Phosphorus-nitrogen compounds. 26. Phosphaminimides. 2. 2,2'-Phosphinylidenebis(1,1,1-trimethylhydrazinium) iodide inner salts as agents affecting ganglionic transmission.

abstract：:(R)-PCEP (3-amino-3-carboxypropyl-2'-carboxyethyl phosphinic acid, 1), a new metabotropic glutamate receptor 4 (mGlu4R) agonist, was discovered in a previously reported virtual screening. The (S)-enantiomer and a series of derivatives were synthesized and tested on recombinant mGlu4 receptors. A large number of deriva...

journal_title：Journal of medicinal chemistry

authors： Selvam C,Oueslati N,Lemasson IA,Brabet I,Rigault D,Courtiol T,Cesarini S,Triballeau N,Bertrand HO,Goudet C,Pin JP,Acher FC

更新日期：2010-04-08 00:00:00

abstract：:Inhibition of histone deacetylases (HDACs) leads to growth arrest, differentiation, or apoptosis of tumor cell lines, suggesting HDACs as promising targets for cancer therapy. At present, only one HDAC inhibitor (HDACi) is used in therapy: suberoylanilide hydroxamic acid (SAHA). Here, we describe the synthesis and bio...

journal_title：Journal of medicinal chemistry

authors： Oger F,Lecorgne A,Sala E,Nardese V,Demay F,Chevance S,Desravines DC,Aleksandrova N,Le Guével R,Lorenzi S,Beccari AR,Barath P,Hart DJ,Bondon A,Carettoni D,Simonneaux G,Salbert G

更新日期：2010-03-11 00:00:00

abstract：:A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-positi...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Du W,Hwang I,Rayl TJ,Kimball FS,Leung D,Hoover HS,Apodaca RL,Breitenbucher JG,Cravatt BF,Boger DL

更新日期：2007-03-08 00:00:00

abstract：:Adenosine induces glioma cell proliferation by means of an antiapoptotic effect, which is blocked by cotreatment with selective A(3) AR antagonists. In this study, a novel series of N(2)-substituted pyrazolo[3,4-d]pyrimidines 2a-u was developed as highly potent and selective A(3) AR antagonists. The most performing co...

journal_title：Journal of medicinal chemistry

authors： Taliani S,La Motta C,Mugnaini L,Simorini F,Salerno S,Marini AM,Da Settimo F,Cosconati S,Cosimelli B,Greco G,Limongelli V,Marinelli L,Novellino E,Ciampi O,Daniele S,Trincavelli ML,Martini C

更新日期：2010-05-27 00:00:00

abstract：:Using easily accessible keto-trioxanes 7a-g as the starting materials, a series of new variously functionalized 1,2,4-trioxanes 10-36 have been prepared and evaluated for antimalarial activity against multi-drug-resistant Plasmodium yoelii nigeriensis in mice in the dose range of 24 mg/kg x 4 days to 96 mg/kg x 4 days...

journal_title：Journal of medicinal chemistry

authors： Singh C,Malik H,Puri SK

更新日期：2006-05-04 00:00:00

abstract：:There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo ...

journal_title：Journal of medicinal chemistry

authors： Schenkel LB,Olivieri PR,Boezio AA,Deak HL,Emkey R,Graceffa RF,Gunaydin H,Guzman-Perez A,Lee JH,Teffera Y,Wang W,Youngblood BD,Yu VL,Zhang M,Gavva NR,Lehto SG,Geuns-Meyer S

更新日期：2016-03-24 00:00:00

abstract：:Generally, antipsychotic agents are dopamine receptor blocking agents that also block conditioned avoidance responding (CAR) in the rat. Recently, however, both (Q-methoxyphenyl)piperazine (OMPP, 1h) and (m-chlorophenyl)piperazine (MCPP, 1o) have been reported to block conditioned avoidance responding in the rat altho...

journal_title：Journal of medicinal chemistry

authors： Martin GE,Elgin RJ Jr,Mathiasen JR,Davis CB,Kesslick JM,Baldy WJ,Shank RP,DiStefano DL,Fedde CL,Scott MK

更新日期：1989-05-01 00:00:00

abstract：:The synthesis and sigma 1 and sigma 2 binding properties of several (+)- and (-)-2-benzyl- and 2-dimethylallyl-2'-substituted-5,9 alpha-dimethyl-6,7-benzomorphans (3 and 4) are presented. In agreement with previously reported binding data for 2-substituted 5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans (N-substituted...

journal_title：Journal of medicinal chemistry

authors： Danso-Danquah R,Bai X,Zhang X,Mascarella SW,Williams W,Sine B,Bowen WD,Carroll FI

更新日期：1995-07-21 00:00:00

abstract：:Two-bivalent ligands (P-X-P) containing the beta-naltrexamine pharmacophore (P) and a connecting oligoethylene glycol spanner (X) were synthesized and evaluated for narcotic antagonistic activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD). The bivalent ligand 2 whose spanner contains three ethylene uni...

journal_title：Journal of medicinal chemistry

authors： Erez M,Takemori AE,Portoghese PS

更新日期：1982-07-01 00:00:00

abstract：:Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC(50) values of the active compounds were in the range of 2-50 microM. Structure-activity relationship on the benzanilide moie...

journal_title：Journal of medicinal chemistry

authors： Suzuki T,Ando T,Tsuchiya K,Fukazawa N,Saito A,Mariko Y,Yamashita T,Nakanishi O

更新日期：1999-07-29 00:00:00

abstract：:Toward developing new potential analgesics, this first structure-activity relationship study of opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH), a human peptide inhibiting enkephalin degradation, was performed. A systematic Ala scanning proved that Phe(3) is a key residue for neprilysin and aminopeptidase N (AP-N) ectoenkephalin...

journal_title：Journal of medicinal chemistry

authors： Rosa M,Arsequell G,Rougeot C,Calle LP,Marcelo F,Pinto M,Centeno NB,Jiménez-Barbero J,Valencia G

更新日期：2012-02-09 00:00:00

abstract：:The synthesis of 5-(arylacetyl)-4-[(alkylamino)methyl]furo[3,2-c] pyridines (16-23, 26, 27) and their activities as kappa-opioid receptor agonists are described. kappa-Agonist potency was particularly sensitive to the nature of the basic moiety. In particular, in the rabbit vas deferens (kappa-specific tissue), the 3-...

journal_title：Journal of medicinal chemistry

authors： Naylor A,Judd DB,Scopes DI,Hayes AG,Birch PJ

更新日期：1994-07-08 00:00:00

abstract：:Antibiotic resistance represents a worldwide concern, especially regarding the outbreak of methicillin-resistant Staphylococcus aureus, a common cause for serious skin and soft tissues infections. A major contributor to Staphylococcus aureus antibiotic resistance is the NorA efflux pump, which is able to extrude selec...

journal_title：Journal of medicinal chemistry

authors： Lepri S,Buonerba F,Goracci L,Velilla I,Ruzziconi R,Schindler BD,Seo SM,Kaatz GW,Cruciani G

更新日期：2016-02-11 00:00:00

abstract：:Quantitative structure-activity relationship studies have been performed on two types of sulfonamides with hypoglycemic activity. In the case of the 2-benzenesulfonamidopyrimidines, substituted in the 5 position of the pyrimidine ring a correlation between hydrophobic forces, expressed as Rm values, and the binding to...

journal_title：Journal of medicinal chemistry

authors： Seydel JK,Ahrens H,Losert W

更新日期：1975-03-01 00:00:00

abstract：:In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane prepar...

journal_title：Journal of medicinal chemistry

authors： Chumpradit S,Kung MP,Panyachotipun C,Prapansiri V,Foulon C,Brooks BP,Szabo SA,Tejani-Butt S,Frazer A,Kung HF

更新日期：1992-11-13 00:00:00

abstract：:We have previously shown that the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA, 2), binds to AMPA receptors in a manner different from that of AMPA (1) itself and that 2, in contrast to 1, also binds to kainic acid re...

journal_title：Journal of medicinal chemistry

authors： Bang-Andersen B,Ahmadian H,Lenz SM,Stensbøl TB,Madsen U,Bøgesø KP,Krogsgaard-Larsen P

更新日期：2000-12-14 00:00:00

abstract：:(N)-Methanocarba adenosine 5'-methyluronamides containing known A(3) AR (adenosine receptor)-enhancing modifications, i.e., 2-(arylethynyl)adenine and N(6)-methyl or N(6)-(3-substituted-benzyl), were nanomolar full agonists of human (h) A(3)AR and highly selective (K(i) ∼0.6 nM, N(6)-methyl 2-(halophenylethynyl) analo...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Deflorian F,Phan K,Gao ZG,Wan TC,Gizewski E,Auchampach JA,Jacobson KA

更新日期：2012-05-24 00:00:00

abstract：:We have synthesized a series of N-phenyl-N'-aralkyl and N-phenyl-N'-(1-phenylcycloalkyl)ureas as inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). This intracellular enzyme is thought to be responsible for the esterification of dietary cholesterol; hence inhibition of this enzyme could reduce diet-induced hyp...

journal_title：Journal of medicinal chemistry

authors： Trivedi BK,Holmes A,Stoeber TL,Blankley CJ,Roark WH,Picard JA,Shaw MK,Essenburg AD,Stanfield RL,Krause BR

更新日期：1993-10-29 00:00:00

abstract：:Small molecule inhibitors of PARP-1 have been pursued by various organizations as potential therapeutic agents either capable of sensitizing cytotoxic treatments or acting as stand-alone agents to combat cancer. As one of the strategies to expand our portfolio of PARP-1 inhibitors, we pursued unsaturated heterocycles ...

journal_title：Journal of medicinal chemistry

authors： Tong Y,Bouska JJ,Ellis PA,Johnson EF,Leverson J,Liu X,Marcotte PA,Olson AM,Osterling DJ,Przytulinska M,Rodriguez LE,Shi Y,Soni N,Stavropoulos J,Thomas S,Donawho CK,Frost DJ,Luo Y,Giranda VL,Penning TD

更新日期：2009-11-12 00:00:00

abstract：:A series of modifications of the CCK7 analogue (des-NH2)Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2 was prepared and tested for binding to guinea pig CCK-A and CCK-B receptors and in CCK-A-mediated functional assays. Selected analogues also were tested for appetite suppressant activity in rats. Several conformationally rest...

journal_title：Journal of medicinal chemistry

authors： Holladay MW,Bennett MJ,Tufano MD,Lin CW,Asin KE,Witte DG,Miller TR,Bianchi BR,Nikkel AL,Bednarz L

更新日期：1992-08-07 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：: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：:Aberrant RET kinase signaling plays critical roles in several human cancers such as thyroid carcinoma. The gatekeeper mutants (V804L or V804M) of RET are resistant to currently approved RET inhibitors such as cabozantinib and vandetanib. We, for the first time, report a highly selective and extremely potent RET inhibi...

journal_title：Journal of medicinal chemistry

authors： Yoon H,Kwak Y,Choi S,Cho H,Kim ND,Sim T

更新日期：2016-01-14 00:00:00

abstract：:Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA(4)H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA(4)H. Lig...

journal_title：Journal of medicinal chemistry

authors： Sandanayaka V,Mamat B,Mishra RK,Winger J,Krohn M,Zhou LM,Keyvan M,Enache L,Sullins D,Onua E,Zhang J,Halldorsdottir G,Sigthorsdottir H,Thorlaksdottir A,Sigthorsson G,Thorsteinnsdottir M,Davies DR,Stewart LJ,Zembower DE

更新日期：2010-01-28 00:00:00

abstract：:The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly...

journal_title：Journal of medicinal chemistry

authors： Quiñones-Torrelo C,Sagrado S,Villanueva-Camañas RM,Medina-Hernández MJ

更新日期：1999-08-12 00:00:00

abstract：:Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) characterized by liver steatosis, inflammation, and hepatocellular damage. NASH is a serious condition that can progress to cirrhosis, liver failure, and hepatocellular carcinoma. The association of NASH with obesity, type...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Jones CT,Xu Y,Fenaux M,Halcomb RL

更新日期：2020-05-28 00:00:00

abstract：:A new paradigm for drug research has emerged, namely the deliberate search for molecules able to selectively affect the proliferation, differentiation, and migration of adult stem cells within the tissues in which they exist. Recently, there has been significant interest in medicinal chemistry toward the discovery and...

journal_title：Journal of medicinal chemistry

authors： Davies SG,Kennewell PD,Russell AJ,Seden PT,Westwood R,Wynne GM

更新日期：2015-04-09 00:00:00

abstract：:We have previously described a cyclic tetrapeptide, 1, that displays μ opioid receptor (MOPr) agonist and δ opioid receptor (DOPr) antagonist activity, a profile associated with a reduced incidence of opioid tolerance and dependence. Like many peptides, 1 has poor bioavailability. We describe here an analogue of 1 wit...

journal_title：Journal of medicinal chemistry

authors： Mosberg HI,Yeomans L,Anand JP,Porter V,Sobczyk-Kojiro K,Traynor JR,Jutkiewicz EM

更新日期：2014-04-10 00:00:00

abstract：:Dual target inhibitors against COX-2 and LTA(4)H were designed by adding functional groups from a marketed COX-2 inhibitor, Nimesulide, to an existing LTA(4)H inhibitor 1-(2-(4-phenoxyphenoxy) ethyl) pyrrolidine. A series of phenoxyphenyl pyrrolidine compounds were synthesized and tested for their inhibition activitie...

journal_title：Journal of medicinal chemistry

authors： Chen Z,Wu Y,Liu Y,Yang S,Chen Y,Lai L

更新日期：2011-05-26 00:00:00

abstract：:The IAPs are key regulators of the apoptotic pathways and are commonly overexpressed in many cancer cells. IAPs contain one to three BIR domains that are crucial for their inhibitory function. The pro-survival properties of XIAP come from binding of the BIR domains to the pro-apoptotic caspases. The BIR3 domain of XIA...

journal_title：Journal of medicinal chemistry

authors： Kester RF,Donnell AF,Lou Y,Remiszewski SW,Lombardo LJ,Chen S,Le NT,Lo J,Moliterni JA,Han X,Hogg JH,Liang W,Michoud C,Rupert KC,Mischke S,Le K,Weisel M,Janson CA,Lukacs CM,Fretland AJ,Hong K,Polonskaia A,Gao L

更新日期：2013-10-24 00:00:00