New opioid designed multiple ligand from Dmt-Tic and morphinan pharmacophores.

abstract：:In a recent paper (Colotta et al. J. Med. Chem. 2000, 43, 1158-1164) we reported the synthesis and adenosine receptor binding activity of two sets of 2-aryl-1,2,4-triazolo[4,3-a]quinoxalines (A and B) some of which were potent and selective A(1) or A(3) antagonists. In this paper the synthesis of a set of 2-arylpyrazo...

journal_title：Journal of medicinal chemistry

authors： Colotta V,Catarzi D,Varano F,Cecchi L,Filacchioni G,Martini C,Trincavelli L,Lucacchini A

更新日期：2000-08-10 00:00:00

abstract：:The prevalence of multidrug resistance among clinically significant bacterial pathogens underscores a critical need for the development of new classes of antibiotics with novel mechanisms of action. Here we describe the synthesis and evaluation of a guanidinomethyl biaryl compound {1-((4'-(tert-butyl)-[1,1'-biphenyl]-...

journal_title：Journal of medicinal chemistry

authors： Kaul M,Parhi AK,Zhang Y,LaVoie EJ,Tuske S,Arnold E,Kerrigan JE,Pilch DS

更新日期：2012-11-26 00:00:00

abstract：:The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a no...

journal_title：Journal of medicinal chemistry

authors： Kerwin JF Jr,Wagenaar F,Kopecka H,Lin CW,Miller T,Witte D,Stashko M,Nadzan AM

更新日期：1991-12-01 00:00:00

abstract：:Members of the Wee family of kinases negatively regulate the cell cycle via phosphorylation of CDK1 and are considered potential drug targets. Herein, we investigated the structure-function relationship of human Wee1, Wee2, and Myt1 (PKMYT1). Purified recombinant full-length proteins and kinase domain constructs diffe...

journal_title：Journal of medicinal chemistry

authors： Zhu JY,Cuellar RA,Berndt N,Lee HE,Olesen SH,Martin MP,Jensen JT,Georg GI,Schönbrunn E

更新日期：2017-09-28 00:00:00

abstract：:The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) mod...

journal_title：Journal of medicinal chemistry

authors： Abd El-Salam M,Bastos JK,Han JJ,Previdi D,Coelho EB,Donate PM,Romero MF,Lieske J

更新日期：2018-02-22 00:00:00

abstract：:ACTIBIND and its human homologue RNASET2 are T2 ribonucleases (RNases). RNases are ubiquitous and efficient enzymes that hydrolyze RNA to 3' mononucleotides and also possess antitumorigenic and antiangiogenic activities. Previously, we have shown that ACTIBIND and RNASET2 bind actin and interfere with the cytoskeletal...

journal_title：Journal of medicinal chemistry

authors： de Leeuw M,González A,Lanir A,Roiz L,Smirnoff P,Schwartz B,Shoseyov O,Almog O

更新日期：2012-02-09 00:00:00

abstract：:Idiopathic pulmonary fibrosis (IPF) is a rare and devastating chronic lung disease of unknown etiology. Despite the approved treatment options nintedanib and pirfenidone, the medical need for a safe and well-tolerated antifibrotic treatment of IPF remains high. The human prostaglandin F receptor (hFP-R) is widely expr...

journal_title：Journal of medicinal chemistry

authors： Beck H,Thaler T,Meibom D,Meininghaus M,Jörißen H,Dietz L,Terjung C,Bairlein M,von Bühler CJ,Anlauf S,Fürstner C,Stellfeld T,Schneider D,Gericke KM,Buyck T,Lovis K,Münster U,Anlahr J,Kersten E,Levilain G,Marossek V

更新日期：2020-10-22 00:00:00

abstract：:Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a...

journal_title：Journal of medicinal chemistry

authors： Kánai K,Arányi P,Böcskei Z,Ferenczy G,Harmat V,Simon K,Bátori S,Náray-Szabo G,Hermecz I

更新日期：2008-12-11 00:00:00

abstract：:Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leu...

journal_title：Journal of medicinal chemistry

authors： Nagasawa HT,Elberling JA,Shirota FN

更新日期：1975-08-01 00:00:00

abstract：:A series of S-alkylated derivatives of 5-mercapto-2'-deoxyuridine have been prepared by alkylation of the preformed nucleoside. Two of these compounds, the S-propargyl and S-allyl derivatives, have shown significant antiviral activity against Herpes simplex type 1 in HeLa TK- cells but appear to be less effective in t...

journal_title：Journal of medicinal chemistry

authors： Dinan FJ,Bardos TJ

更新日期：1980-05-01 00:00:00

abstract：:This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported. Here structure-based virtual screening was performed to search for the inhibitors from an in-house...

journal_title：Journal of medicinal chemistry

authors： Hu G,Li X,Zhang X,Li Y,Ma L,Yang LM,Liu G,Li W,Huang J,Shen X,Hu L,Zheng YT,Tang Y

更新日期：2012-11-26 00:00:00

abstract：:6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring ...

journal_title：Journal of medicinal chemistry

authors： Nakagawa-Goto K,Chang PC,Lai CY,Hung HY,Chen TH,Wu PC,Zhu H,Sedykh A,Bastow KF,Lee KH

更新日期：2010-09-23 00:00:00

abstract：:A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of s...

journal_title：Journal of medicinal chemistry

authors： Kim HK,Kang MK,Jung KH,Kang SH,Kim YH,Jung JC,Lee GH,Chang Y,Kim TJ

更新日期：2013-10-24 00:00:00

abstract：:High throughput screening and subsequent optimization led to the discovery of novel quaternary ammonium salts as highly potent muscarinic acetylcholine receptor antagonists with excellent selectivity. Compounds 8a, 13a, and 13b showed excellent inhibitory activity and long duration of action in bronchoconstriction in ...

journal_title：Journal of medicinal chemistry

authors： Jin J,Wang Y,Shi D,Wang F,Davis RS,Jin Q,Fu W,Foley JJ,Webb EF,Dehaas CJ,Berlanga M,Burman M,Sarau HM,Morrow DM,Rao P,Kallal LA,Moore ML,Rivero RA,Palovich M,Salmon M,Belmonte KE,Busch-Petersen J

更新日期：2008-08-28 00:00:00

abstract：:A new class of histamine analogues characterized by a 3, 3-diphenylpropyl substituent at the 2-position of the imidazole nucleus has been prepared outgoing from 4,4-diphenylbutyronitrile (4b) via cyclization of the corresponding methyl imidate 5b with 2-oxo-4-phthalimido-1-butyl acetate or 2-oxo-1,4-butandiol in liqui...

journal_title：Journal of medicinal chemistry

authors： Elz S,Kramer K,Pertz HH,Detert H,ter Laak AM,Kühne R,Schunack W

更新日期：2000-03-23 00:00:00

abstract：:A series of regioisomeric substituted 6-O-benzyl ethers of 6 beta-naltrexol (12) in which isothiocyanate groups were attached directly to or one carbon removed from the aromatic ring of the benzyl group were prepared. These agents were prepared to obtain electrophilic opioid ligands potentially useful in the character...

journal_title：Journal of medicinal chemistry

authors： Davis RD,Nelson WL

更新日期：1995-02-03 00:00:00

abstract：:New analogues of human cholecystokinin in which the Tyr(SO3H) has been replaced by Phe(p-CH2SO3Na), methionines by norleucines, and tryptophan by 2-naphthylalanine([Phe(p-CH2- SO3Na)27,Nle28,31,Nal30]-CCK26-33 and [Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33) were synthesized by Fmoc solid phase methodology on two diff...

journal_title：Journal of medicinal chemistry

authors： Miranda MT,Liddle RA,Rivier JE

更新日期：1993-06-11 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) of a series of 6-anilinouracil derivatives were developed for their inhibitory activity against the wild-type DNA polymerase III (pol III) and a mutant enzyme, pol III/azp-12, derived from Bacillus subtilis. Interaction between inhibitors and both enzymes appears to...

journal_title：Journal of medicinal chemistry

authors： Wright GE,Gambino JJ

更新日期：1984-02-01 00:00:00

abstract：:A new family of chelating agents based on 4-(substituted-carbamoyl)-3-hydroxy-2-pyridinones is reported. These have optional terminal substituents on the nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular backbones through amide linkages. A very important feature of the methyl-substituted liga...

journal_title：Journal of medicinal chemistry

authors： Xu J,Kullgren B,Durbin PW,Raymond KN

更新日期：1995-07-07 00:00:00

abstract：:HP-236 (3-[4-[4-(6-Fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate; P-9236) (54) displayed a pharmacological profile indicative of potential atypical antipsychotic activity. A series of piperazinyl butyl thiazolidinones structurally related to this compound were prepared and ev...

journal_title：Journal of medicinal chemistry

authors： Hrib NJ,Jurcak JG,Bregna DE,Burgher KL,Hartman HB,Kafka S,Kerman LL,Kongsamut S,Roehr JE,Szewczak MR,Woods-Kettelberger AT,Corbett R

更新日期：1996-09-27 00:00:00

abstract：:A series of structurally different Gd(III) conjugates incorporating a bile acid moiety have been prepared. Polyaminopolycarboxylic ligands such as diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) have been selected as chelating subunit for the Gd(III) ion. Ch...

journal_title：Journal of medicinal chemistry

authors： Anelli PL,Lattuada L,Lorusso V,Lux G,Morisetti A,Morosini P,Serleti M,Uggeri F

更新日期：2004-07-01 00:00:00

abstract：:Dideoxy- and trideoxynucleosides of 5-fluorouracil have been synthesized for antitumor evaluation. 2',5'-Dideoxy-5-fluorouridine (3) was prepared from 2'-deoxy-5-fluorouridine (1) by iodination using methyltriphenoxyphosponium iodide, followed by catalytic reduction. 1-(2',5'-Dideoxy-beta-D-threo-pentofuranosyl)5-fluo...

journal_title：Journal of medicinal chemistry

authors： Cook AF,Holman MJ,Kramer MJ

更新日期：1980-08-01 00:00:00

abstract：:A series of 62 diarylamidine derivatives was evaluated for their antiproteolytic activity. In all but two of the compounds one or both of the amidino-substituted aryl moieties was either an indole or an indole-like ring. The latter included indene, benzimidazole, benzofuran, benzol[beta]thiophene, and several other re...

journal_title：Journal of medicinal chemistry

authors： Tidwell RR,Geratz JD,Dann O,Volz G,Zeh D,Loewe H

更新日期：1978-07-01 00:00:00

abstract：:To evaluate nonaromatic catechol bioisosteres, the conformationally restrained enynes 1 and enediynes 2 were synthesized via palladium-catalyzed coupling as the key reaction step. Subsequent receptor binding studies at the dopamine receptor subtypes D(1), D(2 long), D(2 short), D(3), and D(4) showed highly interesting...

journal_title：Journal of medicinal chemistry

authors： Hübner H,Haubmann C,Utz W,Gmeiner P

更新日期：2000-02-24 00:00:00

abstract：:A series of new 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties. A number of these compounds are extremely active against Plasmodium berghei in the mouse. Some structural requirements for optimal efficacy are considered. ...

journal_title：Journal of medicinal chemistry

authors： Nodiff EA,Saggiomo AJ,Tanabe K,Chen EH,Shinbo M,Tyagi MP,Kozuka A,Otomasu H,Verma BL,Goff D

更新日期：1975-10-01 00:00:00

abstract：:Compounds acting via the neurotensin receptor type 2 (NTS2) are known to be active in animal models of acute and chronic pain. To identify novel NTS2 selective analgesics, we searched for NTS2 selective nonpeptide compounds using a FLIPR assay and identified the title compound (NTRC-824, 5) that, to our knowledge, is ...

journal_title：Journal of medicinal chemistry

authors： Thomas JB,Giddings AM,Wiethe RW,Olepu S,Warner KR,Sarret P,Gendron L,Longpre JM,Zhang Y,Runyon SP,Gilmour BP

更新日期：2014-09-11 00:00:00

abstract：:EGFR-targeted inhibitors (gefitinib and erlotinib) provided an effective strategy for the treatment of non-small-cell lung cancer. However, the EGFR T790M secondary mutation has become a leading cause of clinically acquired resistance to these agents. Herein, on the basis of the previously reported irreversible EGFR i...

journal_title：Journal of medicinal chemistry

authors： Hao Y,Wang X,Zhang T,Sun D,Tong Y,Xu Y,Chen H,Tong L,Zhu L,Zhao Z,Chen Z,Ding J,Xie H,Xu Y,Li H

更新日期：2016-08-11 00:00:00

abstract：:4,4-Ditritio-(-)-nicotine (5) of high specific activity (4.7 Ci/mmol) has been synthesized from (-)-nicotine via the readily prepared 4,4-dibromocotinine (3). Scatchard analysis of the binding of 5 to the crude mitochondrial fraction of whole rat brain revealed a Ka of 4.7 X 10(6) M-1 and 13 fmol of binding sites/mg o...

journal_title：Journal of medicinal chemistry

authors： Vincek WC,Martin BR,Aceto MD,Bowman ER

更新日期：1980-08-01 00:00:00

abstract：:The crystal and molecular structure of metyrapone, a powerful inhibitor of certain cytochromes P-450, is described. Cytochrome P-450 enzymes are involved in metabolic processes, including those activating insecticides, drugs, and carcinogens. Metyrapone inhibits both the adrenal cytochrome P-450 catalyzing 11-beta-hyd...

journal_title：Journal of medicinal chemistry

authors： Rossi M

更新日期：1983-09-01 00:00:00

abstract：:The potencies of a series of 2 beta-substituted cocaine analogues to displace [3H]-3 beta-(p-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester binding in rat striatal membranes demonstrate the requirement for a 2 beta-substituent with two hydrogen-bond acceptors. The insensitivity of the ester moiety to steric ...

journal_title：Journal of medicinal chemistry

authors： Lewin AH,Gao YG,Abraham P,Boja JW,Kuhar MJ,Carroll FI

更新日期：1992-01-01 00:00:00