Inhibition of renin by substrate analogue inhibitors containing the olefinic amino acid 5(S)-amino-7-methyl-3(E)-octenoic acid.

abstract：:A series of benzyl-substituted phthalonitriles, substituted at the 3-, 4-, and 4,5-positions, underwent varied condensations with phthalonitrile to give a series of protected (monohydroxy- and polyhydroxyphthalocyaninato)zinc(II) derivatives which were readily cleaved to give several hydroxyphthalocyanines (ZnPc) (pht...

journal_title：Journal of medicinal chemistry

authors： Hu M,Brasseur N,Yildiz SZ,van Lier JE,Leznoff CC

更新日期：1998-05-21 00:00:00

abstract：:p38 MAP kinase has received considerable interest in the pharmaceutical industry and remains a valid and interesting target for the treatment of inflammation. To discover novel p38 inhibitors, we applied the ligand-based virtual screening technique, FieldScreen, to 1.2 million commercially available compounds. Fifty-e...

journal_title：Journal of medicinal chemistry

authors： Cheeseright TJ,Holm M,Lehmann F,Luik S,Göttert M,Melville JL,Laufer S

更新日期：2009-07-23 00:00:00

abstract：:Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine o...

journal_title：Journal of medicinal chemistry

authors： Tsou KC,Bender D,Santora N,David L,Damle S

更新日期：1976-06-01 00:00:00

abstract：:A series of 5-alkyl-2-(alkylthio)-6-(1-(2,6-difluorophenyl)propyl)-3,4-dihydropyrimidin-4(3H)-one derivatives (3a-h) belonging to the F(2)-DABOs class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) are endowed with a strong antiproliferative effect and induce cytodifferentiation in A375 melanoma cel...

journal_title：Journal of medicinal chemistry

authors： Sbardella G,Mai A,Bartolini S,Castellano S,Cirilli R,Rotili D,Milite C,Santoriello M,Orlando S,Sciamanna I,Serafino A,Lavia P,Spadafora C

更新日期：2011-08-25 00:00:00

abstract：:Novel antibiotics are urgently needed to combat the rise of infections due to drug-resistant microorganisms. Numerous natural nucleosides and their synthetically modified analogues have been reported to have moderate to good antibiotic activity against different bacterial and fungal strains. Nucleoside-based compounds...

journal_title：Journal of medicinal chemistry

authors： Serpi M,Ferrari V,Pertusati F

更新日期：2016-12-08 00:00:00

abstract：:Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...

journal_title：Journal of medicinal chemistry

authors： Furlotti G,Alisi MA,Apicella C,Capezzone de Joannon A,Cazzolla N,Costi R,Cuzzucoli Crucitti G,Garrone B,Iacovo A,Magarò G,Mangano G,Miele G,Ombrato R,Pescatori L,Polenzani L,Rosi F,Vitiello M,Di Santo R

更新日期：2012-11-26 00:00:00

abstract：:A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H 3 receptor inverse agonists. 2-Methyl-3-(4-[[3-(1-pyrrolidinyl)propyl]oxy]phenyl)-5-(trifluoromethyl)-4(3 H)-quinazolinone ( 1) was identified as a promising derivative for further evaluation following optimization of key paramet...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Mizutani T,Ishikawa S,Sekino E,Sasaki T,Fujimura T,Ito S,Mitobe Y,Miyamoto Y,Yoshimoto R,Tanaka T,Ishihara A,Takenaga N,Tokita S,Fukami T,Sato N

更新日期：2008-08-14 00:00:00

abstract：:One of the pattern recognition techniques, the SIMCA method, has been applied to structure-taste studies on L-aspartyl dipeptides (L-Asp-NH-R). The sweet and bitter taste class models of the peptides were obtained by using five structural descriptors, such as molar refractivity, and four kinds of STERIMOL parameters. ...

journal_title：Journal of medicinal chemistry

authors： Miyashita Y,Takahashi Y,Takayama C,Sumi K,Nakatsuka K,Ohkubo T,Abe H,Sasaki S

更新日期：1986-06-01 00:00:00

abstract：:The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically a...

journal_title：Journal of medicinal chemistry

authors： Li H,Huang Q,Chen C,Xu B,Wang HY,Long YQ

更新日期：2017-04-13 00:00:00

abstract：:Combretastatin A-4 (CA-4) in phosphate and serine pro-drug forms is under phase II clinical trials. With our interest of discovering CA-4 inspired new chemical entities, a novel series of 4,5-diaryl-2-aminoimidazole analogues of the compound was designed and synthesized by an efficient and diversity feasible route inv...

journal_title：Journal of medicinal chemistry

authors： Chaudhary V,Venghateri JB,Dhaked HP,Bhoyar AS,Guchhait SK,Panda D

更新日期：2016-04-14 00:00:00

abstract：:A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptos...

journal_title：Journal of medicinal chemistry

authors： Andersen KE,Braestrup C,Grønwald FC,Jørgensen AS,Nielsen EB,Sonnewald U,Sørensen PO,Suzdak PD,Knutsen LJ

更新日期：1993-06-11 00:00:00

abstract：:Bufotenine (5-hydroxy-N,N-dimethyltryptamine) has been reported to be behaviorally inactive or only very weakly active in man and animals; this may be a consequence of its low partition coefficient and resultant inability to penetrate the blood--brain barrier. The acetyl, propionyl, butyryl, isobutyryl, and pivalyl es...

journal_title：Journal of medicinal chemistry

authors： Glennon RA,Gessner PK,Godse DD,Kline BJ

更新日期：1979-11-01 00:00:00

abstract：:Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compoun...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Lin S,Aung TT,Lim F,Zou H,Bai Y,Li J,Lin H,Pang LM,Koh WL,Salleh SM,Lakshminarayanan R,Zhou L,Qiu S,Pervushin K,Verma C,Tan DT,Cao D,Liu S,Beuerman RW

更新日期：2015-01-22 00:00:00

abstract：:Starting from the high-throughput screening hit 1a, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors. ...

journal_title：Journal of medicinal chemistry

authors： Altmann E,Cowan-Jacob SW,Missbach M

更新日期：2004-11-18 00:00:00

abstract：:The 18 kDa translocator protein (TSPO) is a mitochondrial protein whose basal density is altered in several diseases, with the result that the evaluation of its expression levels by means of molecular imaging techniques represents a promising diagnostic approach. Experimental procedures using a labeled ligand often ca...

journal_title：Journal of medicinal chemistry

authors： Taliani S,Da Pozzo E,Bellandi M,Bendinelli S,Pugliesi I,Simorini F,La Motta C,Salerno S,Marini AM,Da Settimo F,Cosimelli B,Greco G,Novellino E,Martini C

更新日期：2010-05-27 00:00:00

abstract：:The important enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17 beta-HSD for reducing the levels of active steroids, we found that steroidal spiro-gamma-la...

journal_title：Journal of medicinal chemistry

authors： Sam KM,Auger S,Luu-The V,Poirier D

更新日期：1995-10-27 00:00:00

abstract：:A common pharmacophore for compounds structurally related to nitraquazone has been derived. Using this pharmacophore, new structures have been designed, synthesized, and evaluated for their inhibitory potencies against cyclic adenosine 5'-monophosphate (cAMP) specific phosphodiesterase (PDE 4). From these compounds, 4...

journal_title：Journal of medicinal chemistry

authors： Crespo MI,Pagès L,Vega A,Segarra V,López M,Doménech T,Miralpeix M,Beleta J,Ryder H,Palacios JM

更新日期：1998-10-08 00:00:00

abstract：:There is compelling evidence that Bax channel activity stimulates cytochrome c release leading ultimately to cell death, which is a key event in ischemic injuries and neurodegenerative diseases. Here 3,6-dibromocarbazole piperazine derivatives of 2-propanol are described as the first small and potent modulators of the...

journal_title：Journal of medicinal chemistry

authors： Bombrun A,Gerber P,Casi G,Terradillos O,Antonsson B,Halazy S

更新日期：2003-10-09 00:00:00

abstract：:A series of nondimethylphenyl-diarylpyrimidines with much lower cytotoxicities than their dimethyl analogues were developed. Compound B13 with a difluorobiphenyl moiety showed the highest antiviral activity against WT, mutant strains, and RT. The hydrochloride form of B13 exhibited an improved water solubility of 5.6 ...

journal_title：Journal of medicinal chemistry

authors： Sang Y,Han S,Pannecouque C,De Clercq E,Zhuang C,Chen F

更新日期：2019-12-26 00:00:00

abstract：:The concept of bioisosterism between benzimidazole and catechol was applied to the design and synthesis of benzimidazole analogues of norepinephrine, (R,S)-1-[5(6)-benzimidazolyl]-2-aminoethanol (2), and of isoproterenol, (R,S)-1-[5(6)-benzimidazolyl]-2-isopropylaminoethanol (4). Compound 2 was shown to be a partial b...

journal_title：Journal of medicinal chemistry

authors： Arnett CD,Wright J,Zenker N

更新日期：1978-01-01 00:00:00

abstract：:Two new peptides, tailored after Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (TRI), namely, Ac-Thr-D-Trp(CHO)-Phe-NMe alpha MeBzl (TRA) and Ac-Thr-D-Trp(CHO)-Oic-NMeBzl (TOI), in which Phe is replaced by (3aS, 7aS)-octahydroindole-2-carboxylic acid, proved more potent and selective NK1 antagonists. The conformational properties of a...

journal_title：Journal of medicinal chemistry

authors： Caliendo G,Grieco P,Perissutti E,Santagada V,Saviano G,Tancredi T,Temussi PA

更新日期：1997-02-14 00:00:00

abstract：:Following the observation that the activity of gonadotropin-releasing hormone III (GnRH-III) in the suppression of growth of MDA-MB-231 and MCF-7 breast cancer cells surpasses that of GnRH and other analogs thereof, analogs of GnRH-III were synthesized to investigate the structural basis for the improved antitumor act...

journal_title：Journal of medicinal chemistry

authors： Mezö I,Lovas S,Pályi I,Vincze B,Kálnay A,Turi G,Vadász Z,Seprödi J,Idei M,Tóth G,Gulyás E,Otvös F,Mák M,Horváth JE,Teplán I,Murphy RF

更新日期：1997-10-10 00:00:00

abstract：:(6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydropteroic acid was synthesized in several steps from 4,4-(ethylenedioxy)-cyclohexanone and [4-(tert-butyloxycarbonyl)benzyl]triphenylphosphonium bromide and was elaborated to (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-glutamic acid and (6R,6S)-5,8,10-trideaza-5,6,7,8-te...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Forsch RA,Moran RG

更新日期：1989-03-01 00:00:00

abstract：:The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluat...

journal_title：Journal of medicinal chemistry

authors： Meltzer PC,Blundell P,Jones AG,Mahmood A,Garada B,Zimmerman RE,Davison A,Holman BL,Madras BK

更新日期：1997-06-06 00:00:00

abstract：:Although the majority of proteins used for biomedical research are produced using living systems such as bacteria, biological means for producing proteins can be advantageously complemented by protein semisynthesis or total chemical synthesis. The latter approach is particularly useful when the proteins to be produced...

journal_title：Journal of medicinal chemistry

authors： Agouridas V,El Mahdi O,Melnyk O

更新日期：2020-12-24 00:00:00

abstract：:A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting comp...

journal_title：Journal of medicinal chemistry

authors： Oiry J,Pue JY,Imbach JL,Fatome M,Sentenac-Roumanou H,Lion C

更新日期：1986-11-01 00:00:00

abstract：:A series of N-substituted 3-aminoglutarimides have been synthesized and tested for inhibitory activity against a range of chemokines in vitro and for suppression of lipopolysaccharide-induced inflammation in vivo. The results show that they represent the first class of small molecules with broad-spectrum chemokine inh...

journal_title：Journal of medicinal chemistry

authors： Fox DJ,Reckless J,Warren SG,Grainger DJ

更新日期：2002-01-17 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：:(+)-12-Fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2a) and (+)-15-epi-12-fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2b) were prepared from the readily available (-)-7-fluorospiro[bicyclo[2.2.1]hept-5-ene-2,2'-[1,3]dioxolane]-7-methanol (3). Fluoroprostaglandins 2a and 2b possess truly signific...

journal_title：Journal of medicinal chemistry

authors： Grieco PA,Takigawa T

更新日期：1981-07-01 00:00:00

abstract：:Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resista...

journal_title：Journal of medicinal chemistry

authors： Teng P,Huo D,Nimmagadda A,Wu J,She F,Su M,Lin X,Yan J,Cao A,Xi C,Hu Y,Cai J

更新日期：2016-09-08 00:00:00