Synthesis of new linear guanidines and macrocyclic amidinourea derivatives endowed with high antifungal activity against Candida spp. and Aspergillus spp.

abstract：:To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of t...

journal_title：Journal of medicinal chemistry

authors： Suzuki T,Nagano Y,Kouketsu A,Matsuura A,Maruyama S,Kurotaki M,Nakagawa H,Miyata N

更新日期：2005-02-24 00:00:00

abstract：:In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...

journal_title：Journal of medicinal chemistry

authors： Clark RL,Pessolano AA,Shen TY,Jacobus DP,Jones H,Lotti VJ,Flataker LM

更新日期：1978-09-01 00:00:00

abstract：:In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in th...

journal_title：Journal of medicinal chemistry

authors： Ritter K,Buning C,Halland N,Pöverlein C,Schwink L

更新日期：2016-04-28 00:00:00

abstract：:Previously, vibsanin B (ViB) was found to preferentially target HSP90β compared to HSP90α. In this study, multiple experiments, including pull-down assays of biotin-ViB with recombinant HSP90β-NTD, MD, CTD, and full-length HSP90β, molecular docking of ViB and its derivatives to the HSP90 CTD, and a inhibition assay of...

journal_title：Journal of medicinal chemistry

authors： Shao LD,Su J,Ye B,Liu JX,Zuo ZL,Li Y,Wang YY,Xia C,Zhao QS

更新日期：2017-11-09 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：:Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent a...

journal_title：Journal of medicinal chemistry

authors： Temple C Jr,Rener GA,Waud WR,Noker PE

更新日期：1992-10-02 00:00:00

abstract：:Current drugs for the treatment of seizure disorders, although effective in many patients, still suffer from a number of failures and are not effective in some forms of resistant epilepsies. Historically, many of these drugs have multiple mechanisms of action including calcium and sodium channel blockade as well as GA...

journal_title：Journal of medicinal chemistry

authors： Fritch PC,McNaughton-Smith G,Amato GS,Burns JF,Eargle CW,Roeloffs R,Harrison W,Jones L,Wickenden AD

更新日期：2010-01-28 00:00:00

abstract：:4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives such as KN1022 are potent inhibitors of the phosphorylation of platelet derived growth factor receptor (PDGFR). Structure activity relationships in the (thio)urea moiety, the phenyl ring itself, the linker between these two moieti...

journal_title：Journal of medicinal chemistry

authors： Matsuno K,Nakajima T,Ichimura M,Giese NA,Yu JC,Lokker NA,Ushiki J,Ide S,Oda S,Nomoto Y

更新日期：2002-09-26 00:00:00

abstract：:The DNA-intercalating agent amsacrine is an effective drug for the treatment of human leukemias and lymphomas but has minimal solid tumor activity. As a first step in identifying analogues with a wider spectrum of activity, a comparison was made of the in vivo antileukemic (P-388) activity of amsacrine analogues given...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Atwell GJ,Baguley BC

更新日期：1984-03-01 00:00:00

abstract：:In order to expand the structure-activity relationship of tetramic acid molecules with structural similarity to the antibiotic reutericyclin, 22 compounds were synthesized and tested against a panel of clinically relevant bacteria. Key structural changes on the tetramic acid core affected antibacterial activity. Vario...

journal_title：Journal of medicinal chemistry

authors： Yendapally R,Hurdle JG,Carson EI,Lee RB,Lee RE

更新日期：2008-03-13 00:00:00

abstract：:A broad screening program previously identified phenprocoumon (1) as a small molecule template for inhibition of HIV protease. Subsequent modification of this lead through iterative cycles of structure-based design led to the activity enhancements of pyrone and dihydropyrone ring systems (II and V) and amide-based sub...

journal_title：Journal of medicinal chemistry

authors： Turner SR,Strohbach JW,Tommasi RA,Aristoff PA,Johnson PD,Skulnick HI,Dolak LA,Seest EP,Tomich PK,Bohanon MJ,Horng MM,Lynn JC,Chong KT,Hinshaw RR,Watenpaugh KD,Janakiraman MN,Thaisrivongs S

更新日期：1998-08-27 00:00:00

abstract：:Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycin...

journal_title：Journal of medicinal chemistry

authors： Elomri A,Mitaku S,Michel S,Skaltsounis AL,Tillequin F,Koch M,Pierré A,Guilbaud N,Léonce S,Kraus-Berthier L,Rolland Y,Atassi G

更新日期：1996-11-22 00:00:00

abstract：:1,2-Dihydro-1-(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e]in dole (CFI) as a novel replacement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of CC-1065, U-71184, and U-73975 (adozelesin) has been synthesized and incorporated into a series of efficacious antineoplastic agents. A partial solution to a...

journal_title：Journal of medicinal chemistry

authors： Mohamadi F,Spees MM,Staten GS,Marder P,Kipka JK,Johnson DA,Boger DL,Zarrinmayeh H

更新日期：1994-01-21 00:00:00

abstract：:Caveolin-1 is a target for academic and pharmaceutical research due to its many cellular roles and associated diseases. We report peptide WL47 (1), a small, high-affinity, selective disrupter of caveolin-1 oligomers. Developed and optimized through screening and analysis of synthetic peptide libraries, ligand 1 has 75...

journal_title：Journal of medicinal chemistry

authors： Gilliam AJ,Smith JN,Flather D,Johnston KM,Gansmiller AM,Fishman DA,Edgar JM,Balk M,Majumdar S,Weiss GA

更新日期：2016-04-28 00:00:00

abstract：:We recently discovered the isoform selective RAR beta 2 ligand 4'-octyl-4-biphenylcarboxylic acid (3, AC-55649). Although 3 is highly potent at RAR beta 2 and displays excellent selectivity, solubility issues make it unsuitable for drug development. Herein we describe the exploration of the SAR in a biphenyl and a phe...

journal_title：Journal of medicinal chemistry

authors： Lund BW,Knapp AE,Piu F,Gauthier NK,Begtrup M,Hacksell U,Olsson R

更新日期：2009-03-26 00:00:00

abstract：:Pironetin, the only crystallographically confirmed natural product to target α-tubulin, displays potent cytotoxic activity against sensitive and resistant A2780 ovarian cancer cell lines but is only marginally active in vivo. We now report that pironetin has a short half-life (<7 min) in human liver microsomes, sugges...

journal_title：Journal of medicinal chemistry

authors： Coulup SK,Huang DS,Wong HL,Georg GI

更新日期：2019-02-14 00:00:00

abstract：:All three amino-substituted 3-beta-D-ribofuranosyl-1,2,4-triazolo[4,3-b]pyridazines (5, 19, and 20) structurally related to formycin A were prepared and tested for their antitumor and antiviral activity in cell culture. Dehydrative coupling of 4-amino-5-chloro-3-hydrazinopyridazine (7) with 3,4,6-tri-O-benzoyl-2,5-anh...

journal_title：Journal of medicinal chemistry

authors： Kang Y,Larson SB,Robins RK,Revankar GR

更新日期：1989-07-01 00:00:00

abstract：:We have previously reported that compounds dimethyl-substituted on the phenyl ring of N-n-propyl-3-phenylpiperidines (PPEs) have a high (nM) affinity and selectivity toward the D(4) dopamine receptor (D(4) DAR) with m,p-dimethyl PPE (1) having the highest affinity and selectivity. In the present paper we have investig...

journal_title：Journal of medicinal chemistry

authors： Macchia M,Cervetto L,Demontis GC,Longoni B,Minutolo F,Orlandini E,Ortore G,Papi C,Sbrana A,Macchia B

更新日期：2003-01-02 00:00:00

abstract：:For a fourth approach of quinoxaline N,N'-dioxides as anti-trypanosomatid agents against T. cruzi and Leishmania, we found extremely active derivatives. The present study allows us to state the correct requirements for obtaining optimal in vitro anti-T. cruzi activity. Derivatives possessing electron-withdrawing subst...

journal_title：Journal of medicinal chemistry

authors： Benitez D,Cabrera M,Hernández P,Boiani L,Lavaggi ML,Di Maio R,Yaluff G,Serna E,Torres S,Ferreira ME,Vera de Bilbao N,Torres E,Pérez-Silanes S,Solano B,Moreno E,Aldana I,López de Ceráin A,Cerecetto H,González M,Monge

更新日期：2011-05-26 00:00:00

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

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

abstract：:Twelve 1,4-naphthoquinones have been tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis shows that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials. Although the toxicities of the compounds...

journal_title：Journal of medicinal chemistry

authors： Hodnett EM,Wongwiechintana C,Dunn WJ 3rd,Marrs P

更新日期：1983-04-01 00:00:00

abstract：:The synthesis of water-soluble, unsymmetrical, trisulfonated zinc phthalocyanines (ZnPcS3) as single products of the ring expansion of boron tri(4-sulfo)subphthalocyanine (SubPc) is reported. The novel, water-soluble trisulfo-SubPcB(OH) was prepared via hydrolysis of the tris(4-chlorosulfonyl)SubPcB(Br) which in turn ...

journal_title：Journal of medicinal chemistry

authors： Kudrevich S,Brasseur N,La Madeleine C,Gilbert S,van Lier JE

更新日期：1997-11-21 00:00:00

abstract：:Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluate...

journal_title：Journal of medicinal chemistry

authors： Haadsma-Svensson SR,Svensson K,Duncan N,Smith MW,Lin CH

更新日期：1995-02-17 00:00:00

abstract：:Fragment optimizations in nearly 150 fragment-based drug discovery programs reported in the literature during the past fifteen years were investigated. By analyzing physicochemical properties and ligand efficiency indices we found that biochemical detection methods yield hits with superior ligand efficiency and lipoph...

journal_title：Journal of medicinal chemistry

authors： Ferenczy GG,Keserű GM

更新日期：2013-03-28 00:00:00

abstract：:Human immunodeficiency virus type 1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Therefore, IN inhibitors are being sought for chemotherapy against AIDS. We had previously identified a series of salicylhydrazides as potent inhibitors of IN in vitro (Neamati, N.; et al. J. Med. Chem. 199...

journal_title：Journal of medicinal chemistry

authors： Neamati N,Lin Z,Karki RG,Orr A,Cowansage K,Strumberg D,Pais GC,Voigt JH,Nicklaus MC,Winslow HE,Zhao H,Turpin JA,Yi J,Skalka AM,Burke TR Jr,Pommier Y

更新日期：2002-12-19 00:00:00

abstract：:Molecular docking studies of carbohydrate derivatives in protein binding sites are often challenging because of water-mediated interactions and the inherent flexibility of the many terminal hydroxyl groups. Using the recognition process between heat-labile enterotoxin from Escherichia coli and ganglioside GM1 as a par...

journal_title：Journal of medicinal chemistry

authors： Minke WE,Diller DJ,Hol WG,Verlinde CL

更新日期：1999-05-20 00:00:00

abstract：:Quadruplex-forming sequences are widely prevalent in human and other genomes, including bacterial ones. These sequences are over-represented in eukaryotic telomeres, promoters, and 5' untranslated regions. They can form quadruplex structures, which may be transient in many situations in normal cells since they can be ...

journal_title：Journal of medicinal chemistry

authors： Neidle S

更新日期：2016-07-14 00:00:00

abstract：:Interaction of 2-iodoaniline or 5-fluoro-2-iodoaniline with a range of arylsulfonyl chlorides affords sulfonamides that undergo Sonogashira couplings under thermal or microwave conditions with the alkyne 4-ethynyl-4-hydroxycyclohexa-2,5-dien-1-one followed by cyclization to 4-[1-(arylsulfonyl-1H-indol-2-yl)]-4-hydroxy...

journal_title：Journal of medicinal chemistry

authors： McCarroll AJ,Bradshaw TD,Westwell AD,Matthews CS,Stevens MF

更新日期：2007-04-05 00:00:00

abstract：:A method for preparing a variety of 7-alkyl-6,7- didehydromorphinans from the corresponding 6- morphinanones is described. The key intermediates in this sequence are the 7-formyl derivatives. The two epimeric B/C-trans-7-(1- hydroxypentyl ) morphinans ( 16a ,b) are stereochemically similar to the endo- ethanotetrahydr...

journal_title：Journal of medicinal chemistry

authors： Quick J,Herlihy P,Howes JF

更新日期：1984-05-01 00:00:00

abstract：:A series of imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas containing substituted phenyl groups at the 3-position was developed. Compounds within the imidazo[1,5-alpha]quinoxaline urea series had high affinity for the GABAA/benzodiazepine receptor complex with varying in vitro efficacy, al...

journal_title：Journal of medicinal chemistry

authors： Jacobsen EJ,Stelzer LS,Belonga KL,Carter DB,Im WB,Sethy VH,Tang AH,VonVoigtlander PF,Petke JD

更新日期：1996-09-13 00:00:00