKs) control critical cell cycle checkpoints and key transcriptional events in response to extracellular and intracellular signals leading to proliferation. Significant clinical activity for ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2019.126637

    authors： Sánchez-Martínez C,Lallena MJ,Sanfeliciano SG,de Dios A

    更新日期：2019-10-15 00:00:00

  • Novel naftopidil derivatives containing methyl phenylacetate and their blocking effects on α1D/1A-adrenoreceptor subtypes.

    abstract：:α1-Adrenoceptor (α1-AR) antagonists are considered to be the most effective monotherapy agents for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). In this study, we synthesized compounds 2-17, which are novel piperazine derivatives that contain methyl phenylacetate. We then evalua...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.01.068

    authors： Huang JJ,Zhang ZH,He F,Liu XW,Xu XJ,Dai LJ,Liu QM,Yuan M

    更新日期：2018-02-15 00:00:00

  • Dihydrodibenzothiepine: Promising hydrophobic pharmacophore in the influenza cap-dependent endonuclease inhibitor.

    abstract：:This work describes a set of discovery research studies of an influenza cap-dependent endonuclease (CEN) inhibitor with a carbamoyl pyridone bicycle (CAB) scaffold. Using influenza CEN inhibitory activity, antiviral activity and pharmacokinetic (PK) parameters as indices, structure activity relationships (SAR) studies...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127547

    authors： Taoda Y,Miyagawa M,Akiyama T,Tomita K,Hasegawa Y,Yoshida R,Noshi T,Shishido T,Kawai M

    更新日期：2020-11-15 00:00:00

  • A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 to identify new inhibitors of gp120-CD4 protein-protein interactions.

    abstract：:A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 was built and used to identify new hits able to inhibit gp120-CD4 protein-protein interactions. Two compounds showed micromolar inhibition of HIV-1 replication in cells attributable to an interference with the entry step of infecti...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.029

    authors： Caporuscio F,Tafi A,González E,Manetti F,Esté JA,Botta M

    更新日期：2009-11-01 00:00:00

  • Novel derivatives of 3-(dipropylamino)chroman. Interactions with 5-HT1A and D2A receptors.

    abstract：:Novel 8-aryl and 8-aroyl substituted derivatives of 3-(dipropylamino)chroman are described. The compounds have been prepared by a palladium catalyzed reaction of iodoarenes and a stannylated derivative of [eta6-3-(dipropylamino)chroman]Cr(CO)3. Several of the compounds have high affinity for 5-HT1A receptors whereas t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00232-2

    authors： Caldirola P,Chowdhury R,Unelius L,Mohell N,Hacksell U,Johansson AM

    更新日期：1999-06-07 00:00:00

  • Discovery of LRRK2 inhibitors by using an ensemble of virtual screening methods.

    abstract：:In this paper, we present the results of a ligand- and structure-based virtual screen targeting LRRK2, a kinase that has been implicated in Parkinson's disease. For the ligand-based virtual screen, the structures of 12 competitor compounds were used as queries for a variety of 2D and 3D searches. The structure-based v...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.03.098

    authors： Gancia E,De Groot M,Burton B,Clark DE

    更新日期：2017-06-01 00:00:00

  • Protection of a single-cysteine redox switch from oxidative destruction: On the functional role of sulfenyl amide formation in the redox-regulated enzyme PTP1B.

    abstract：:Model reactions offer a chemical mechanism by which formation of a sulfenyl amide residue at the active site of the redox-regulated protein tyrosine phosphatase PTP1B protects the cysteine redox switch in this enzyme against irreversible oxidative destruction. The results suggest that 'overoxidation' of the sulfenyl a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.12.001

    authors： Sivaramakrishnan S,Cummings AH,Gates KS

    更新日期：2010-01-15 00:00:00

  • New antiprotozoal agents: their synthesis and biological evaluations.

    abstract：:Here we report identification of new lead compounds based on quinoline and indenoquinolines with variable side chains as antiprotozoal agents. Quinolines 32, 36 and 37 (Table 1) and indenoquinoline derivatives 14 and 23 (Table 2) inhibit the in vitro growth of the Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma bru...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.054

    authors： Upadhayaya RS,Dixit SS,Földesi A,Chattopadhyaya J

    更新日期：2013-05-01 00:00:00

  • Aminofurazans as potent inhibitors of AKT kinase.

    abstract：:AKT inhibitors containing an imidazopyridine aminofurazan scaffold have been optimized. We have previously disclosed identification of the AKT inhibitor GSK690693, which has been evaluated in clinical trials in cancer patients. Herein we describe recent efforts focusing on investigating a distinct region of this scaff...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.01.002

    authors： Rouse MB,Seefeld MA,Leber JD,McNulty KC,Sun L,Miller WH,Zhang S,Minthorn EA,Concha NO,Choudhry AE,Schaber MD,Heerding DA

    更新日期：2009-03-01 00:00:00

  • Selective cytochrome P450 3A4 inhibitory activity of Amaryllidaceae alkaloids.

    abstract：:A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.04.086

    authors： McNulty J,Nair JJ,Singh M,Crankshaw DJ,Holloway AC,Bastida J

    更新日期：2009-06-15 00:00:00

  • Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs) inspired by filorexant.

    abstract：:Highly selective orexin receptor antagonists (SORAs) of the orexin 2 receptor (OX2R) have become attractive targets both as potential therapeutics for insomnia as well as biological tools to help further elucidate the underlying pharmacology of the orexin signaling pathway. Herein, we describe the discovery of a novel...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.12.056

    authors： Raheem IT,Breslin MJ,Bruno J,Cabalu TD,Cooke A,Cox CD,Cui D,Garson S,Gotter AL,Fox SV,Harrell CM,Kuduk SD,Lemaire W,Prueksaritanont T,Renger JJ,Stump C,Tannenbaum PL,Williams PD,Winrow CJ,Coleman PJ

    更新日期：2015-02-01 00:00:00

  • Enediynyl peptides and iso-coumarinyl methyl sulfones as inhibitors of proprotein convertases PCSK8/SKI-1/S1P and PCSK4/PC4: Design, synthesis and biological evaluations.

    abstract：:The proprotein convertases PCSK8 and PCSK4 are, respectively, the 8th and 4th members of Ca(+2)-dependent serine endoprotease of Proprotein Convertase Subtilisin Kexin (PCSK) super family structurally related to the bacterial subtilisin and yeast kexin. The membrane bound PCSK8 (also called SKI-1 or S1P) is implicated...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.03.029

    authors： Basak A,Goswami M,Rajkumar A,Mitra T,Majumdar S,O'Reilly P,Bdour HM,Trudeau VL,Basak A

    更新日期：2015-01-01 00:00:00

  • Conformational study of a highly specific CXCR4 inhibitor, T140, disclosing the close proximity of its intrinsic pharmacophores associated with strong anti-HIV activity.

    abstract：:We report the solution structure of T140, a truncated polyphemusin peptide analogue that efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 through its specific binding to a chemokine receptor, CXCR4. Nuclear magnetic resonance analysis and molecular dynamic calculations revealed tha...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00664-8

    authors： Tamamura H,Sugioka M,Odagaki Y,Omagari A,Kan Y,Oishi S,Nakashima H,Yamamoto N,Peiper SC,Hamanaka N,Otaka A,Fujii N

    更新日期：2001-02-12 00:00:00

  • Oxyguanidines: application to non-peptidic phenyl-based thrombin inhibitors.

    abstract：:Although thrombin has been extensively researched with many examples of potent and selective inhibitors, the key characteristics of oral bioavailability and long half-life have been elusive. We report here a novel series non-peptidic phenyl-based, highly potent, highly selective and orally bioavailable thrombin inhibi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00125-2

    authors： Tomczuk B,Lu T,Soll RM,Fedde C,Wang A,Murphy L,Crysler C,Dasgupta M,Eisennagel S,Spurlino J,Bone R

    更新日期：2003-04-17 00:00:00

  • Novel antibacterial active quinolone-fluoroquinolone conjugates and 2D-QSAR studies.

    abstract：:Novel, quinolone-fluoroquinolone conjugates 10a-f, 11a-f, 13a-f and 14a-f with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antibacterial bioassay showed the synthesized bis-conjugates exhibit anti-bacterial properties comparable with the parent drugs. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.07.077

    authors： Panda SS,Liaqat S,Girgis AS,Samir A,Hall CD,Katritzky AR

    更新日期：2015-09-15 00:00:00

  • Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines. Part 2.

    abstract：:A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives 8g, ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.05.004

    authors： Jung MH,El-Gamal MI,Abdel-Maksoud MS,Sim T,Yoo KH,Oh CH

    更新日期：2012-07-01 00:00:00

  • Synthesis of rare sugars with L-fuculose-1-phosphate aldolase (FucA) from Thermus thermophilus HB8.

    abstract：:We report herein a one-pot four-enzyme approach for the synthesis of the rare sugars d-psicose, d-sorbose, l-tagatose, and l-fructose with aldolase FucA from a thermophilic source (Thermus thermophilus HB8). Importantly, the cheap starting material DL-GP (DL-glycerol 3-phosphate), was used to significantly reduce the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.03.072

    authors： Li Z,Cai L,Qi Q,Styslinger TJ,Zhao G,Wang PG

    更新日期：2011-09-01 00:00:00

  • Substituted sulfonamide bioisosteres of 8-hydroxyquinoline as zinc-dependent antibacterial compounds.

    abstract：:A series of substituted sulfonamide bioisosteres of 8-hydroxyquinoline were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc. Compounds 9a-e, 10a-c, 11a-e, ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127110

    authors： McGowan JE,Harper AD,Davison EK,Jeong JY,Mros S,Harbison-Price N,Van Zuylen EM,Knottenbelt MK,Heikal A,Ferguson SA,McConnell MA,Cook GM,Krittaphol W,Walker GF,Brimble MA,Rennison D

    更新日期：2020-06-01 00:00:00

  • Juglone, isolated from Juglans mandshurica Maxim, induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells.

    abstract：:Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim. Recent studies have shown that juglone had various pharmacological effects such as anti-viral, anti-bacterial and anti-cancer. However, its anti-cancer activity on human prostate cancer LNCaP cell has not been examined. Thus, the cur...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 信件

    doi：10.1016/j.bmcl.2013.04.007

    authors： Xu H,Yu X,Qu S,Sui D

    更新日期：2013-06-15 00:00:00

  • Inhibition of HIV-1 infection by synthetic peptide analogues derived from the NH(2)-Terminal extracellular region of GPR1.

    abstract：:Several shortened peptide analogues of the N-terminal domain of GPR1, an orphan G protein-coupled receptor (GPCR), were prepared and their anti-HIV-1 activities were evaluated. Some of the prepared compounds, especially sulfated derivatives, showed potent inhibitory activity against a broad range of HIV-1, including T...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00503-0

    authors： Ikeda K,Konishi K,Sato M,Hoshino H,Tanaka K

    更新日期：2001-10-08 00:00:00

  • Use of parallel-synthesis combinatorial libraries for rapid identification of potent FKBP12 inhibitors.

    abstract：:Using simple, inexpensive equipment, we have used solution-phase parallel synthesis to rapidly prepare hundreds of sulfonamide- and urea-containing FKBP inhibitors, resulting in rapid identification of extremely potent compounds in these series. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00147-6

    authors： Choi C,Li JH,Vaal M,Thomas C,Limburg D,Wu YQ,Chen Y,Soni R,Scott C,Ross DT,Guo H,Howorth P,Valentine H,Liang S,Spicer D,Fuller M,Steiner J,Hamilton GS

    更新日期：2002-05-20 00:00:00

  • Flavonoids from Woodfordia fruticosa as potential SmltD inhibitors in the alternative biosynthetic pathway of peptidoglycan.

    abstract：:SmltD is an ATP-dependent ligase that catalyzes the condensation of UDP-MurNAc-l-Ala and l-Glu to form UDP-MurNAc-l-Ala-l-Glu, in the newly discovered peptidoglycan biosynthesis pathway of a Gram-negative multiple-drug-resistant pathogen, Stenotrophomonas maltophilia. Phytochemical investigation of the 70% ethanol ext...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2021.127787

    authors： Lee YE,Kodama T,Win NN,Ki DW,Hoang NN,Wong CP,Lae KZW,Ngwe H,Dairi T,Morita H

    更新日期：2021-01-15 00:00:00