当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Some analogues of luteinizing hormone-releasing hormone with substituents in position 10.

Some analogues of luteinizing hormone-releasing hormone with substituents in position 10.

Abstract：

:As part of our studies on the design of agonists of the luteinizing hormone-releasing hormone (LH-RH), we have synthesized the [des-Gly-NH2(10)]-LH-RH N-methylhydrazide (1), the corresponding thiosemicarbazide (2), and the N-formyl- (3) N-acetyl- (4) and N-(trifluoroacetyl)hydrazide (5). Analogue 1 may be regarded as isosteric with [des-Gly-NH2(10)]-LH-RH N-alkylamides which are, in general, potent agonists. Analogues 2-5 may be regarded as isosteric with [aza-Gly-NH2(10)]-OH-RH, which is equipotent with the hormone. The required protected intermediates were prepared by solid-phase synthesis, and the free peptides were prepared from them by deprotection with HF, followed by purification on Sephadex G-25. Bioassay of these analogues with rat hemipituitaries in vitro showed the following values as percentages of the hormonal values for the release of LH and FSH respectively: N-methylhydrazide (1), 17 and 11%; semithiocarbazide (2), 6.5 and 4.6%; N-formylhydrazide (3), 15.3 and 10%; N-acetylhydrazide (4), 1.2 and 0.6%; N-(trifluoroacetyl)hydrazide (5), 1.0 and 0.9%. Thus, these types of isosteric substitutions are inimical to the preservation of the high biological activity of LH-RH.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Nakagawa SH,Yang DC,Flouret G

doi

10.1021/jm00134a021

subject

Has Abstract

pub_date

1981-02-01 00:00:00

pages

221-3

issue

2

eissn

0022-2623

issn

1520-4804

journal_volume

24

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures.

    abstract：:Screening in mixtures is a common approach for increasing the efficiency of high-throughput screening. Here we investigate how the "compound load" of mixtures influences promiscuous aggregate-based inhibition. We screened 764 molecules individually and in mixtures of 10 at 5 miccroM each, comparing the observed inhibi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060029z

    authors： Feng BY,Shoichet BK

    更新日期：2006-04-06 00:00:00

  • Damicoside from Axinella damicornis: the influence of a glycosylated galactose 4-OH group on the immunostimulatory activity of alpha-galactoglycosphingolipids.

    abstract：:Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory glycosphingolipids from marine sponges. Analysis of the glycosphingolipid composition of the marine sponge Axinella damicornis revealed the presence of a new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a glycosylated g...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm050506y

    authors： Costantino V,D'Esposito M,Fattorusso E,Mangoni A,Basilico N,Parapini S,Taramelli D

    更新日期：2005-11-17 00:00:00

  • Isosorbide-2-benzyl carbamate-5-salicylate, a peripheral anionic site binding subnanomolar selective butyrylcholinesterase inhibitor.

    abstract：:Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9014845

    authors： Carolan CG,Dillon GP,Khan D,Ryder SA,Gaynor JM,Reidy S,Marquez JF,Jones M,Holland V,Gilmer JF

    更新日期：2010-02-11 00:00:00

  • Discovery of New H2S Releasing Phosphordithioates and 2,3-Dihydro-2-phenyl-2-sulfanylenebenzo[d][1,3,2]oxazaphospholes with Improved Antiproliferative Activity.

    abstract：:Hydrogen sulfide (H2S) is now recognized as a physiologically important gasotransmitter. Compounds which release H2S slowly are sought after for their potential in therapy. Herein the synthesis of a series of phosphordithioates based on 1 (GYY4137) are described. Their H2S release profiles are characterized using 2,6-...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00848

    authors： Feng W,Teo XY,Novera W,Ramanujulu PM,Liang D,Huang D,Moore PK,Deng LW,Dymock BW

    更新日期：2015-08-27 00:00:00

  • Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration

    abstract：:This paper describes an extended structure-activity relationships study of aminotetralin-piperazine-based hybrid molecules developed earlier for dopamine D2/D3 receptors. Various analogues as positional isomers have been developed where location of the phenolic hydroxyl group has been varied on the aromatic ring. Betw...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070860r

    authors： Biswas S,Zhang S,Fernandez F,Ghosh B,Zhen J,Kuzhikandathil E,Reith ME,Dutta AK

    更新日期：2008-01-10 00:00:00

  • Potent and selective conformationally restricted neuronal nitric oxide synthase inhibitors.

    abstract：:Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides and some peptidomimetic analogues as potent and selective inhibitors of neuronal NOS (nNOS). Here we...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030297m

    authors： Gómez-Vidal JA,Martásek P,Roman LJ,Silverman RB

    更新日期：2004-01-29 00:00:00

  • Synthesis and biochemical evaluation of adenosylspermidine, a nucleoside-polyamine adduct inhibitor of spermidine synthase.

    abstract：:The synthesis of a new class of multisubstrate adduct inhibitors of polyamine biosynthesis has been investigated. The first target compound, designed to inhibit spermidine synthase, was obtained and proved to be a very potent inhibitor of that enzyme. Two synthetic routes to effect the coupling of the polyamine spermi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00014a023

    authors： Lakanen JR,Pegg AE,Coward JK

    更新日期：1995-07-07 00:00:00

  • Inhibitors of human renin with C-termini derived from amides and esters of alpha-mercaptoalkanoic acids.

    abstract：:New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cycl...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00093a009

    authors： Ashton WT,Cantone CL,Tolman RL,Greenlee WJ,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

    更新日期：1992-07-24 00:00:00

  • Design and Synthesis of Bitopic 2-Phenylcyclopropylmethylamine (PCPMA) Derivatives as Selective Dopamine D3 Receptor Ligands.

    abstract：:2-Phenylcyclopropylmethylamine (PCPMA) analogues have been reported as selective serotonin 2C agonists. On the basis of the same scaffold, we designed and synthesized a series of bitopic derivatives as dopamine D3R ligands. A number of these new compounds show a high binding affinity for D3R with excellent selectivity...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01835

    authors： Tan L,Zhou Q,Yan W,Sun J,Kozikowski AP,Zhao S,Huang XP,Cheng J

    更新日期：2020-05-14 00:00:00

  • Toward development of targeted nonsteroidal antiandrogen-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-gadolinium complex for prostate cancer diagnostics.

    abstract：:Androgen receptors are present in most advanced prostate cancer specimens, having a critical role in development of this type of cancer. For correct prognosis of patient conditions and treatment monitoring, noninvasive imaging techniques have great advantages over surgical procedures. We developed synthetic methodolog...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100289b

    authors： Marom H,Miller K,Bechor-Bar Y,Tsarfaty G,Satchi-Fainaro R,Gozin M

    更新日期：2010-09-09 00:00:00

  • Pyridyl-2,5-diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists: synthesis, pharmacokinetics, and in vivo potency.

    abstract：:A six-stage stereoselective synthesis of indanyl-7-(3'-pyridyl)-(3R,6R,7R)-2,5-diketopiperazines oxytocin antagonists from indene is described. SAR studies involving mono- and disubstitution in the 3'-pyridyl ring and variation of the 3-isobutyl group gave potent compounds (pK(i) > 9.0) with good aqueous solubility. E...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm201287w

    authors： Borthwick AD,Liddle J,Davies DE,Exall AM,Hamlett C,Hickey DM,Mason AM,Smith IE,Nerozzi F,Peace S,Pollard D,Sollis SL,Allen MJ,Woollard PM,Pullen MA,Westfall TD,Stanislaus DJ

    更新日期：2012-01-26 00:00:00

  • A comparative molecular field analysis model for 6-arylpyrrolo[2,1-d] [1,5]benzothiazepines binding selectively to the mitochondrial benzodiazepine receptor.

    abstract：:A series of 42 6-arylpyrrolo[2,1-d][1,5]benzothiazepines, which we have recently described as selective ligands of the mitochondrial benzodiazepine receptor (MBR) (Fiorini I.; et al. J. Med. Chem. 1994, 37, 1427-1438), have been investigated using the comparative molecular field analysis (CoMFA) approach. The resultin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00050a007

    authors： Greco G,Novellino E,Fiorini I,Nacci V,Campiani G,Ciani SM,Garofalo A,Bernasconi P,Mennini T

    更新日期：1994-11-25 00:00:00

  • A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth.

    abstract：:Focal adhesion kinase (FAK) is a nonreceptor kinase that is overexpressed in many types of tumors. We developed a novel cancer-therapy approach, targeting the main autophosphorylation site of FAK, Y397, by computer modeling and screening of the National Cancer Institute (NCI) small molecule compounds database. More th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm800483v

    authors： Golubovskaya VM,Nyberg C,Zheng M,Kweh F,Magis A,Ostrov D,Cance WG

    更新日期：2008-12-11 00:00:00

  • Angiotensin converting enzyme inhibitors: 1,5-benzothiazepine derivatives.

    abstract：:The synthesis of chiral 1,5-benzothiazepines 2a-c, 14a-c, 15c, and 16a prepared from cysteine is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound. Compound 2c was the most potent in vitro having an IC50 of 2.95 nM. The ester of 2c, i.e. 14c, was found to inhibit the A...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00148a024

    authors： Slade J,Stanton JL,Ben-David D,Mazzenga GC

    更新日期：1985-10-01 00:00:00

  • Peripheral and axial substitution of phthalocyanines with solketal groups: synthesis and in vitro evaluation for photodynamic therapy.

    abstract：:Phthalocyanines (Pcs) are a class of photosensitizers (PSs) with a strong tendency to aggregate in aqueous environment, which has a negative influence on their photosensitizing ability in photodynamic therapy. Pcs with either peripheral or axial solketal substituents, that is, ZnPc(sol)8 and Si(sol)2Pc, respectively, ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm061136w

    authors： Hofman JW,van Zeeland F,Turker S,Talsma H,Lambrechts SA,Sakharov DV,Hennink WE,van Nostrum CF

    更新日期：2007-04-05 00:00:00

  • Anti-inflammatory active gold(I) complexes involving 6-substituted-purine derivatives.

    abstract：:The gold(I) complexes of the general formula [Au(L(n))(PPh(3))]·xH(2)O (1-8; n = 1-8 and x = 0-1.5), where L(n) stands for a deprotonated form of the benzyl-substituted derivatives of 6-benzylaminopurine, were prepared, thoroughly characterized (elemental analyses, FT-IR, Raman and multinuclear NMR spectroscopy, ESI+ ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm201416p

    authors： Trávníček Z,Starha P,Vančo J,Silha T,Hošek J,Suchý P Jr,Pražanová G

    更新日期：2012-05-24 00:00:00

  • Synthesis and Characterization of Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Antibacterial Activity against Gram-Negative Bacteria.

    abstract：:There is an urgent unmet medical need for novel antibiotics that are effective against a broad range of bacterial species, especially multidrug resistant ones. Tetrahydropyran-based inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) display potent activity against Gram-positive pathogens ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01831

    authors： Surivet JP,Zumbrunn C,Bruyère T,Bur D,Kohl C,Locher HH,Seiler P,Ertel EA,Hess P,Enderlin-Paput M,Enderlin-Paput S,Gauvin JC,Mirre A,Hubschwerlen C,Ritz D,Rueedi G

    更新日期：2017-05-11 00:00:00

  • Extraordinarily potent antimalarial compounds: new, structurally simple, easily synthesized, tricyclic 1,2,4-trioxanes.

    abstract：:New, racemic, tricyclic trioxane alcohol 3 was designed and synthesized as a structurally simple analog of clinically useful, tetracyclic, antimalarial artemisinin. A series of 20 ester and ether derivatives of alcohol 3 were prepared easily, without destruction of the essential trioxane system. Chemical structure-ant...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00091a014

    authors： Posner GH,Oh CH,Gerena L,Milhous WK

    更新日期：1992-06-26 00:00:00

  • Predicting binding modes from free energy calculations.

    abstract：:To produce reliable predictions of bioactive conformations is a major challenge in the field of structure-based inhibitor design and is a requirement for accurate binding free energy predictions with structure-based methods. A series of HIV-1 reverse transcriptase inhibitors was cross-docked using a non-native crystal...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701218j

    authors： Nervall M,Hanspers P,Carlsson J,Boukharta L,Aqvist J

    更新日期：2008-05-08 00:00:00

  • The cis-4-amino-L-proline residue as a scaffold for the synthesis of cyclic and linear endomorphin-2 analogues.

    abstract：:Endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) is an endogenous tetrapeptide that combines potency and efficacy with high affinity and selectivity toward the μ opioid receptor, the most responsible for analgesic effects in the central nervous system. The presence of the Pro(2) represents a crucial factor for the ligand s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm201402v

    authors： Mollica A,Pinnen F,Stefanucci A,Feliciani F,Campestre C,Mannina L,Sobolev AP,Lucente G,Davis P,Lai J,Ma SW,Porreca F,Hruby VJ

    更新日期：2012-04-12 00:00:00

  • Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors.

    abstract：:In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm015545y

    authors： López-Rodríguez ML,Viso A,Ortega-Gutiérrez S,Lastres-Becker I,González S,Fernández-Ruiz J,Ramos JA

    更新日期：2001-12-20 00:00:00

  • Piperazinylquinoxalines with central serotoninmimetic activity.

    abstract：:Regioselective syntheses of substituted 2-chloroquinoxalines and derived 2-(1-piperazinyl)quinoxalines are described. Selectivity in regards to serotonin reuptake blocking and serotoninmimetic activities of the piperazinylquinoxalines is reported. In general, introduction of a 6-substituent into the piperazinylquinoxa...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00133a019

    authors： Lumma WC Jr,Hartman RD,Saari WS,Engelhardt EL,Lotti VJ,Stone CA

    更新日期：1981-01-01 00:00:00

  • Nucleosides and nucleotides. 200. Reinvestigation of 5'-N-ethylcarboxamidoadenosine derivatives: structure-activity relationships for P(3) purinoceptor-like proteins.

    abstract：:The non-P(1) and non-P(2) muscle relaxant effect of ATP in rabbit thoracic aorta has recently been attributed to a putative P(3) purinoceptor, which is activated by either adenosine or ATP. Since the physiological roles of this putative P(3) purinoceptor and of a new [(3)H]-5'-N-ethylcarboxamidoadenosine (NECA)-bindin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000150k

    authors： Umino T,Yoshioka K,Saitoh Y,Minakawa N,Nakata H,Matsuda A

    更新日期：2001-01-18 00:00:00

  • Novel tropane-based irreversible ligands for the dopamine transporter.

    abstract：:3alpha-(diphenylmethoxy)tropane (benztropine) and its analogues are tropane ring-containing dopamine uptake inhibitors that display binding and behavioral profiles that are distinct from cocaine. We previously prepared a benztropine-based photoaffinity label [125I]-(N-[4-(4'-azido-3'-iodophenyl)butyl]-3alpha-[bis(4'-f...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0101904

    authors： Zou MF,Kopajtic T,Katz JL,Wirtz S,Justice JB Jr,Newman AH

    更新日期：2001-12-06 00:00:00

  • Molecular modeling and molecular dynamics simulation of the human A2B adenosine receptor. The study of the possible binding modes of the A2B receptor antagonists.

    abstract：:A molecular model of the human A(2B) adenosine receptor containing seven transmembrane alpha helices connected by three intracellular and three extracellular hydrophilic loops had been constructed. A molecular docking of seven structurally diverse xanthine antagonists of the A(2B) receptor was performed, and the diffe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049418o

    authors： Ivanov AA,Baskin II,Palyulin VA,Piccagli L,Baraldi PG,Zefirov NS

    更新日期：2005-11-03 00:00:00

  • Discovery and investigation of antiproliferative and apoptosis-inducing properties of new heterocyclic podophyllotoxin analogues accessible by a one-step multicomponent synthesis.

    abstract：:Podophyllotoxin has been extensively used as a lead agent in the development of new anticancer drugs. On the basis of the previously reported simplified 4-aza-2,3-didehydro podophyllotoxin analogues, we implemented a bioisosteric replacement of the methylenedioxybenzene subunit with a pyrazole moiety to afford tetracy...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070528f

    authors： Magedov IV,Manpadi M,Slambrouck SV,Steelant WF,Rozhkova E,Przheval'skii NM,Rogelj S,Kornienko A

    更新日期：2007-10-18 00:00:00

  • Imidazolopiperazines: hit to lead optimization of new antimalarial agents.

    abstract：:Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm2003359

    authors： Wu T,Nagle A,Kuhen K,Gagaring K,Borboa R,Francek C,Chen Z,Plouffe D,Goh A,Lakshminarayana SB,Wu J,Ang HQ,Zeng P,Kang ML,Tan W,Tan M,Ye N,Lin X,Caldwell C,Ek J,Skolnik S,Liu F,Wang J,Chang J,Li C,Hollenbe

    更新日期：2011-07-28 00:00:00

  • X-ray Structures of Target-Ligand Complexes Containing Compounds with Assay Interference Potential.

    abstract：:Pan assay interference compounds (PAINS) have become a paradigm for compound classes that might cause artifacts in biological assays. PAINS-defining substructures are typically contained in larger compounds. We have systematically examined X-ray structures of protein-ligand complexes for compounds containing PAINS mot...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b01780

    authors： Gilberg E,Gütschow M,Bajorath J

    更新日期：2018-02-08 00:00:00

  • Discovery of Novel Pyrazole-Based Selective Aldosterone Synthase (CYP11B2) Inhibitors: A New Template to Coordinate the Heme-Iron Motif of CYP11B2.

    abstract：:It is necessary for aldosterone synthase (CYP11B2) inhibitors to have both high potency and high selectivity over 11β-hydroxylase (CYP11B1), a critical enzyme for cortisol synthesis. Previous studies have reported a number of CYP11B2 inhibitors, most of which have an imidazole or pyridine ring to coordinate the heme-i...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b00328

    authors： Sakakibara R,Sasaki W,Onda Y,Yamaguchi M,Ushirogochi H,Hiraga Y,Sato K,Nishio M,Egi Y,Takedomi K,Shimizu H,Ohbora T,Akahoshi F

    更新日期：2018-07-12 00:00:00

  • Structure-activity studies of reduced-size gonadotropin-releasing hormone agonists derived from the sequence of an endothelin antagonist.

    abstract：:We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990432o

    authors： Yahalom D,Rahimipour S,Koch Y,Ben-Aroya N,Fridkin M

    更新日期：2000-07-27 00:00:00