Peptide sweeteners. 4. Hydroxy and methoxy substitution of the aromatic ring in L-aspartyl-L-phenylalanine methyl ester. Structure-taste relationships.

abstract：:High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent tha...

journal_title：Journal of medicinal chemistry

authors： Duplantier AJ,Andresen CJ,Cheng JB,Cohan VL,Decker C,DiCapua FM,Kraus KG,Johnson KL,Turner CR,UmLand JP,Watson JW,Wester RT,Williams AS,Williams JA

更新日期：1998-06-18 00:00:00

abstract：:In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic...

journal_title：Journal of medicinal chemistry

authors： Talamas FX,Abbot SC,Anand S,Brameld KA,Carter DS,Chen J,Davis D,de Vicente J,Fung AD,Gong L,Harris SF,Inbar P,Labadie SS,Lee EK,Lemoine R,Le Pogam S,Leveque V,Li J,McIntosh J,Nájera I,Park J,Railkar A,Rajyagur

更新日期：2014-03-13 00:00:00

abstract：:In this paper, a peptide substrate (Pep8) of TSSK1 is identified. Using Pep8 as a substrate, two homogeneous and efficient assays for TSSK1 inhibitors screening have been developed, including luminescent kinase assay and LC-MS-based high-throughput assay. Two classes of compounds were identified that are able to effic...

journal_title：Journal of medicinal chemistry

authors： Zhang L,Yan Y,Liu Z,Abliz Z,Liu G

更新日期：2009-07-23 00:00:00

abstract：:We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship...

journal_title：Journal of medicinal chemistry

authors： Ghosh AK,Takayama J,Aubin Y,Ratia K,Chaudhuri R,Baez Y,Sleeman K,Coughlin M,Nichols DB,Mulhearn DC,Prabhakar BS,Baker SC,Johnson ME,Mesecar AD

更新日期：2009-08-27 00:00:00

abstract：:Use of automated synthesis led to the discovery of several 6-membered nitrogen heterocycles as replacements for the N-isoxazolyl substituent present in the 1-naphthalenesulfonamides endothelin-A (ETA) antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesu lfo namides (BMS 182874). In each of these ...

journal_title：Journal of medicinal chemistry

authors： Bradbury RH,Bath C,Butlin RJ,Dennis M,Heys C,Hunt SJ,James R,Mortlock AA,Sumner NF,Tang EK,Telford B,Whiting E,Wilson C

更新日期：1997-03-14 00:00:00

abstract：:Ether-linked glycero-alpha- and beta-D-glucopyranosides and glycero-1-thio-alpha- and beta-D-glucopyranosides have been synthesized by modifications of the Königs-Knorr procedure, and their antitumor activities have been evaluated. The bioactivities of these compounds have been evaluated in five different cell lines (...

journal_title：Journal of medicinal chemistry

authors： Guivisdalsky PN,Bittman R,Smith Z,Blank ML,Snyder F,Howard S,Salari H

更新日期：1990-09-01 00:00:00

abstract：:The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related di...

journal_title：Journal of medicinal chemistry

authors： Moore WJ,Kern JC,Bhat R,Commons TJ,Fukayama S,Goljer I,Krishnamurthy G,Magolda RL,Nogle L,Pitts K,Stauffer B,Trybulski EJ,Welmaker GS,Wilson M,Bodine PV

更新日期：2009-01-08 00:00:00

abstract：:Lysosomotropic detergents, which kill mammalian cells by disrupting lysosomal membranes, have now been found to be antifungals also. All strains in our assay are susceptible. The mode of action is as yet undetermined, but intracellular vacuoles may be the primary targets. ...

journal_title：Journal of medicinal chemistry

authors： Firestone RA,Pisano JM,Garrity GM,Fromtling RA,Zimmerman SB

更新日期：1987-08-01 00:00:00

abstract：:Protecting enkephalins, endogenous opioid peptides released in response to nociceptive stimuli, is an innovative approach for acute and neuropathic pain alleviation. This is achieved by inhibition of their enzymatic degradation by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptida...

journal_title：Journal of medicinal chemistry

authors： Poras H,Bonnard E,Dangé E,Fournié-Zaluski MC,Roques BP

更新日期：2014-07-10 00:00:00

abstract：:Three series of 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic esters were synthesized as part of a program to study potential anti-Leishmania drugs. These compounds were obtained by a condensation reaction of 4-chloro-1H-pyrazolo[3,4-b]pyridine with several aniline derivatives. Some of them were also obtained by a...

journal_title：Journal of medicinal chemistry

authors： de Mello H,Echevarria A,Bernardino AM,Canto-Cavalheiro M,Leon LL

更新日期：2004-10-21 00:00:00

abstract：:New beta-adrenergic blocking agents, most of which do not contain an aromatic nucleus, were synthesized. They were derived either from alkylamino-aliphatic oxime ethers or alkylamino-aliphatic ethers. Most active among these are O-[3-(tert-butylamino)-2-hydroxypropyl]acetoxime (8; trachea pA2 = 7.65) and 1-isobutoxy-3...

journal_title：Journal of medicinal chemistry

authors： Leclerc G,Bieth N,Schwartz J

更新日期：1980-06-01 00:00:00

abstract：:To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated produ...

journal_title：Journal of medicinal chemistry

authors： Huang GF,Okada M,De Clercq E,Torrence PF

更新日期：1981-04-01 00:00:00

abstract：:Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogena...

journal_title：Journal of medicinal chemistry

authors： DeGraw JI,Christie PH,Kisliuk RL,Gaumont Y,Sirotnak FM

更新日期：1990-01-01 00:00:00

abstract：:The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes,...

journal_title：Journal of medicinal chemistry

authors： Powers LJ,Fogt SW,Ariyan ZS,Rippin DJ,Heilman RD,Matthews RJ

更新日期：1981-05-01 00:00:00

abstract：:Extensive quantum chemical calculations have been made of the electronic distribution and conformational behavior of meperidine and desmethyl-, (+)-alpha, and (+)-beta-prodine using PCILO, a semiempirical molecular orbital method. For this series of opiates, a phenyl equatorial conformation was preferred over a phenyl...

journal_title：Journal of medicinal chemistry

authors： Loew GH,Jester JR

更新日期：1975-11-01 00:00:00

abstract：:A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC50 values below 100 nM for strand transfer and showed a 2 order of magnitude selectivity over 3'-processing. These strand transfer selective inhibitors also inhibited H...

journal_title：Journal of medicinal chemistry

authors： Costi R,Métifiot M,Chung S,Cuzzucoli Crucitti G,Maddali K,Pescatori L,Messore A,Madia VN,Pupo G,Scipione L,Tortorella S,Di Leva FS,Cosconati S,Marinelli L,Novellino E,Le Grice SF,Corona A,Pommier Y,Marchand C,Di San

更新日期：2014-04-24 00:00:00

abstract：:Modification of the 2(S)-methylbutyryl moiety of mevinolin led to a series of side chain ester derivatives. A systematic exploration of the structure-activity relationships showed that the introduction of an additional aliphatic group on the carbon alpha to the carbonyl group increased potency. This observation led to...

journal_title：Journal of medicinal chemistry

authors： Hoffman WF,Alberts AW,Anderson PS,Chen JS,Smith RL,Willard AK

更新日期：1986-05-01 00:00:00

abstract：:A novel series of nonpeptide angiotensin II (A II) antagonists containing a pyrimidinone ring which carries a C-linked biphenyltetrazole moiety and a carboxyheteroaryl group on the 3-position have been prepared. Their affinity for the AT1 receptor was determined in a binding assay on rat adrenal cortical membranes. Th...

journal_title：Journal of medicinal chemistry

authors： Salimbeni A,Canevotti R,Paleari F,Poma D,Caliari S,Fici F,Cirillo R,Renzetti AR,Subissi A,Belvisi L

更新日期：1995-11-24 00:00:00

abstract：:New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activ...

journal_title：Journal of medicinal chemistry

authors： Vidadala RS,Rivas KL,Ojo KK,Hulverson MA,Zambriski JA,Bruzual I,Schultz TL,Huang W,Zhang Z,Scheele S,DeRocher AE,Choi R,Barrett LK,Siddaramaiah LK,Hol WG,Fan E,Merritt EA,Parsons M,Freiberg G,Marsh K,Kempf DJ,Ca

更新日期：2016-07-14 00:00:00

abstract：:The antiproliferative activity of the 14 isomeric monoxylosylated dihydroxynaphthalenes has been tested in vitro toward normal HFL-1 and 3T3 A31 cells as well as transformed T24 and 3T3 SV40 cells. The antiproliferative effect toward HFL-1 cells was correlated with the polarity of the compounds. However, in the case o...

journal_title：Journal of medicinal chemistry

authors： Jacobsson M,Ellervik U,Belting M,Mani K

更新日期：2006-03-23 00:00:00

abstract：:Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex...

journal_title：Journal of medicinal chemistry

authors： Lemaire S,Yamashiro D,Li CH

更新日期：1976-03-01 00:00:00

abstract：:AFTIR (after flowing through immobilized receptor) is a novel method for screening herbal extracts for pharmaceutical properties. Using AFTIR, we identified Cynarin in Echinacea purpurea by its selective binding to chip immobilized CD28, a receptor of T-cells, which is instrumental to immune functioning. The results o...

journal_title：Journal of medicinal chemistry

authors： Dong GC,Chuang PH,Forrest MD,Lin YC,Chen HM

更新日期：2006-03-23 00:00:00

abstract：:Peptidyl alpha-keto amides have been synthesized and tested as inhibitors of the cysteine protease calpain. A stereospecific synthesis was devised in which Cbz-dipeptidyl-alpha-hydroxy amides were oxidized with TEMPO/hypochlorite to the corresponding alpha-keto amides. This oxidation was accomplished in good yields an...

journal_title：Journal of medicinal chemistry

authors： Harbeson SL,Abelleira SM,Akiyama A,Barrett R 3rd,Carroll RM,Straub JA,Tkacz JN,Wu C,Musso GF

更新日期：1994-09-02 00:00:00

abstract：:A novel bitriazolyl acyclonucleoside was discovered to exhibit powerful antiproliferative effects on different cancer cell lines through caspase-dependent apoptosis and at the same time stimulate the immune response in dendritic cells via Toll-like receptor 7 (TLR7) signaling. This promising compound with dual antican...

journal_title：Journal of medicinal chemistry

authors： Xia Y,Wang M,Demaria O,Tang J,Rocchi P,Qu F,Iovanna JL,Alexopoulou L,Peng L

更新日期：2012-06-14 00:00:00

abstract：:A dihydropyridine-pyridine type redox pro-drug system was developed for delivering quaternary pyridinium salts through biological membranes. As a first application, the dihydropyridine derivative of N-methylpyridinium-2-carbaldoxime chloride (2-PAM) was synthesized using a reduction-addition-elimination sequence. The ...

journal_title：Journal of medicinal chemistry

authors： Bodor N,Shek E,Higuchi T

更新日期：1976-01-01 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：:A series of 2-guanidino-4-oxoimidazoline (deoxo-IZ) derivatives was prepared and showed potent antimalarial activities in rodent and Rhesus models. Compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by or...

journal_title：Journal of medicinal chemistry

authors： Liu X,Wang X,Li Q,Kozar MP,Melendez V,O'Neil MT,Lin AJ

更新日期：2011-07-14 00:00:00

abstract：:The tetrapeptide sequence His-Phe-Arg-Trp, derived from melanocyte-stimulating hormone (alphaMSH) and its analogs, causes a decrease in food intake and elevates energy utilization upon binding to the melanocortin-4 receptor (MC4R). To utilize this sequence as an effective agent for treating obesity, we improved its me...

journal_title：Journal of medicinal chemistry

authors： Hess S,Linde Y,Ovadia O,Safrai E,Shalev DE,Swed A,Halbfinger E,Lapidot T,Winkler I,Gabinet Y,Faier A,Yarden D,Xiang Z,Portillo FP,Haskell-Luevano C,Gilon C,Hoffman A

更新日期：2008-02-28 00:00:00

abstract：:A number of cycloalkyl substituents (from C-3 to C-8) have been introduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guano...

journal_title：Journal of medicinal chemistry

authors： Vittori S,Lorenzen A,Stannek C,Costanzi S,Volpini R,IJzerman AP,Kunzel JK,Cristalli G

更新日期：2000-01-27 00:00:00

abstract：:A series of tetramisole derivatives was synthesized and tested for inhibitory activity against alkaline phosphatase which was partially purified from a murine ascitic neoplasm resistant to 6-thiopurines (Sarcoma 180/TG). These agents included derivatives substituted with halogens, CH3, or NO2 groups at either the meta...

journal_title：Journal of medicinal chemistry

authors： Bhargava KK,Lee MH,Huang Y,Cunningham LS,Agrawal KC,Sartorelli AC

更新日期：1977-04-01 00:00:00