Derivatives of 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine as central nervous system agents.

abstract：:A series of amide analogues of the 2,2'-dithiobis(1H-indole-3-alkaonic acid) class of tyrosine kinase inhibitors have been prepared, by reaction of 1H-indole-3-alkanamides (8) with S2Cl2, and separation of the desired disulfides from the initial mixtures of mono-, di-, and trisulfides formed. These amides were evaluat...

journal_title：Journal of medicinal chemistry

authors： Thompson AM,Fry DW,Kraker AJ,Denny WA

更新日期：1994-03-04 00:00:00

abstract：:We report here the design, preparation, and systematic evaluation of a novel cycloalkane[d]isoxazole pharmacophoric fragment-containing androgen receptor (AR) modulators. Cycloalkane[d]isoxazoles form new core structures that interact with the hydrophobic region of the AR ligand-binding domain. To systematize and rati...

journal_title：Journal of medicinal chemistry

authors： Poutiainen PK,Oravilahti T,Peräkylä M,Palvimo JJ,Ihalainen JA,Laatikainen R,Pulkkinen JT

更新日期：2012-07-26 00:00:00

abstract：:We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitr...

journal_title：Journal of medicinal chemistry

authors： Rai D,Johar M,Manning T,Agrawal B,Kunimoto DY,Kumar R

更新日期：2005-11-03 00:00:00

abstract：:The simulated binding profiles of acetylcholine, ACh, and the inhibitor (+/-)-2,3-dihydro-5,6- dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-on e hydrochloride (E2020), 1, and some of its analogs to acetylcholinesterase, AChE, were determined using full force field energetics and allowing complete co...

journal_title：Journal of medicinal chemistry

authors： Inoue A,Kawai T,Wakita M,Iimura Y,Sugimoto H,Kawakami Y

更新日期：1996-10-25 00:00:00

abstract：:The ghrelin receptor displays a high constitutive activity suggested to be involved in the regulation of appetite and food intake. Here, we have created peptides with small changes in the core binding motif -wFw- of the hexapeptide KwFwLL-NH(2) that can swap the peptide behavior from inverse agonism to agonism, indica...

journal_title：Journal of medicinal chemistry

authors： Els S,Schild E,Petersen PS,Kilian TM,Mokrosinski J,Frimurer TM,Chollet C,Schwartz TW,Holst B,Beck-Sickinger AG

更新日期：2012-09-13 00:00:00

abstract：:This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determ...

journal_title：Journal of medicinal chemistry

authors： Giovagnini L,Ronconi L,Aldinucci D,Lorenzon D,Sitran S,Fregona D

更新日期：2005-03-10 00:00:00

abstract：:A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- ...

journal_title：Journal of medicinal chemistry

authors： Nishikawa Y,Shindo T,Ishii K,Nakamura H,Kon T,Uno H

更新日期：1989-03-01 00:00:00

abstract：:The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural p...

journal_title：Journal of medicinal chemistry

authors： Behnam MA,Graf D,Bartenschlager R,Zlotos DP,Klein CD

更新日期：2015-12-10 00:00:00

abstract：:We have focused on optimization of the inadequate pharmacokinetic profile of trans-4-substituted cyclohexanecarboxylic acid 5, which is commonly observed in many small molecule very late antigen-4 (VLA-4) antagonists. We modified the lipophilic moiety in 5 and found that reducing the polar surface area of this moiety ...

journal_title：Journal of medicinal chemistry

authors： Muro F,Iimura S,Sugimoto Y,Yoneda Y,Chiba J,Watanabe T,Setoguchi M,Iigou Y,Matsumoto K,Satoh A,Takayama G,Taira T,Yokoyama M,Takashi T,Nakayama A,Machinaga N

更新日期：2009-12-24 00:00:00

abstract：:UDP and UDP-glucose activate the P2Y14 receptor (P2Y14R) to modulate processes related to inflammation, diabetes, and asthma. A computational pipeline suggested alternatives to naphthalene of a previously reported P2Y14R antagonist (3, PPTN) using docking and molecular dynamics simulations on a hP2Y14R homology model ...

journal_title：Journal of medicinal chemistry

authors： Junker A,Balasubramanian R,Ciancetta A,Uliassi E,Kiselev E,Martiriggiano C,Trujillo K,Mtchedlidze G,Birdwell L,Brown KA,Harden TK,Jacobson KA

更新日期：2016-07-14 00:00:00

abstract：:Endothelin-converting enzyme-2 (ECE-2), a member of M13 family of zinc metallopeptidases, has previously been shown to process a number of neuropeptides including those derived from prodynorphin, proenkephalin, proSAAS, and amyloid precursor protein. ECE-2, unlike ECE-1, exhibits restricted neuroendocrine distribution...

journal_title：Journal of medicinal chemistry

authors： Gagnidze K,Sachchidanand,Rozenfeld R,Mezei M,Zhou MM,Devi LA

更新日期：2008-06-26 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：:Nitrogen mustards, widely used as chemotherapeutics, have limited safety and efficacy. Mitochondria lack a functional nucleotide excision repair mechanism to repair DNA adducts and are sensitive to alkylating agents. Importantly, cancer cells have higher intrinsic mitochondrial membrane potential (Δψmt) than normal ce...

journal_title：Journal of medicinal chemistry

authors： Millard M,Gallagher JD,Olenyuk BZ,Neamati N

更新日期：2013-11-27 00:00:00

abstract：:Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminometh...

journal_title：Journal of medicinal chemistry

authors： Kung HF,Newman S,Choi SR,Oya S,Hou C,Zhuang ZP,Acton PD,Plössl K,Winkler J,Kung MP

更新日期：2004-10-07 00:00:00

abstract：:The nortropane cocaine analogue, 2beta-carbomethoxy-3beta-[4'-((Z)-2-iodoethenyl)phenyl]nortropane (ZIENT), is a high affinity, selective serotonin transporter (SERT) ligand that has shown promise as a SERT imaging agent for single photon computed tomography (SPECT) when labeled with I-123. Synthesis of the labeling p...

journal_title：Journal of medicinal chemistry

authors： Plisson C,Jarkas N,McConathy J,Voll RJ,Votaw J,Williams L,Howell LL,Kilts CD,Goodman MM

更新日期：2006-02-09 00:00:00

abstract：:Probucol (1) and probucol analogues with the substitutions at the disulfide-linked carbon (2, 3) and an additional substitution at a tert-butyl of each phenolic ring (4) were tested for their ability to lower total serum cholesterol and prevent aortic atherosclerosis in modified Watanabe heritable hyperlipidemic (WHHL...

journal_title：Journal of medicinal chemistry

authors： Mao SJ,Yates MT,Rechtin AE,Jackson RL,Van Sickle WA

更新日期：1991-01-01 00:00:00

abstract：:1-Aroylindoline, 1-aroyl-1,2,3,4-tetrahydroquinoline, and 1-aroylindole derivatives were synthesized and evaluated for anticancer activity. The 4-amino and 4-hydroxy-1-aroylindoles 26 and 27 with IC 50 of 0.9 and 0.6 microM, respectively, exhibited antitubulin activity superior or comparable to that of colchicine and ...

journal_title：Journal of medicinal chemistry

authors： Liou JP,Wu ZY,Kuo CC,Chang CY,Lu PY,Chen CM,Hsieh HP,Chang JY

更新日期：2008-07-24 00:00:00

abstract：:The mixed topoisomerase I/II inhibitor N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is currently in clinical trial as an anticancer drug. A series of acridine-substituted analogues were prepared, using a new synthetic route to substituted acridine-4-carboxylic acids (conversion of substituted diphenylamine ...

journal_title：Journal of medicinal chemistry

authors： Spicer JA,Gamage SA,Atwell GJ,Finlay GJ,Baguley BC,Denny WA

更新日期：1997-06-06 00:00:00

abstract：:RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promi...

journal_title：Journal of medicinal chemistry

authors： Deng J,Feng E,Ma S,Zhang Y,Liu X,Li H,Huang H,Zhu J,Zhu W,Shen X,Miao L,Liu H,Jiang H,Li J

更新日期：2011-07-14 00:00:00

abstract：:Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the ...

journal_title：Journal of medicinal chemistry

authors： Devasthale P,Wang Y,Wang W,Fevig J,Feng J,Wang A,Harrity T,Egan D,Morgan N,Cap M,Fura A,Klei HE,Kish K,Weigelt C,Sun L,Levesque P,Moulin F,Li YX,Zahler R,Kirby MS,Hamann LG

更新日期：2013-09-26 00:00:00

abstract：:Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide an effective method for the treatment of proliferative diseases such as cancer. The pyrido[2,3-d]pyrimidin-7-one template has been identified previously as a privileged structure for the inhibition of ATP-dependent kinases, a...

journal_title：Journal of medicinal chemistry

authors： VanderWel SN,Harvey PJ,McNamara DJ,Repine JT,Keller PR,Quin J 3rd,Booth RJ,Elliott WL,Dobrusin EM,Fry DW,Toogood PL

更新日期：2005-04-07 00:00:00

abstract：:CXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis of cancer cells. We previously identified small molecule ligands that bind CXCL12 and block CXCR4-mediated chemotaxis. We now report a 1.9 Å resolution X-ray structure of CXCL12 bound by such a molecule at a site normally bound by sY21 of C...

journal_title：Journal of medicinal chemistry

authors： Smith EW,Liu Y,Getschman AE,Peterson FC,Ziarek JJ,Li R,Volkman BF,Chen Y

更新日期：2014-11-26 00:00:00

abstract：:A novel method for quantitative structure-activity relationship (QSAR) analysis is presented. The method, which does not assume any particular functional form for the QSAR, develops nonlinear relationships between parameters describing a set of molecules and the activity of the molecules. For the QSAR of the inhibitio...

journal_title：Journal of medicinal chemistry

authors： Hirst JD

更新日期：1996-08-30 00:00:00

abstract：:New and greatly improved preparations of the 12alpha,1'beta- (5) and 12beta,1'beta- (6) glucuronides of dihydroartemisinin (DHA, 2) are reported using anomeric hydroxy and imidate glucuronate intermediates. Comparison of the synthetic and natural materials shows that the human metabolite of DHA is the 12alpha-epimer 5...

journal_title：Journal of medicinal chemistry

authors： O'Neill PM,Scheinmann F,Stachulski AV,Maggs JL,Park BK

更新日期：2001-04-26 00:00:00

abstract：:Notch is a membrane inserted protein activated by the membrane-inserted γ-secretase proteolytic complex. The Notch pathway is a potential therapeutic target for the treatment of renal diseases but also controls the function of other cells, requiring cell-targeting of Notch antagonists. Toward selective targeting, we h...

journal_title：Journal of medicinal chemistry

authors： Juillerat-Jeanneret L,Flohr A,Schneider M,Walter I,Wyss JC,Kumar R,Golshayan D,Aebi JD

更新日期：2015-10-22 00:00:00

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

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

更新日期：2005-11-03 00:00:00

abstract：:1-[2-(Diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles (DAMNIs) is a novel family of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) active at submicromolar concentration. Replacement of one phenyl ring of 1-[2-(diphenylmethoxy)ethyl]-2-methyl-5-nitroimidazole (4) with heterocyclic rings, such as 2-thien...

journal_title：Journal of medicinal chemistry

authors： De Martino G,La Regina G,Di Pasquali A,Ragno R,Bergamini A,Ciaprini C,Sinistro A,Maga G,Crespan E,Artico M,Silvestri R

更新日期：2005-06-30 00:00:00

abstract：:A series of novel 2-substituted acetylenic pyrrolidines and piperidines related to oxotremorine (1) were prepared and evaluated in vitro as muscarinic cholinergic agents at brain M1 and M2 receptors. One analogue, 3-(2-oxo-1-pyrrolidinyl)-1-[2(R)-pyrrolidinyl]-1-propyne hydrogen oxalate (6a), was found to be a partial...

journal_title：Journal of medicinal chemistry

authors： Garvey DS,Wasicak JT,Chung JY,Shue YK,Carrera GM,May PD,McKinney MM,Anderson D,Cadman E,Vella-Rountree L

更新日期：1992-05-01 00:00:00

abstract：:The paullones represent a novel class of small molecule cyclin-dependent kinase (CDK) inhibitors. To investigate structure-activity relationships and to develop paullones with antitumor activity, derivatives of the lead structure kenpaullone (9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one, 4a) were synthesiz...

journal_title：Journal of medicinal chemistry

authors： Schultz C,Link A,Leost M,Zaharevitz DW,Gussio R,Sausville EA,Meijer L,Kunick C

更新日期：1999-07-29 00:00:00

abstract：:The mitotic spindle is a validated target for cancer chemotherapy. Drugs such as taxanes and vinca alkaloids specifically target microtubules and cause the mitotic spindle to collapse. However, toxicity and resistance are problems associated with these drugs. Thus, alternative approaches to inhibiting the mitotic spin...

journal_title：Journal of medicinal chemistry

authors： Kaan HY,Weiss J,Menger D,Ulaganathan V,Tkocz K,Laggner C,Popowycz F,Joseph B,Kozielski F

更新日期：2011-03-24 00:00:00