Novel 99mTc aminobisthiolato/monothiolato "3 + 1" mixed ligand complexes: structure-activity relationships and preliminary in vivo validation as brain blood flow imaging agents.

abstract：:The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and ...

journal_title：Journal of medicinal chemistry

authors： Raitio KH,Savinainen JR,Vepsäläinen J,Laitinen JT,Poso A,Järvinen T,Nevalainen T

更新日期：2006-03-23 00:00:00

abstract：:We previously reported (J. Med. Chem. 1993, 36, 1188-1193) that changes to the ring size of the piperidine and cyclohexyl rings of the high-affinity and selective dopamine (DA)-uptake inhibitor 1-[1-(2-benzo[b]thienyl)cyclohexyl]piperidine (BTCP, 2) caused different, and in some cases opposite, changes in affinity for...

journal_title：Journal of medicinal chemistry

authors： He X,Raymon LP,Mattson MV,Eldefrawi ME,de Costa BR

更新日期：1993-12-10 00:00:00

abstract：:The discovery of the (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted the investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were the subjects of this study. Those compounds, unlike the monocycli...

journal_title：Journal of medicinal chemistry

authors： Woltersdorf OW Jr,deSolms SJ,Schultz EM,Cragoe EJ Jr

更新日期：1977-11-01 00:00:00

abstract：:Protein arginine methyltransferase 1 (PRMT1) is involved in many biological activities, such as gene transcription, signal transduction, and RNA processing. Overexpression of PRMT1 is related to cardiovascular diseases, kidney diseases, and cancers; therefore, selective PRMT1 inhibitors serve as chemical probes to inv...

journal_title：Journal of medicinal chemistry

authors： Hu H,Owens EA,Su H,Yan L,Levitz A,Zhao X,Henary M,Zheng YG

更新日期：2015-02-12 00:00:00

abstract：:Homology modeling of G-protein-coupled seven-transmembrane receptors (GPCRs) remains a challenge despite the increasing number of released GPCR crystal structures. This challenge can be attributed to the low sequence identity and structural diversity of the ligand-binding pocket of GPCRs. We have developed an optimize...

journal_title：Journal of medicinal chemistry

authors： Yoshikawa Y,Oishi S,Kubo T,Tanahara N,Fujii N,Furuya T

更新日期：2013-06-13 00:00:00

abstract：:The syntheses of 2-amino-N-(2-benzoyl)-4-chlorophenyl)acetamides are reported. The pharmacological properties of these compounds were compared with data obtained from the corresponding cyclized products [5-(2,6-dichlorophenyl)-1,4-benzodiazepin-2-ones]. Evidence is presented which suggests that the central nervous sys...

journal_title：Journal of medicinal chemistry

authors： Fryer RI,Leimgruber W,Trybulski EJ

更新日期：1982-09-01 00:00:00

abstract：:The preparation and antitubercular properties of a series of 2,8-bis(alkylaminomethyl)phenazines are described. These compounds all inhibited the growth of Mycobacterium smegmatis ATCC 607 in vitro. 2,8-Bis(dibutylaminomethyl)phenazine (5c) was also active against a lethal Mycobacterium tuberculosis H37Rv infection in...

journal_title：Journal of medicinal chemistry

authors： Murdock KC,Lin Y,Thomas JP,Lang SA Jr

更新日期：1978-04-01 00:00:00

abstract：:Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of α4β2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techn...

journal_title：Journal of medicinal chemistry

authors： German N,Kim JS,Jain A,Dukat M,Pandya A,Ma Y,Weltzin M,Schulte MK,Glennon RA

更新日期：2011-10-27 00:00:00

abstract：:A series of analogues of the recently reported angiotensin II (AII) antagonist [Sar1]AII-(1-7)-amide or des-Phe8[Sar1]AII (3) have been prepared by solid-phase synthesis and purified by reverse-phase liquid chromatography. The agonist and antagonist properties of these carboxy-truncated analogues of AII were determine...

journal_title：Journal of medicinal chemistry

authors： Bovy PR,O'Neal JM,Olins GM,Patton DR,McMahon EG,Palomo M,Koepke JP,Salles KS,Trapani AJ,Smits GJ

更新日期：1990-05-01 00:00:00

abstract：:Network theory provides one of the most potent analysis tools for the study of complex systems. In this paper, we illustrate the network-based perspective in drug research and how it is coherent with the new paradigm of drug discovery. We first present data sources from which networks are built, then show some example...

journal_title：Journal of medicinal chemistry

authors： Recanatini M,Cabrelle C

更新日期：2020-08-27 00:00:00

abstract：:Novel dicationic triazoles 1-60 were synthesized by the Pinner method from the corresponding dinitriles, prepared via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The type and the placement of cationic moieties as well as the nature of aromatic substituents influenced in vitro antiprotozoal activities o...

journal_title：Journal of medicinal chemistry

authors： Bakunov SA,Bakunova SM,Wenzler T,Ghebru M,Werbovetz KA,Brun R,Tidwell RR

更新日期：2010-01-14 00:00:00

abstract：:Cdc7 serine/threonine kinase is a key regulator of DNA synthesis in eukaryotic organisms. Cdc7 inhibition through siRNA or prototype small molecules causes p53 independent apoptosis in tumor cells while reversibly arresting cell cycle progression in primary fibroblasts. This implies that Cdc7 kinase could be considere...

journal_title：Journal of medicinal chemistry

authors： Menichincheri M,Albanese C,Alli C,Ballinari D,Bargiotti A,Caldarelli M,Ciavolella A,Cirla A,Colombo M,Colotta F,Croci V,D'Alessio R,D'Anello M,Ermoli A,Fiorentini F,Forte B,Galvani A,Giordano P,Isacchi A,Martina K,

更新日期：2010-10-28 00:00:00

abstract：:Benzimidazoles carrying the 2-hydroxy-3-(isopropylamino)propoxy side chain at either the C-4 or C-5 ring positions were synthesized and investigated for beta-adrenergic blocking activity. Both compounds demonstrated beta2 selectivity when evaluated in guinea pig atrial and tracheal preparations. The C-4 isomer was 17 ...

journal_title：Journal of medicinal chemistry

authors： Crooks CR,Wright J,Callery PS,Moreton JE

更新日期：1979-02-01 00:00:00

abstract：:Recent studies have indicated several therapeutic applications for delta opioid agonists and antagonists. To exploit the therapeutic potential of delta opioids developing a structural basis for the activity of ligands at the delta opioid receptor is essential. The conformationally sampled pharmacophore (CSP) method (B...

journal_title：Journal of medicinal chemistry

authors： Bernard D,Coop A,MacKerell AD Jr

更新日期：2007-04-19 00:00:00

abstract：:A promising strategy for selecting synthetic targets is similarity-based searching of very large "virtual libraries", which comprise all structures accessible by linking two or three commercially available building blocks with combinatorial syntheses. To assess the general applicability of this strategy, leading struc...

journal_title：Journal of medicinal chemistry

authors： Andrews KM,Cramer RD

更新日期：2000-05-04 00:00:00

abstract：:A series of N,N-dialkyltryptamines with methylthio or methylenedioxy substituents in the 4, 5, and 6 positions and methyl or isopropyl on the side-chain nitrogen has been synthesized. The behavioral pharmacology of these compounds showed them to possess Bovet-Gatti profiles characteristic of hallucinogens, and the 5-m...

journal_title：Journal of medicinal chemistry

authors： Kline TB,Benington F,Morin RD,Beaton JM

更新日期：1982-08-01 00:00:00

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

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

abstract：:In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma w...

journal_title：Journal of medicinal chemistry

authors： Liu LQ,Hong PX,Song XH,Zhou CC,Ling R,Kang Y,Qi QR,Yang J

更新日期：2020-07-23 00:00:00

abstract：:Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial t...

journal_title：Journal of medicinal chemistry

authors： Duan F,Li X,Cai S,Xin G,Wang Y,Du D,He S,Huang B,Guo X,Zhao H,Zhang R,Ma L,Liu Y,Du Q,Wei Z,Xing Z,Liang Y,Wu X,Fan C,Ji C,Zeng D,Chen Q,He Y,Liu X,Huang W

更新日期：2014-05-08 00:00:00

abstract：:Autoimmune deficiency and destruction in either β-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A ...

journal_title：Journal of medicinal chemistry

authors： Liu YA,Jin Q,Zou Y,Ding Q,Yan S,Wang Z,Hao X,Nguyen B,Zhang X,Pan J,Mo T,Jacobsen K,Lam T,Wu TY,Petrassi HM,Bursulaya B,DiDonato M,Gordon WP,Liu B,Baaten J,Hill R,Nguyen-Tran V,Qiu M,Zhang YQ,Kamireddy A,

更新日期：2020-03-26 00:00:00

abstract：:The 5'-phosphate (1) of the antiviral nucleoside 5-cyano-2'-deoxyuridine was synthesized and evaluated for inhibition of thymidylate synthetase purified from methotrexate-resistant Lactobacillus casei. Compound 1 was a potent competitive inhibitor with a K1 of 0.55 microns. Irreversible enzyme inhibition by this compo...

journal_title：Journal of medicinal chemistry

authors： Chang CT,Edwards MW,Torrence PF,Mertes MP

更新日期：1979-09-01 00:00:00

abstract：:Treatment of a methanolic solution of 4-hydroxy-1-beta-D-ribofuranosyl-2-pyridinone (3-deazauridine, 1) with diazomethane gave 2-methoxy-1-beta-D-ribofuranosyl-4-pyridinone (2) and 4-methoxy-1-beta-D-ribofuranosyl-2-pyridinone (3a) in an approximate ratio of 1:2. Analogous treatment of 1 with diazomethane in the prese...

journal_title：Journal of medicinal chemistry

authors： Robins MJ,Lee AS

更新日期：1975-11-01 00:00:00

abstract：:P2Y(2) and P2Y(4) receptors are G protein-coupled receptors, activated by UTP and dinucleoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We structurally varied phosphate and uracil moieties in analogues of pyrimidine nucleoside 5'-triphosphates and ...

journal_title：Journal of medicinal chemistry

authors： Maruoka H,Jayasekara MP,Barrett MO,Franklin DA,de Castro S,Kim N,Costanzi S,Harden TK,Jacobson KA

更新日期：2011-06-23 00:00:00

abstract：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

journal_title：Journal of medicinal chemistry

authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

更新日期：2009-10-22 00:00:00

abstract：:The N-arginyl derivative of methionine-enkephalin (fragment 60-65 of beta-lipotropin) has been shown to be equiactive with the parent pentapeptide, despite the fact that the tyrosine amino group in this compound has been neutralized by the formation of an amide linkage. A series of N-(amino acid) derivatives of (-)-5,...

journal_title：Journal of medicinal chemistry

authors： Bélanger PC,Scheigetz J,Young RN,Charleson SE,Hudgin RL,Engelhardt EL

更新日期：1981-11-01 00:00:00

abstract：:The synthesis and in vitro antiplatelet activity significant data of coumarin derivatives 5i-x and quinolin-2(1H)-one derivatives 22a,b, as well as the corresponding structure-activity relationships are described. The recently reported 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin 5f and its potent 7-(2-morp...

journal_title：Journal of medicinal chemistry

authors： Roma G,Di Braccio M,Grossi G,Piras D,Leoncini G,Bruzzese D,Signorello MG,Fossa P,Mosti L

更新日期：2007-06-14 00:00:00

abstract：:Establishing quantitative relationships between molecular structure and broad biological effects has been a long-standing goal in drug discovery. Evaluation of the capacity of molecules to modulate protein functions is a prerequisite for understanding the relationship between molecular structure and in vivo biological...

journal_title：Journal of medicinal chemistry

authors： Fliri AF,Loging WT,Thadeio PF,Volkmann RA

更新日期：2005-11-03 00:00:00

abstract：:Multiple recent studies have focused on unraveling the content of the medicinal chemist's toolbox. Here, we present an investigation of chemical reactions and molecules retrieved from U.S. patents over the past 40 years (1976-2015). We used a sophisticated text-mining pipeline to extract 1.15 million unique whole reac...

journal_title：Journal of medicinal chemistry

authors： Schneider N,Lowe DM,Sayle RA,Tarselli MA,Landrum GA

更新日期：2016-05-12 00:00:00

abstract：:Two compounds, analogues of cephalexin with 2- and 4-pyridone groups at C-3, were prepared. Biological evaluation found the compounds to exhibit activity against Gram-positive and Gram-negative organisms in vitro and in vivo. The compounds were only active in vivo on subcutaneous administration. ...

journal_title：Journal of medicinal chemistry

authors： Edwards ML,Erickson RC

更新日期：1979-11-01 00:00:00

abstract：:Ac-Tyr298-Ala299-Gly300-Thr301-Val302-I le303-Asn304-Asp305-Leu306-OH (Ac-VZV R2-(298-306)) represents the acetylated form of the C-terminus of varicella-zoster virus (VZV) ribonucleotide reductase subunit 2 (R2). This peptide possesses a high degree of homology with the C-terminus nonapeptide of the herpes simplex vi...

journal_title：Journal of medicinal chemistry

authors： Gaudreau P,Brazeau P,Richer M,Cormier J,Langlois D,Langelier Y

更新日期：1992-01-24 00:00:00