Synthesis and evaluation of potent pyrrolidine H(3) antagonists.

Abstract:

:The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyrrolidine ring was performed using pre-formatted precursor sets, where applicable, to afford several compounds with high affinity and selectivity for the H(3) receptor.

journal_name

Bioorg Med Chem Lett

authors

Vasudevan A,Conner SE,Gentles RG,Faghih R,Liu H,Dwight W,Ireland L,Kang CH,Esbenshade TA,Bennani YL,Hancock AA

doi

10.1016/s0960-894x(02)00685-6

subject

Has Abstract

pub_date

2002-11-04 00:00:00

pages

3055-8

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960894X02006856

journal_volume

12

pub_type

杂志文章
  • Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA.

    abstract::This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2006.11.081

    authors: Zhao Z,Wisnoski DD,O'Brien JA,Lemaire W,Williams DL Jr,Jacobson MA,Wittman M,Ha SN,Schaffhauser H,Sur C,Pettibone DJ,Duggan ME,Conn PJ,Hartman GD,Lindsley CW

    更新日期:2007-03-01 00:00:00

  • 5-benzylidenerhodanine and 5-benzylidene-2-4-thiazolidinedione based antibacterials.

    abstract::Herein we outline the antibacterial activity of amino acid containing thiazolidinediones and rhodanines against Gram-positive bacteria Staphylococcus aureus ATCC 31890, Staphylococcus epidermidis and Bacillus subtilis ATCC 6633. The rhodanine derivatives were generally more active than the analogous thiazolidinediones...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.02.100

    authors: Zvarec O,Polyak SW,Tieu W,Kuan K,Dai H,Pedersen DS,Morona R,Zhang L,Booker GW,Abell AD

    更新日期:2012-04-15 00:00:00

  • Synthesis and biological evaluation of novel heterocyclic quinones as inhibitors of the dual specificity protein phosphatase CDC25C.

    abstract::A focused set of heterocyclic quinones based on the benzothiazole, benzoxazole, benzimidazole, indazole and isoindole was prepared and screened with respect to the inhibition of the phosphatase activity of CDC25C. Benzoxazole- and benzothiazole-diones were at least 50 times more potent in inhibiting CDC25C than their ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.09.030

    authors: Lavergne O,Fernandes AC,Bréhu L,Sidhu A,Brézak MC,Prévost G,Ducommun B,Contour-Galcera MO

    更新日期:2006-01-01 00:00:00

  • Development of an affinity-driven cross-linker: isolation of a vitamin D receptor associated factor.

    abstract::A vitamin D analogue containing an affinity and a photoaffinity probe (affinity-driven cross-linker, Double Label) was synthesized. An unknown factor, associated with vitamin D receptor (VDR), was isolated from rat liver nuclear extract using a GST-VDR-ligand-binding domain fusion protein (GST-VDR-LBD), affinity label...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00009-3

    authors: Swamy N,Addo JK,Ray R

    更新日期:2000-02-21 00:00:00

  • Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series.

    abstract::Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2006.05.090

    authors: Petrov KG,Zhang YM,Carter M,Cockerill GS,Dickerson S,Gauthier CA,Guo Y,Mook RA Jr,Rusnak DW,Walker AL,Wood ER,Lackey KE

    更新日期:2006-09-01 00:00:00

  • Design and synthesis of bridged piperidine and piperazine isosteres.

    abstract::We have developed versatile methods toward the synthesis of a variety of piperidine/piperazine bridged isosteres of pridopidine. The compounds were assessed against the D2 receptor in agonist and antagonist modes and against the D4 receptor in agonist mode. hERG Binding and the ADME profiles were studied. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2018.06.038

    authors: Maertens G,Saavedra OM,Vece V,Reyes MAV,Hocine S,Öney E,Goument B,Mirguet O,Le Tiran A,Gloanec P,Hanessian S

    更新日期:2018-08-15 00:00:00

  • N-alkyl-4-piperidinyl-2,3-diarylpyrrole derivatives with heterocyclic substitutions as potent and broad spectrum anticoccidial agents.

    abstract::Diaryl-(4-piperidinyl)-pyrrole derivatives bearing cyclic amine substituents have been synthesized and evaluated as anticoccidial agents. Improvements in potency of Et-PKG inhibition, such as azetidine derivative 3a, and broad spectrum anticoccidial activities in feed, such as morpholine derivative 8c, have been achie...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2008.01.104

    authors: Liang GB,Qian X,Feng D,Fisher M,Crumley T,Darkin-Rattray SJ,Dulski PM,Gurnett A,Leavitt PS,Liberator PA,Misura AS,Samaras S,Tamas T,Schmatz DM,Wyvratt M,Biftu T

    更新日期:2008-03-15 00:00:00

  • Quantitative analysis of the kinetics of phospholipase A2 using fast atom bombardment mass spectrometry.

    abstract::Fast atom bombardment mass spectrometry that can directly analyze lysophospholipids was used to quantitatively determine the kinetics of phospholipase A2. This method is 1250 times more sensitive than the colorimetric assay. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(98)00750-1

    authors: Isomura S,Ito K,Haruna M

    更新日期:1999-02-08 00:00:00

  • Identification of a new biaryl scaffold generating potent renin inhibitors.

    abstract::The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar ren...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.07.127

    authors: Lacombe P,Aspiotis R,Bayly C,Chen A,Dubé D,Fortin R,Gallant M,Juteau H,Liu S,McKay D,Roy P,Wu T

    更新日期:2010-10-01 00:00:00

  • Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases.

    abstract::Miltirone analogues were synthesized and evaluated for inhibitory activity against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25 inhibitory activity, and several exhibited higher selectivity for Cdc25 than for PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against the tumo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.12.080

    authors: Huang W,Li J,Zhang W,Zhou Y,Xie C,Luo Y,Li Y,Wang J,Li J,Lu W

    更新日期:2006-04-01 00:00:00

  • Squalene-derived flexible linkers for bioactive peptides.

    abstract::A regiochemical and stereochemical mixture of flexible linkers bearing terminal azide functionality was synthesized in two steps from squalene and was used to connect two high affinity NDP-alpha-MSH ligands or two low affinity MSH(4) ligands. The ligands were N-terminally acylated using N-hydroxysuccinimidoyl 5-hexyno...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.04.001

    authors: Jagadish B,Sankaranarayanan R,Xu L,Richards R,Vagner J,Hruby VJ,Gillies RJ,Mash EA

    更新日期:2007-06-15 00:00:00

  • Parallel synthesis of acylsemicarbazide libraries: preparation of potent cyclin dependent kinase (cdk) inhibitors.

    abstract::Potent cyclin dependent kinase inhibitors were prepared using parallel synthesis methodology. Treating advanced intermediate 2 with a variety of hydrazides in DMSO at 80 degrees C for 30 min gave the desired acylsemicarbazides in good to excellent yield. Several compounds were active against cdk4/D1 and cdk2/E in the ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2004.09.023

    authors: Nugiel DA,Vidwans A,Dzierba CD

    更新日期:2004-11-15 00:00:00

  • Synthesis, biological evaluation and molecular modeling study of some new thiazolodiazepine analogs as CNS active agents.

    abstract::New derivatives of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124, 3), were synthesized as continuation to our previous patented efforts. Compounds 15 and 20 showed marginal hypnotic potency compared to 3. Compounds 15 (0.78mmol/kg) and 20 (0.39mmol/kg) showed remarkable 100% protec...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2015.11.097

    authors: Al-Rashood STA,Hassan GS,El-Messery SM,El-Taher KEH,Hefnawy MM,Al-Omar MA,El-Subbagh HI

    更新日期:2016-01-15 00:00:00

  • Antimitotic activity of structurally simplified biaryl analogs of the anticancer agents colchicine and combretastatin A4.

    abstract::Two substituted biaryl analogues of colchicine and combretastatin A4, readily available through a one-step, protecting group free Suzuki-Miyaura reaction were discovered to exhibit anticancer activity while simultaneously being of low cytotoxicity to noncancerous cell lines. The compounds were shown to initiate apopto...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2014.10.090

    authors: McNulty J,van den Berg S,Ma D,Tarade D,Joshi S,Church J

    更新日期:2015-01-01 00:00:00

  • Synthesis of a Streptococcus pyogenes vaccine candidate based on the M protein PL1 epitope.

    abstract::Group A streptococcus is a Gram-positive bacteria that causes a range of infectious diseases. Targeting the bacteria, a new self-adjuvanting vaccine candidate, incorporating a carbohydrate carrier and an amino acid-based adjuvant, was synthesised utilising carbohydrate chemistry and solid-phase peptide synthesis proce...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2008.12.013

    authors: Simerska P,Lu H,Toth I

    更新日期:2009-02-01 00:00:00

  • Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.

    abstract::Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites. In order to reduce attrition due to metabolism-induced toxicity and to improve the safety of drug candidates, we developed a simple cell viability assay by combining a bioactivation system (huma...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.06.088

    authors: Rana P,Will Y,Nadanaciva S,Jones LH

    更新日期:2016-08-15 00:00:00

  • Syntheses of sphingosine-1-phosphate stereoisomers and analogues and their interaction with EDG receptors.

    abstract::Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(02)00893-4

    authors: Lim HS,Oh YS,Suh PG,Chung SK

    更新日期:2003-01-20 00:00:00

  • Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A.

    abstract::Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2014.11.044

    authors: Nabika R,Suyama TL,Hau AM,Misu R,Ohno H,Ishmael JE,McPhail KL,Oishi S,Fujii N

    更新日期:2015-01-15 00:00:00

  • Dihydroquinolines as novel n-NOS inhibitors.

    abstract::Dihydroquinolines have been synthesized and have been shown to be potent n-NOS inhibitors. Selectivity versus e-NOS was increased to approximately 100-fold through appropriate substitution at the benzene ring. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(02)00481-x

    authors: Jaroch S,Hölscher P,Rehwinkel H,Sülzle D,Burton G,Hillmann M,McDonald FM

    更新日期:2002-09-16 00:00:00

  • Syntheses and antifungal activity of pseudomycin side-chain analogues. Part 1.

    abstract::We have described herein the syntheses of three novel series of aromatic ring containing pseudomycin side-chain analogues. Preliminary biological evaluations of these analogues clearly indicate that it is possible to synthesize rigid pseudomycin side-chain analogues without compromising in vitro antifungal activity. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00423-6

    authors: Jamison J,Levy S,Sun X,Zeckner D,Current W,Zweifel M,Rodriguez M,Turner W,Chen SH

    更新日期:2000-09-18 00:00:00

  • Nitrone derivatives of trolox as neuroprotective agents.

    abstract::Synthesis of nitrone derivatives of trolox is described. Their biological evaluation was performed in vitro for scavenging different free radicals, inhibiting Fe(2+)-induced lipid peroxidation, and in vivo in a permanent middle cerebral artery occlusion model in mice. New compounds exert pharmacological activities com...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.04.043

    authors: Balogh GT,Vukics K,Könczöl A,Kis-Varga A,Gere A,Fischer J

    更新日期:2005-06-15 00:00:00

  • Synthesis and preliminary cytotoxicity of nitrogen mustard derivatives of distamycin A.

    abstract::Distamycin and nitrogen mustard conjugates, in which the nitrogen mustard unit was coupled to the C-terminus of the pyrrole, were synthesized. The switching of the nitrogen mustard unit from the N-terminus to the C-terminus did not compromise the compound's cytotoxicity. Compound 3, bearing three pyrrole units, was hi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(02)00986-1

    authors: Wang Y,Wright SC,Larrick JW

    更新日期:2003-02-10 00:00:00

  • N-(pyrimidin-4-yl) and N-(pyridin-2-yl) phenylalanine derivatives as VLA-4 integrin antagonists.

    abstract::The SAR studies to optimise both potency and rate of clearance in the rat for a series of pyrimidine and pyridine based VLA-4 antagonists are described. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(02)00241-x

    authors: Porter JR,Archibald SC,Brown JA,Childs K,Critchley D,Head JC,Hutchinson B,Parton TA,Robinson MK,Shock A,Warrellow GJ,Zomaya A

    更新日期:2002-06-17 00:00:00

  • An approach for differentiating isozymes. Construction of libraries containing short aromatic peptides as part of a method to design selective inhibitors against lipases.

    abstract::Through synthesis and assays of peptidyl substrates, we could select substrates having peptidyl complementary against lipases. The best substrate showed 20-fold improved K(m) relative to non-peptidyl substrate. Using this information, we generated selective inhibitors. Lipase activities with peptidyl substrates were r...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.03.048

    authors: Park S,Yu J

    更新日期:2012-05-01 00:00:00

  • Modulation of binding properties of amphiphilic DNA containing multiple dodecyl phosphotriester linkages to lipid bilayer membrane.

    abstract::DNA is a promising functional molecule to modify and design lipid membrane functions. In order to use DNA in a hydrophilic-hydrophobic interface including lipid membrane, we have developed an amphiphilic DNA having dodecyl phosphotriester linkages (dod-DNA). Herein, we report the binding of a series of amphiphilic dod...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2014.05.042

    authors: Makishi S,Shibata T,Okazaki M,Dohno C,Nakatani K

    更新日期:2014-08-01 00:00:00

  • Secoiridoid glucosides and related compounds from Syringa reticulata and their antioxidant activities.

    abstract::A 70% EtOH extract from the bark of Syringareticulata has shown significant antioxidant activity. Chemical study on the extract resulted in the isolation of seventeen compounds (1-17), including a novel oleoside-type secoiridoid glucoside, reticuloside (1), and the structures were elucidated on the basis of extensive ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.08.089

    authors: Bi X,Li W,Sasaki T,Li Q,Mitsuhata N,Asada Y,Zhang Q,Koike K

    更新日期:2011-11-01 00:00:00

  • trans-3,4-Disubstituted pyrrolidines as inhibitors of the human aspartyl protease renin. Part II: prime site exploration using an oxygen linker.

    abstract::Inhibition of the aspartyl protease renin is considered as an efficient approach for treating hypertension. Lately, we described the discovery of a novel class of direct renin inhibitors which comprised a pyrrolidine scaffold (e.g., 2). Based on the X-ray structure of the lead compound 2 bound to renin we predicted th...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2015.02.040

    authors: Sellner H,Cottens S,Cumin F,Ehrhardt C,Kosaka T,Lorthiois E,Ostermann N,Webb RL,Rigel DF,Wagner T,Maibaum J

    更新日期:2015-04-15 00:00:00

  • C1 and N5 derivatives of cerpegin: synthesis of a new series based on structure-activity relationships to optimize their inhibitory effect on 20S proteasome.

    abstract::Thirty-two new derivatives of cerpegin (1,1,5-trimethylfuro[3,4-c]pyridine-3,4-dione) were designed and synthesized in high yield by a new method, combining several C(1) and N(5) substituents. All compounds were tested for their inhibitory effect on the CT-L, T-L and PA proteolytic activities of a purified mammalian 2...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.02.079

    authors: Hovhannisyan A,Pham TH,Bouvier D,Qin L,Melikyan G,Reboud-Ravaux M,Bouvier-Durand M

    更新日期:2013-05-01 00:00:00

  • Discovery and optimization of 2-aminopyridine derivatives as novel and selective JAK2 inhibitors.

    abstract::Janus kinases (JAKs) including JAK1, JAK2, JAK3, and TYK2 are members of a family of intracellular nonreceptor tyrosine kinases, which have been demonstrated to be critical in the cell signaling pathway and involved in inflammatory diseases and cancer. V617F mutation in JAK2 has been implicated in polycythaemia vera (...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127048

    authors: Ma X,Diao Y,Ge H,Xu F,Zhu L,Zhao Z,Li H

    更新日期:2020-04-15 00:00:00

  • Anti-HIV properties of cationic fullerene derivatives.

    abstract::A series of regioisomeric bis-fulleropyrrolidines bearing two ammonium groups have been synthesized and their activities against HIV-1 and HIV-2 have been evaluated. Two trans isomers have been endowed with interesting antiviral properties, confirming the importance of the relative positions of the substituent on the ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.05.069

    authors: Marchesan S,Da Ros T,Spalluto G,Balzarini J,Prato M

    更新日期:2005-08-01 00:00:00