Synthesis and biological activity of C-terminally truncated fragments of human alpha-calcitonin gene-related peptide.

abstract：:3',5'-Diamino-3',5'-dideoxythymidine (7) was synthesized via a nine-step synthesis from thymidine in good overall yield. 3'-Amino-3'-deoxythymidine (8) and 5'-amino-5'-deoxythymidine (12) were prepared with a minor modification of the procedure reported by Horwitz and co-workers. Although the 5'-amino analogue 12 had ...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Prusoff WH

更新日期：1978-01-01 00:00:00

abstract：:A pair of enantiomeric Pt(II) complexes, [Pt(R-ahaz)Cl2] and [Pt(S-ahaz)Cl2] (ahaz = 3-aminohexahydroazepine), has been investigated for their ability to bind enantioselectively to DNA. Improved synthetic procedures were developed for preparing both the ligands and the Pt complexes. The structure of the complex of the...

journal_title：Journal of medicinal chemistry

authors： Fenton RR,Easdale WJ,Er HM,O'Mara SM,McKeage MJ,Russell PJ,Hambley TW

更新日期：1997-03-28 00:00:00

abstract：:The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors mu, kappa, delta), with 14-phenylpropoxym...

journal_title：Journal of medicinal chemistry

authors： Schütz J,Spetea M,Koch M,Aceto MD,Harris LS,Coop A,Schmidhammer H

更新日期：2003-09-11 00:00:00

abstract：:A series of novel compounds having a benzothiazoline skeleton was studied for their structure-activity relationship (SAR) with respect to Ca2+ antagonistic activity. As test compounds, analogues of 3-acyl-2-arylbenzothiazolines (3) were synthesized. Benzothiazoline derivatives (3) exerted higher Ca2+ antagonistic acti...

journal_title：Journal of medicinal chemistry

authors： Yamamoto K,Fujita M,Tabashi K,Kawashima Y,Kato E,Oya M,Iso T,Iwao J

更新日期：1988-05-01 00:00:00

abstract：:Reaction of nitric oxide (NO) with L-proline in methanolic sodium methoxide yields a diazeniumdiolate product, C5H7N3O4Na2.CH3OH (PROLI/NO), that can be stabilized in basic solution but that dissociates to proline (1 mol) and NO (2 mol) with a half-life of only 1.8 s at pH 7.4 and 37 degrees C. This kinetic behavior h...

journal_title：Journal of medicinal chemistry

authors： Saavedra JE,Southan GJ,Davies KM,Lundell A,Markou C,Hanson SR,Adrie C,Hurford WE,Zapol WM,Keefer LK

更新日期：1996-10-25 00:00:00

abstract：:A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha 2- and/or alpha 3- over alpha 1-containing GABA(A) receptor subtypes and high ...

journal_title：Journal of medicinal chemistry

authors： Collins I,Moyes C,Davey WB,Rowley M,Bromidge FA,Quirk K,Atack JR,McKernan RM,Thompson SA,Wafford K,Dawson GR,Pike A,Sohal B,Tsou NN,Ball RG,Castro JL

更新日期：2002-04-25 00:00:00

abstract：:We have discovered N-butyl-N'-[2-(dimethylamino)-6-[3-(4-phenyl-1H- imidazol-1-yl)propoxy]phenyl]urea (4), a novel, potent, and systemically bioavailable inhibitor of ACAT (acylCoA:cholesterol O-acyltransferase). The structure-activity relationships (SARs) of this lead compound 4 were investigated by systematic modifi...

journal_title：Journal of medicinal chemistry

authors： Kimura T,Takase Y,Hayashi K,Tanaka H,Ohtsuka I,Saeki T,Kogushi M,Yamada T,Fujimori T,Saitou I

更新日期：1993-05-28 00:00:00

abstract：:The synthetic pentasaccharide (1) corresponding to the heparin sequence which binds to, and activates, antithrombin III (AT III) is a potent antithrombotic compound in several animal models of venous thrombosis. We describe here the preparation and the pharmacological properties of 34, an analogue of oligosaccharide 1...

journal_title：Journal of medicinal chemistry

authors： Petitou M,Duchaussoy P,Jaurand G,Gourvenec F,Lederman I,Strassel JM,Bârzu T,Crépon B,Hérault JP,Lormeau JC,Bernat A,Herbert JM

更新日期：1997-05-23 00:00:00

abstract：:In the course of studies on tranquilizers, new non-benzodiazepine-like compounds were synthesized. These are 1-(3,4,5-trimethoxyphenoxy)-3-[4-(2-methoxyphenyl)piperazinyl]prop an-2-ol (INN: enciprazine) and derivatives thereof which were screened pharmacologically in order to evaluate their central nervous system acti...

journal_title：Journal of medicinal chemistry

authors： Engel J,Fleischhauer I,Jakovlev V,Kleemann A,Kutscher B,Nickel B,Rauer H,Werner U,Szelenyi I,Johanson CE

更新日期：1990-11-01 00:00:00

abstract：:The binding affinities at rat A1, A2a, and A3 adenosine receptors of a wide range of derivatives of adenosine have been determined. Sites of modification include the purine moiety (1-, 3-, and 7-deaza; halo, alkyne, and amino substitutions at the 2- and 8-positions; and N6-CH2-ring, -hydrazino, and -hydroxylamino) and...

journal_title：Journal of medicinal chemistry

authors： Siddiqi SM,Jacobson KA,Esker JL,Olah ME,Ji XD,Melman N,Tiwari KN,Secrist JA 3rd,Schneller SW,Cristalli G

更新日期：1995-03-31 00:00:00

abstract：:We report X-ray crystallographic structures of three inhibitors bound to dehydrosqualene synthase from Staphylococcus aureus: 1 (BPH-651), 2 (WC-9), and 3 (SQ-109). Compound 2 binds to the S2 site with its -SCN group surrounded by four hydrogen bond donors. With 1, we report two structures: in both, the quinuclidine h...

journal_title：Journal of medicinal chemistry

authors： Lin FY,Liu YL,Li K,Cao R,Zhu W,Axelson J,Pang R,Oldfield E

更新日期：2012-05-10 00:00:00

abstract：:Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, "uracil anhydride") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine...

journal_title：Journal of medicinal chemistry

authors： Chwang TL,Wood WF,Parkhurst JR,Nesnow S,Danenberg PV,Heidelberger C

更新日期：1976-05-01 00:00:00

abstract：:A series of potent nonpeptide inhibitors of the HIV protease have been identified. Using the structure of compound 3 bound to the HIV protease, bis tertiary amide inhibitor 9 was designed and prepared. Compound 9 was found to be about 17 times more potent than 3, and the structure of the protein-ligand complex of 9 re...

journal_title：Journal of medicinal chemistry

authors： Melnick M,Reich SH,Lewis KK,Mitchell LJ Jr,Nguyen D,Trippe AJ,Dawson H,Davies JF 2nd,Appelt K,Wu BW,Musick L,Gehlhaar DK,Webber S,Shetty B,Kosa M,Kahil D,Andrada D

更新日期：1996-07-05 00:00:00

abstract：:The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MR...

journal_title：Journal of medicinal chemistry

authors： Ma Z,Chu DT,Cooper CS,Li Q,Fung AK,Wang S,Shen LL,Flamm RK,Nilius AM,Alder JD,Meulbroek JA,Or YS

更新日期：1999-10-07 00:00:00

abstract：:The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1....

journal_title：Journal of medicinal chemistry

authors： Meng H,Krishnaji ST,Beinborn M,Kumar K

更新日期：2008-11-27 00:00:00

abstract：:Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) pos...

journal_title：Journal of medicinal chemistry

authors： Devraj R,Barrett JF,Fernandez JA,Katzenellenbogen JA,Cushman M

更新日期：1996-08-16 00:00:00

abstract：:The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational modification of lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acq...

journal_title：Journal of medicinal chemistry

authors： Kumari S,Carmona AV,Tiwari AK,Trippier PC

更新日期：2020-11-12 00:00:00

abstract：:In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation and biological activity of fourteen new and five known dihydro-beta-agarofuran sesquiterpenes from the leaves of Zinowiewia costaricensis (1-19). Their structures were determined by means of (1)H and (13)C N...

journal_title：Journal of medicinal chemistry

authors： Muñoz-Martínez F,Mendoza CR,Bazzocchi IL,Castanys S,Jiménez IA,Gamarro F

更新日期：2005-06-30 00:00:00

abstract：:The antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilin...

journal_title：Journal of medicinal chemistry

authors： Pletsas D,Garelnabi EA,Li L,Phillips RM,Wheelhouse RT

更新日期：2013-09-12 00:00:00

abstract：:Disubstituted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural evaluation. Structure-activity studies centered on the bicyclic beta-turn mimic contained in these molecules indicated that this moiety could accommodate a variety of modifications. Specifically, monocyclic, 6, ...

journal_title：Journal of medicinal chemistry

authors： Fisher MJ,Arfstan AE,Giese U,Gunn BP,Harms CS,Khau V,Kinnick MD,Lindstrom TD,Martinelli MJ,Mest HJ,Mohr M,Morin JM Jr,Mullaney JT,Nunes A,Paal M,Rapp A,Rühter G,Ruterbories KJ,Sall DJ,Scarborough RM,Schotten T,S

更新日期：1999-11-18 00:00:00

abstract：:Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimeth...

journal_title：Journal of medicinal chemistry

authors： da Silva EN Jr,de Deus CF,Cavalcanti BC,Pessoa C,Costa-Lotufo LV,Montenegro RC,de Moraes MO,Pinto Mdo C,de Simone CA,Ferreira VF,Goulart MO,Andrade CK,Pinto AV

更新日期：2010-01-14 00:00:00

abstract：:Cyclopropylcarboxylic acids and esters and cyclopropylmethanols incorporating bromophenol moieties were investigated as inhibitors of the carbonic anhydrase enzyme (CA; EC 4.2.1.1). The cis- and trans-esters 5 and 6 were obtained from the reaction of 4-allyl-1,2-dimethoxybenzene (4) with ethyl diazoacetate, which afte...

journal_title：Journal of medicinal chemistry

authors： Boztaş M,Çetinkaya Y,Topal M,Gülçin İ,Menzek A,Şahin E,Tanc M,Supuran CT

更新日期：2015-01-22 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：:The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII a...

journal_title：Journal of medicinal chemistry

authors： Wright WB Jr,Press JB,Chan PS,Marsico JW,Haug MF,Lucas J,Tauber J,Tomcufcik AS

更新日期：1986-04-01 00:00:00

abstract：:The inhibitory activity of 1058 inhibitors of the title enzymes has been formulated in 13 equations correlating chemical structure with inhibitory potency. Two types of regions in enzymes have been defined by means of pi and molar refractivity constants. The use of indicator variables has been extensively developed to...

journal_title：Journal of medicinal chemistry

authors： Yoshimoto M,Hansch C

更新日期：1976-01-01 00:00:00

abstract：:Three N-C8-bridged analogues 4-6 of the opiate etorphine (3) were synthesized and evaluated for opiate agonism and antagonism. In each case ring closure was effected by intramolecular N-alkylation with a suitably developed C8 side chain. Another key synthetic step was the selective monoprotection of diol 11, which all...

journal_title：Journal of medicinal chemistry

authors： Maurer PJ,Rapoport H

更新日期：1987-11-01 00:00:00

abstract：:As a continuation of our project aimed at the search for new and safe chemotherapeutic and chemoprophylactic agents against American trypanosomiasis (Chagas' disease), several drugs structurally related to 4-phenoxyphenoxyethyl thiocyanate (4) were designed, synthesized, and evaluated as antiproliferative agents again...

journal_title：Journal of medicinal chemistry

authors： Elhalem E,Bailey BN,Docampo R,Ujváry I,Szajnman SH,Rodriguez JB

更新日期：2002-08-29 00:00:00

abstract：:We report, for the first time, the biological activities of four-carbon-atom bridged classical antifolates on dihydrofolate reductase (DHFR), thymidylate synthase (TS), and folylpolyglutamate synthetase (FPGS) as well as antitumor activity. Extension of the bridge homologation studies of classical two-carbon bridged a...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Zeng Y,McGuire JJ,Kisliuk RL

更新日期：2005-08-11 00:00:00

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

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

abstract：:Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(na...

journal_title：Journal of medicinal chemistry

authors： Kokotos G,Hsu YH,Burke JE,Baskakis C,Kokotos CG,Magrioti V,Dennis EA

更新日期：2010-05-13 00:00:00