当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti-HIV agents.

Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti-HIV agents.

Abstract：

:Novel polyhalo 2,4-diaminoquinazolines 3a-3d were prepared by reacting polyhaloisophthalonitriles with guanidine carbonate under solvent-free conditions and in the absence of a catalyst with good yields (74-95%). A series of highly functionalized 2,4-diaminoquinazolines 4-5 were then synthesized based on 3a-3c. The anticancer activities of compounds 3-5 were evaluated in vitro against human cell lines such as Skov-3, HL-60, A431, A549, and HepG-2. Some of the compounds showed excellent cytotoxic activity and 5a was found to be the most potent derivative, with an IC(50) value lower than 2.5 microg/mL against the five tumor cell lines, making it more active than cisplatin. Representative compounds were also preliminarily evaluated as HIV-1 inhibitors in vitro, and 3c showed the most potent anti-HIV-1 activity with EC(50) values of 0.6 and 1.6 microg/mL, and TI values of >59.6 and 66.6, respectively.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Yan SJ,Zheng H,Huang C,Yan YY,Lin J

doi

10.1016/j.bmcl.2010.06.056

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

4432-5

issue

15

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)00830-9

journal_volume

20

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • The design of phenylglycine containing benzamidine carboxamides as potent and selective inhibitors of factor Xa.

    abstract：:Factor Xa, a critical serine protease in the blood coagulation cascade, has become a target for inhibition as a strategy for the invention of novel anti-thrombotic agents. Here we describe the development of phenylglycine containing benzamidine carboxamides as novel, potent and selective inhibitors of factor Xa. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00042-7

    authors： Jones SD,Liebeschuetz JW,Morgan PJ,Murray CW,Rimmer AD,Roscoe JM,Waszkowycz B,Welsh PM,Wylie WA,Young SC,Martin H,Mahler J,Brady L,Wilkinson K

    更新日期：2001-03-12 00:00:00

  • Discovery of mu-opioid selective ligands derived from 1-aminotetralin scaffolds made via metal-catalyzed ring-opening reactions.

    abstract：:A series of 1-aminotetralin scaffolds was synthesized via metal-catalyzed ring-opening reactions of heterobicyclic alkenes. Small libraries of amides and amines were made using the amino group of each scaffold as a handle. Screening of these libraries against human opioid receptors led to the identification of (S)-(S)...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.12.095

    authors： Dockendorff C,Jin S,Olsen M,Lautens M,Coupal M,Hodzic L,Spear N,Payza K,Walpole C,Tomaszewski MJ

    更新日期：2009-02-15 00:00:00

  • An amide-based sulfenamide prodrug of gamma secretase inhibitor BMS-708163 delivers parent drug from an oral conventional solid dosage form in male beagle dog.

    abstract：:The objective of this Letter is to report the first (to our knowledge) in vivo proof of concept for a sulfenamide prodrug to orally deliver a poorly soluble drug containing a weakly-acidic NH-acid from a conventional solid dosage formulation. This proof of concept was established using BMS-708163 (1), a gamma secretas...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.126856

    authors： Guarino VR,Olson RE,Everlof JG,Wang N,McDonald I,Haskell R,Clarke W,Lentz KA

    更新日期：2020-02-01 00:00:00

  • Design, synthesis and binding affinity of acetylcholine carbamoyl analogues.

    abstract：:A series of acetylcholine carbamoyl analogues, cyclised at the carbamate moiety or at the cationic head or at both, were tested for binding affinity at muscarinic and neuronal nicotinic receptors (nAChRs). While no muscarinic affinity was found, submicromolar Ki values, similar to that of carbachol, were measured at α...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.09.023

    authors： Bolchi C,Valoti E,Binda M,Fasoli F,Ferrara R,Fumagalli L,Gotti C,Matucci R,Vistoli G,Pallavicini M

    更新日期：2013-12-01 00:00:00

  • Colorectal anticancer activities of polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamides.

    abstract：:To develop potent chemotherapeutic agents for treating colorectal cancers, polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamide derivatives were designed. Twenty-two novel derivatives were synthesized and their cytotoxicities were measured using a clonogenic long-term survival assay. Of these derivatives, 3-(...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.07.037

    authors： Shin SY,Ahn S,Yoon H,Jung H,Jung Y,Koh D,Lee YH,Lim Y

    更新日期：2016-09-01 00:00:00

  • Discovery and biological activity of computer-assisted drug designed Akt pathway inhibitors.

    abstract：:The P13K/Akt pathway is a growth-regulating cellular signaling pathway that is over-activated in numerous human cancers. A novel series of Akt pathway inhibitors were identified using iterative pharmacophore modeling, energy-based calculations, and property predictions of known Akt inhibitors. Inhibitory effects on ac...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.08.006

    authors： Uko NE,Güner OF,Barnett LMA,Matesic DF,Bowen JP

    更新日期：2018-10-15 00:00:00

  • Synthesis and biological evaluation of piperamide analogues as HDAC inhibitors.

    abstract：:Two natural piperamides (piperlonguminine and refrofractamide A) and their derivatives were synthesized and evaluated for inhibitory activity against histone deacetylases, as well as the HCT-116 human colon cancer cell line. The preliminary structure activity relationship was discussed. Compounds featuring a hydroxami...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.06.046

    authors： Luo Y,Liu HM,Su MB,Sheng L,Zhou YB,Li J,Lu W

    更新日期：2011-08-15 00:00:00

  • Synthesis and biological activity of 4-substituted benzoxazolone derivatives as a new class of sEH inhibitors with high anti-inflammatory activity in vivo.

    abstract：:A series of novel 4-substituted benzoxazolone derivatives was synthesized, characterized and evaluated as human soluble epoxide hydrolase (sEH) inhibitors and anti-inflammatory agents. Some compounds showed moderate sEH inhibitory activities in vitro, and two novel compounds, 3g and 4j, exhibited the highest activitie...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.048

    authors： Tang L,Ma WH,Ma YL,Ban SR,Feng XE,Li QS

    更新日期：2013-04-15 00:00:00

  • Synthesis, structural properties and insulin-enhancing potential of bis(quercetinato)oxovanadium(IV) conjugate.

    abstract：:An oxovanadium complex of quercetin (2), exhibits highly potent insulin-enhancing activity in streptozotocin-induced diabetic mice. It also mimics mitogenic potential of insulin as evaluated by [H(3)]thymidine uptake assay making an effective, orally active insulin-enhancing agent for the treatment of both type 1 and ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.07.020

    authors： Shukla R,Barve V,Padhye S,Bhonde R

    更新日期：2004-10-04 00:00:00

  • Delta agonist hydroxy bioisosteres: the discovery of 3-((1-benzylpiperidin-4-yl){4-[(diethylamino)carbonyl]phenyl}amino)benzamide with improved delta agonist activity and in vitro metabolic stability.

    abstract：:We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.068

    authors： Griffin AM,Brown W,Walpole C,Coupal M,Adam L,Gosselin M,Salois D,Morin PE,Roumi M

    更新日期：2009-11-01 00:00:00

  • Pyrrolo[3,2,1-ij]quinoline derivatives, a 5-HT2c receptor agonist with selectivity over the 5-HT2a receptor: potential therapeutic applications for epilepsy and obesity.

    abstract：:A series of pyrrolo[3,2,1-ij]quinoline derivatives was synthesized, evaluated for their activity against the 5-HT2c and 5-HT2a, receptors and found to be agonists at 5-HT2c with selectivity over 5-HT2a. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00141-4

    authors： Isaac M,Slassi A,O'Brien A,Edwards L,MacLean N,Bueschkens D,Lee DK,McCallum K,De Lannoy I,Demchyshyn L,Kamboj R

    更新日期：2000-05-01 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

    doi：10.1016/j.bmcl.2018.01.019

    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

  • Synthesis of Keap1-phosphorylated p62 and Keap1-Nrf2 protein-protein interaction inhibitors and their inhibitory activity.

    abstract：:The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and surviva...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.10.083

    authors： Yasuda D,Nakajima M,Yuasa A,Obata R,Takahashi K,Ohe T,Ichimura Y,Komatsu M,Yamamoto M,Imamura R,Kojima H,Okabe T,Nagano T,Mashino T

    更新日期：2016-12-15 00:00:00

  • Zinc(II)-mediated inhibition of a ribonuclease by an N-hydroxyurea nucleotide.

    abstract：:The inhibition of ribonuclease Bi by 3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate is enhanced by 30-fold in the presence of Zn(2+). Thus, an N-hydroxyurea nucleotide can recruit Zn(2+) to inhibit the enzymatic activity of a ribonuclease. This result engenders a general strategy for the inhibition of non-metalloenzy...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00929-0

    authors： Higgin JJ,Yakovlev GI,Mitkevich VA,Makarov AA,Raines RT

    更新日期：2003-02-10 00:00:00

  • Using enzymatic amplification by aldolase for the optical detection of DNA by an artificial signal cascade.

    abstract：:A two-step reaction cascade is applied to the sequence-specific detection of single-stranded DNA, including analyte-triggered re-activation of apo-aldolase by its cofactor Zn(2+) and catalytic conversion of a chromophore. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.07.102

    authors： Graf N,Kassube S,Krämer R

    更新日期：2008-09-01 00:00:00

  • Chemical control of metabolically-engineered voltage-gated K+ channels.

    abstract：:Metabolic oligosaccharide engineering is a powerful approach for installing unnatural glycans with unique functional groups into the glycocalyx of living cells and animals. Using this approach, we showed that K(+) channel complexes decorated with thiol-containing sialic acids were irreversibly inhibited with scorpion ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.04.099

    authors： Hua Z,Lvov A,Morin TJ,Kobertz WR

    更新日期：2011-09-01 00:00:00

  • Reaction of naphthoquinones with substituted nitromethanes. Facile synthesis and antifungal activity of naphtho[2,3-d]isoxazole-4,9-diones.

    abstract：:We report here a simple entry into naphtho[2,3-d]isoxazole-4,9-dione system containing a EWG in position 3 using the readily available 2,3-dichloro-1,4-naphthoquinone and nitromethyl derivatives in the presence of base. Antifungal activity of synthesised naphthoquinones was evaluated against ATCC and PYCC reference st...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.10.137

    authors： Santos MM,Faria N,Iley J,Coles SJ,Hursthouse MB,Martins ML,Moreira R

    更新日期：2010-01-01 00:00:00

  • Prototyping kinase inhibitor-cytotoxin anticancer mutual prodrugs activated by tumour hypoxia: A chemical proof of concept study.

    abstract：:Amide- and ester-linked kinase inhibitor-cytotoxin conjugates were rationally designed and synthesised as prototype hypoxia-activated anticancer mutual prodrugs. Chemical reduction of an aryl nitro trigger moiety was shown to initiate a spontaneous cyclisation/fragmentation reaction that simultaneously released the ki...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.03.015

    authors： Sansom GN,Kirk NS,Guise CP,Anderson RF,Smaill JB,Patterson AV,Kelso MJ

    更新日期：2019-05-15 00:00:00

  • Synthesis and evaluation of cholecystokinin trimers: a multivalent approach to pancreatic cancer detection and treatment.

    abstract：:In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.022

    authors： Brabez N,Nguyen KL,Saunders K,Lacy R,Xu L,Gillies RJ,Lynch RM,Chassaing G,Lavielle S,Hruby VJ

    更新日期：2013-04-15 00:00:00

  • Carbonic anhydrase inhibitors. Inhibition of the zinc and cobalt gamma-class enzyme from the archaeon Methanosarcina thermophila with anions.

    abstract：:Anions represent the second class of inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), in addition to sulfonamides, which possess clinical applications. The first inhibition study of the zinc and cobalt gamma-class enzyme from the archaeon Methanosarcina thermophila (Cam) with anions is reported here....

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.03.101

    authors： Innocenti A,Zimmerman S,Ferry JG,Scozzafava A,Supuran CT

    更新日期：2004-06-21 00:00:00

  • Discovery of (E)-5-(benzylideneamino)-1H-benzo[d]imidazol-2(3H)-one derivatives as inhibitors for PTK6.

    abstract：:A lead compound 1, which inhibits the catalytic activity of PTK6, was selected from a chemical library. Derivatives of compound 1 were synthesized and analyzed for inhibitory activity against PTK6 in vitro and at the cellular level. Selected compounds were analyzed for cytotoxicity in human foreskin fibroblasts using ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.08.036

    authors： Shim HJ,Yang HR,Kim HI,Kang SA,No KT,Jung YH,Lee ST

    更新日期：2014-10-01 00:00:00

  • Discovery of a lead series of potent benzodiazepine 5-HT2C receptor agonists with high selectivity in functional and binding assays.

    abstract：:A series of potential new 5-HT2 receptor scaffolds based on a simplification of the clinically studied, 5-HT2CR agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.126929

    authors： Ren A,Zhu X,Feichtinger K,Lehman J,Kasem M,Schrader TO,Wong A,Dang H,Le M,Frazer J,Unett DJ,Grottick AJ,Whelan KT,Morgan ME,Sage CR,Semple G

    更新日期：2020-03-01 00:00:00

  • Preparation of difluoro analogs of CCGs and their pharmacological evaluations.

    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

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00338-2

    authors： Shibuya A,Sato A,Taguchi T

    更新日期：1998-08-04 00:00:00

  • Identification of CJC-1131-albumin bioconjugate as a stable and bioactive GLP-1(7-36) analog.

    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

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.06.066

    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

  • 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

    doi：10.1016/j.bmcl.2009.06.015

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

    更新日期：2009-08-01 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

    doi：10.1016/j.bmcl.2009.12.023

    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

  • Optimization of anti-proliferative activity using a screening approach with a series of bis-heterocyclic G-quadruplex ligands.

    abstract：:Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct aryl...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.07.057

    authors： Ohnmacht SA,Ciancimino C,Vignaroli G,Gunaratnam M,Neidle S

    更新日期：2013-10-01 00:00:00

  • Inhibitors of NF-kappaB derived from thalidomide.

    abstract：:A series of compounds originally derived from thalidomide were synthesized and evaluated. The most potent compounds in this series, 5HPP-33 and compound 20, inhibited NF-kappaB activation in HeLa cells. Preliminary study indicated that the mechanism of inhibition of NF-kappaB activation is through inhibition of its tr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.01.088

    authors： de-Blanco EJ,Pandit B,Hu Z,Shi J,Lewis A,Li PK

    更新日期：2007-11-01 00:00:00

  • In vitro biotransformations of the prostaglandin D2 (DP) antagonist MK-0524 and synthesis of metabolites.

    abstract：:Metabolites of the potent DP antagonist, MK-0524, were generated using in vitro systems including hepatic microsomes and hepatocytes. Four metabolites (two hydroxylated diastereomers, a ketone and an acyl glucuronide) were characterized by LC-MS/MS and 1H NMR. Larger quantities of these metabolites were prepared by ei...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.10.055

    authors： Nicoll-Griffith DA,Seto C,Aubin Y,Lévesque JF,Chauret N,Day S,Silva JM,Trimble LA,Truchon JF,Berthelette C,Lachance N,Wang Z,Sturino C,Braun M,Zamboni R,Young RN

    更新日期：2007-01-15 00:00:00

  • Synthesis and SAR of 5,6-diarylpyridines as human CB1 inverse agonists.

    abstract：:Structure-activity relationship studies for two series of 2-benzyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyridines having either a 3-cyano or 3-carboxamide moiety resulted in the preparation of the 2-(3,4-difluorobenzyloxy)-3-nitrile analog 10d and the 2-(3,4-difluorobenzyloxy)-3-(N-propylcarboxamide) analog 16c...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.11.031

    authors： Meurer LC,Finke PE,Mills SG,Walsh TF,Toupence RB,Debenham JS,Goulet MT,Wang J,Tong X,Fong TM,Lao J,Schaeffer MT,Chen J,Shen CP,Sloan Stribling D,Shearman LP,Strack AM,Van der Ploeg LH

    更新日期：2005-02-01 00:00:00