Pyrrolopyrazinedione-based inhibitors of human hormone-sensitive lipase.

abstract：:We report the discovery of chroman 28, a potent and selective antagonist of human, nonhuman primate, rat, and rabbit bradykinin B1 receptors (0.4-17 nM). At 90 mg/kg s.c., 28 decreased plasma extravasation in two rodent models of inflammation. A novel method to calculate entropy is introduced and ascribed approximatel...

journal_title：Journal of medicinal chemistry

authors： D'Amico DC,Aya T,Human J,Fotsch C,Chen JJ,Biswas K,Riahi B,Norman MH,Willoughby CA,Hungate R,Reider PJ,Biddlecome G,Lester-Zeiner D,Staden CV,Johnson E,Kamassah A,Arik L,Wang J,Viswanadhan VN,Groneberg RD,Zhan J,

更新日期：2007-02-22 00:00:00

abstract：:Glucuronidation and transporter-mediated efflux into bile are important in the elimination of xeno- and endobiotics, including the natural biladienone pigment bilirubin. The mechanisms of these processes and the structural factors that dictate whether cholephilic compounds are excreted directly in bile or require prio...

journal_title：Journal of medicinal chemistry

authors： McDonagh AF,Lightner DA

更新日期：2007-02-08 00:00:00

abstract：:A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cycli...

journal_title：Journal of medicinal chemistry

authors： Kim HS,Shibata Y,Wataya Y,Tsuchiya K,Masuyama A,Nojima M

更新日期：1999-07-15 00:00:00

abstract：:A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2-125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the co...

journal_title：Journal of medicinal chemistry

authors： Depreux P,Lesieur D,Mansour HA,Morgan P,Howell HE,Renard P,Caignard DH,Pfeiffer B,Delagrange P,Guardiola B

更新日期：1994-09-30 00:00:00

abstract：:Recently, the tryptophan-containing noncationizable opioid peptides emerged with atypical structure and unexpected in vivo activity. Herein, we describe analogs of the naturally occurring mixed κ/μ-ligand c[Phe-d-Pro-Phe-Trp] 1 (CJ-15,208). Receptor affinity, selectivity, and agonism/antagonism varied upon enlarging m...

journal_title：Journal of medicinal chemistry

authors： De Marco R,Bedini A,Spampinato S,Cavina L,Pirazzoli E,Gentilucci L

更新日期：2016-10-13 00:00:00

abstract：:A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7...

journal_title：Journal of medicinal chemistry

authors： Cignarella G,Barlocco D,Pinna GA,Loriga M,Tofanetti O,Germini M,Sala F

更新日期：1986-11-01 00:00:00

abstract：:The dopamine D(3) receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D(3) versus D(2) receptor-preferring ligands, the partial agonist BP 897 was taken as a lead structure. Variations in the spacer and the aryl moie...

journal_title：Journal of medicinal chemistry

authors： Hackling A,Ghosh R,Perachon S,Mann A,Höltje HD,Wermuth CG,Schwartz JC,Sippl W,Sokoloff P,Stark H

更新日期：2003-08-28 00:00:00

abstract：:A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavio...

journal_title：Journal of medicinal chemistry

authors： Mortensen DS,Rodriguez AL,Carlson KE,Sun J,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2001-11-08 00:00:00

abstract：:2-Hydroxy-5-(3,4-dichlorophenyl)-6,7-bis(hydroxymethyl)-2,3-dihydro-1H- pyrrolizine bis(2-propylcarbamate) (11) was prepared in a multistep synthesis. The 2-hydroxy group was used to prepare ester prodrugs 14 and 15, and the antineoplastic activities of 11, 14, and 15a were compared to 1 (the 2-deoxy analogue of 11) i...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Chang CP,McPherson HL Jr

更新日期：1983-09-01 00:00:00

abstract：:The ability of molecular docking, using the program Glide and an MM-GBSA postdocking scoring protocol, to correctly rank a number of congeneric kinase inhibitors was assessed. The approach was successful for the cases considered and suggests that this may be useful for the design of inhibitors in the lead optimization...

journal_title：Journal of medicinal chemistry

authors： Lyne PD,Lamb ML,Saeh JC

更新日期：2006-08-10 00:00:00

abstract：:The five dopamine receptor subtypes (D1-5) are activated by the endogenous catecholamine dopamine. Sustained research has sought to identify selective ligands for receptor subtypes. In particular, activation of the D1 receptor has attracted attention due to its promising role in neurological diseases. Initial attempts...

journal_title：Journal of medicinal chemistry

authors： Hall A,Provins L,Valade A

更新日期：2019-01-10 00:00:00

abstract：:Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute the peptide pharmacophore i...

journal_title：Journal of medicinal chemistry

authors： Van der Poorten O,Knuhtsen A,Sejer Pedersen D,Ballet S,Tourwé D

更新日期：2016-12-22 00:00:00

abstract：:NAD+-dependent histone deacetylases, sirtuins, cleave acetyl groups from lysines of histones and other proteins to regulate their activity. Identification of potent selective inhibitors would help to elucidate sirtuin biology and could lead to useful therapeutic agents. NAD+ has an adenosine moiety that is also presen...

journal_title：Journal of medicinal chemistry

authors： Trapp J,Jochum A,Meier R,Saunders L,Marshall B,Kunick C,Verdin E,Goekjian P,Sippl W,Jung M

更新日期：2006-12-14 00:00:00

abstract：:We report the syntheses of first-generation derivatives of isothiazolopyridones and their in vitro evaluation as antibacterial agents. These compounds, containing a novel heterocyclic nucleus composed of an isothiazolone fused to a quinolizin-4-one (at C-2 and C-3 of the quinolizin-4-one), were prepared using a sequen...

journal_title：Journal of medicinal chemistry

authors： Wiles JA,Hashimoto A,Thanassi JA,Cheng J,Incarvito CD,Deshpande M,Pucci MJ,Bradbury BJ

更新日期：2006-01-12 00:00:00

abstract：:The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in discovering selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo[1,5-a]pyrimidine scaffold as a potent inhibitor of Jak2....

journal_title：Journal of medicinal chemistry

authors： Hanan EJ,van Abbema A,Barrett K,Blair WS,Blaney J,Chang C,Eigenbrot C,Flynn S,Gibbons P,Hurley CA,Kenny JR,Kulagowski J,Lee L,Magnuson SR,Morris C,Murray J,Pastor RM,Rawson T,Siu M,Ultsch M,Zhou A,Sampath D,Ly

更新日期：2012-11-26 00:00:00

abstract：:Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a linking group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopy...

journal_title：Journal of medicinal chemistry

authors： Matsui T,Sugiura T,Nakai H,Iguchi S,Shigeoka S,Takada H,Odagaki Y,Nagao Y,Ushio Y,Ohmoto K

更新日期：1992-09-04 00:00:00

abstract：:Aliphatic amino acids glycine, alanine, valine, and leucine were conjugated to the antitumor drug N2-methyl-9-hydroxyellipticinium (NMHE) through a peroxidase-catalyzed oxidation reaction. NMR studies of the adducts so obtained have indicated (i) that the amino acids were linked to NMHE between the nitrogen of their p...

journal_title：Journal of medicinal chemistry

authors： Auclair C,Voisin E,Banoun H,Paoletti C,Bernadou J,Meunier B

更新日期：1984-09-01 00:00:00

abstract：:The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water so...

journal_title：Journal of medicinal chemistry

authors： Weeks MS,Hill CL,Schinazi RF

更新日期：1992-04-03 00:00:00

abstract：:Multivalent ligands are promising pharmacological tools that may be more efficacious for several diseases than highly selective single-target drugs. A combined therapy using dopaminergic agonists and adenosinergic antagonists is currently being evaluated for the treatment of Parkinson's disease. [(a) Kanda, T.; et al....

journal_title：Journal of medicinal chemistry

authors： Vendrell M,Angulo E,Casadó V,Lluis C,Franco R,Albericio F,Royo M

更新日期：2007-06-28 00:00:00

abstract：:The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected human cell systems, was found to suppress the integration of proviral DNA into the cellular DNA genome. In the present study 2 was tested with purified HIV-1 integr...

journal_title：Journal of medicinal chemistry

authors： Eich E,Pertz H,Kaloga M,Schulz J,Fesen MR,Mazumder A,Pommier Y

更新日期：1996-01-05 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：:(-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand the molec...

journal_title：Journal of medicinal chemistry

authors： Chu CK,Yadav V,Chong YH,Schinazi RF

更新日期：2005-06-16 00:00:00

abstract：:A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. ...

journal_title：Journal of medicinal chemistry

authors： Bailey DM,Hansen PE,Hlavac AG,Baizman ER,Pearl J,DeFelice AF,Feigenson ME

更新日期：1985-02-01 00:00:00

abstract：:The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a no...

journal_title：Journal of medicinal chemistry

authors： Kerwin JF Jr,Wagenaar F,Kopecka H,Lin CW,Miller T,Witte D,Stashko M,Nadzan AM

更新日期：1991-12-01 00:00:00

abstract：:The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at ...

journal_title：Journal of medicinal chemistry

authors： Jain RP,Pettersson HI,Zhang J,Aull KD,Fortin PD,Huitema C,Eltis LD,Parrish JC,James MN,Wishart DS,Vederas JC

更新日期：2004-12-02 00:00:00

abstract：:We report the results of a three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modeling investigation of the interaction of the enzyme 3-phosphoglycerate kinase (PGK) with aryl and alkyl bisphosphonates. For the human enzyme, the IC50 values are predicted within a factor of 2 ove...

journal_title：Journal of medicinal chemistry

authors： Kotsikorou E,Sahota G,Oldfield E

更新日期：2006-11-16 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：:Screening of our internal chemical collection against the neuropeptide Y5 (NPY Y5) receptor allowed the identification of a benzoxazine derivative 5f as a hit that showed moderate affinity (IC(50) = 300 nM). With the aim of improving the in vitro potency, a series of 2-benzoxazinone derivatives have been synthesized a...

journal_title：Journal of medicinal chemistry

authors： Torrens A,Mas J,Port A,Castrillo JA,Sanfeliu O,Guitart X,Dordal A,Romero G,Fisas MA,Sánchez E,Hernández E,Pérez P,Pérez R,Buschmann H

更新日期：2005-03-24 00:00:00

abstract：:Alkylation-elimination of adenine and 2-amino-6-chloropurine with gem-difluorocyclopropane dibromide 10 gave E- and Z-methylene-gem-difluorocyclopropanes 11a, 11b, 12a, and 12b and gem-difluorocyclopropenes 13a and 13b. Debenzylation of intermediates 11a, 11b, 12a, and 12b afforded E- and Z-methylenecyclopropanes 4a, ...

journal_title：Journal of medicinal chemistry

authors： Wang R,Ksebati MB,Corbett TH,Kern ER,Drach JC,Zemlicka J

更新日期：2001-11-08 00:00:00

abstract：:With the aim of obtaining new antitumoral agents, a series of 5,8-quinazolinediones was prepared. 5-Amino-6-methoxyquinazoline was oxidized by Fremy's salt to give 6-methoxy-5,8-quinazolinedione. Nucleophilic substitution reaction at C6, electrophilic substitution at C7, and synthesis of 7-amino-6-methoxy-5,8-quinazol...

journal_title：Journal of medicinal chemistry

authors： Renault J,Giorgi-Renault S,Baron M,Mailliet P,Paoletti C,Cros S,Voisin E

更新日期：1983-12-01 00:00:00