abstract：:Z-1,1-Dichloro-2,3-diphenylcyclopropane (1) is an effective anti-breast cancer agent in rodents and in cell culture. We recently determined that 1 inhibits tubulin assembly in vitro and causes microtubule loss in breast cancer cells, leading to accumulation in the G2/M portion of the cell cycle. Aryl ring-halogenated,...

journal_title：Bioorganic & medicinal chemistry

authors： Jonnalagadda SS,ter Haar E,Hamel E,Lin CM,Magarian RA,Day BW

更新日期：1997-04-01 00:00:00

abstract：:Three new derivatives of 2-substituted 1,3,4-thiadiazole-5-sulfonamide have been synthesized. These compounds are 2-(3-chloropropionylamino)-1,3,4-thiadiazole-5-sulfonamide (1); 2-(2,2-dichloroacetylamino)-1,3,4-thiadiazole-5-sulfonamide (2); and 2-(3-phenylpropionylamino)-1,3,4-thiadiazole-5-sulfonamide (3). Inhibiti...

journal_title：Bioorganic & medicinal chemistry

authors： Arslan O,Küfrevioĝlu OI,Nalbantoĝlu B

更新日期：1997-03-01 00:00:00

abstract：:Thionation of estrogen-like active cyclic peptides, segetalins A (1) and B (2), with Lawesson's reagent provided each two thiosegetalins; thiosegetalin A1 [Gly-1-psi(CS-NH)-Val-2; Trp-5-psi (CS-NH)-Ala-6]segetalin A, thiosegetalin A2 [Gly-1-psi(CS-NH)-Val-2; Ala-6-psi(CS-NH)-Gly-1]segetalin A, thiosegetalin B1 [Gly-1-...

journal_title：Bioorganic & medicinal chemistry

authors： Morita H,Yun YS,Takeya K,Itokawa H,Shirota O

更新日期：1997-03-01 00:00:00

abstract：:2-(2-Acetoxyethyl)cyclohexanone (4) was converted into the lactone (-)-(5) regio- and enantioselectively using 2-oxo-delta 3-4,5,5-trimethylcyclopentenyl acetyl-CoA monooxygenase, an NADPH-dependent Baeyer-Villiger monooxygenase from camphor grown Pseudomonas putida NCIMB 10007. The lactone (-)-(5) was converted into ...

journal_title：Bioorganic & medicinal chemistry

authors： Adger B,Bes MT,Grogan G,McCague R,Pedragosa-Moreau S,Roberts SM,Villa R,Wan PW,Willetts AJ

更新日期：1997-02-01 00:00:00

abstract：:Ionophoric properties of dipyrazolic crowns and podands containing a 1,3-bis(1H-pyrazol-1-yl)propane unit in their structure are described. They show selectivity of ammonium vs alkali cations and interesting norepinephrine transport rates. A molecular modelling study has been used to elucidate the superstructures of t...

journal_title：Bioorganic & medicinal chemistry

authors： Rodríguez-Franco MI,Fierros M,Martínez A,Navarro P,Conde S

更新日期：1997-02-01 00:00:00

abstract：:Semipeptoids derived from the Ras farnesyl transferase inhibitor, CVFM, were synthesized by the Simultaneous Multiple Analogue Peptide Synthesis methodology. The semipeptoids were screened for their in vitro inhibition potency towards farnesyl transferase and geranylgeranyl transferase. Structure-activity relationship...

journal_title：Bioorganic & medicinal chemistry

authors： Reuveni H,Gitler A,Poradosu E,Gilon C,Levitzki A

更新日期：1997-01-01 00:00:00

abstract：:Cyclosporin A (CsA) can be regiospecifically alkylated at the NH of Val-5 with reactive bromides in the presence of phosphazene-base P4-t-Bu to yield derivatives 2-5. These are devoid of immunosuppressive activity in vitro but they have binding affinity for cyclophilin A (CypA) similar to that of CsA and thus represen...

journal_title：Bioorganic & medicinal chemistry

authors： Papageorgiou C,Kallen J,France J,French R

更新日期：1997-01-01 00:00:00

abstract：:Various dihydroxyacetone-phosphate (DHAP) analogues bearing an aromatic ring or beta-dicarbonyl structures were synthesized. Their capacity to form a stabilized iminium ion or conjugated enamine in the reaction catalyzed by rabbit muscle aldolase (EC 4.1.2.13) were investigated by enzymatic kinetics and UV difference ...

journal_title：Bioorganic & medicinal chemistry

authors： Gefflaut T,Blonski C,Périé J

更新日期：1996-12-01 00:00:00

abstract：:The problems inherent in the enzymatic and chemical synthesis of S-adenosyl-L-methionine (SAM) led us to develop an efficient, simple method for the synthesis of large amounts of labeled SAM. Previously, we reported that the problem of product inhibition of E. coli SAM synthetase encoded by the metK gene was successfu...

journal_title：Bioorganic & medicinal chemistry

authors： Park J,Tai J,Roessner CA,Scott AI

更新日期：1996-12-01 00:00:00

abstract：:The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-) (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were synthesized. The corresponding aldonolactones (1, 7 and 11) or aldonic acid ester (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5-a...

journal_title：Bioorganic & medicinal chemistry

authors： Godskesen M,Lundt I,Madsen R,Winchester B

更新日期：1996-11-01 00:00:00

abstract：:The binding specificities of the closely related lectins from Canavalia ensiformis and Dioclea grandiflora were examined using specifically O-alkylated mono- and disaccharides. Both lectins accept any substitution at the monosaccharide C2 hydroxyl group. The binding energy of C2-alkylated ligands-concanavalin A comple...

journal_title：Bioorganic & medicinal chemistry

authors： Chervenak MC,Toone EJ

更新日期：1996-11-01 00:00:00

abstract：:As part of a continuing effort aimed at the development of selective, efficacious, and centrally active m1 muscarinic agonists for the treatment of Alzheimer's disease, a series of amide and hydrazide amidine derivatives (2a-e and 3b-d) was synthesized and examined for muscarinic agonist activity. Preliminary biochemi...

journal_title：Bioorganic & medicinal chemistry

authors： Ojo B,Dunbar PG,Durant GJ,Nagy PI,Huzl JJ 3rd,Periyasamy S,Ngur DO,el-Assadi AA,Hoss WP,Messer WS Jr

更新日期：1996-10-01 00:00:00

abstract：:A novel artificial peptide named HPH-Pep, comprising a pyridine and two histidine units, was synthesized. The HPH-Pep-CuII complex had unique pentacoordinated structure as shown by X-ray crystallography and exhibited superoxide-scavenging activity as indicated by ESR spectroscopy. The superoxide-quenching profile of H...

journal_title：Bioorganic & medicinal chemistry

authors： Otsuka M,Satake H,Murakami S,Doi M,Ishida T,Shibasaki M,Sugiura Y

更新日期：1996-10-01 00:00:00

abstract：:To streamline the preclinical phase of pharmaceutical development, we have explored the utility of structural data on the molecular target and synergy between computational and medicinal chemistry. We have concentrated on parasitic infectious diseases with a particular emphasis on the development of specific noncovale...

journal_title：Bioorganic & medicinal chemistry

authors： Li R,Chen X,Gong B,Selzer PM,Li Z,Davidson E,Kurzban G,Miller RE,Nuzum EO,McKerrow JH,Fletterick RJ,Gillmor SA,Craik CS,Kuntz ID,Cohen FE,Kenyon GL

更新日期：1996-09-01 00:00:00

abstract：:The recent interest in inhibitors of farnesyl:protein transferase (FPTase) has resulted in a better understanding of the enzymology of this protein. Rationally designed inhibitors of prenyl transfer have emerged as potential new drug candidates because of the insight gained over how a prenyl group is enzymatically tra...

journal_title：Bioorganic & medicinal chemistry

authors： Scholten JD,Zimmerman K,Oxender M,Sebolt-Leopold J,Gowan R,Leonard D,Hupe DJ

更新日期：1996-09-01 00:00:00

abstract：:The cells of Bacillus stearothermophilus contain an NADH-dependent diacetyl (acetoin) reductase. The enzyme was easily purified to homogeneity, partially characterised, and found to be composed of two subunits with the same molecular weight. In the presence of NADH, it catalyses the stereospecific reduction of diacety...

journal_title：Bioorganic & medicinal chemistry

authors： Giovannini PP,Medici A,Bergamini CM,Rippa M

更新日期：1996-08-01 00:00:00

abstract：:3-Amino-2-hydroxy-propionaldehydes [H2NCH(R)CHOHCHO with R = H, i-Bu, CH2Ph] were designed as metallo-aminopeptidase inhibitors based on the metal active site chelation concept. These compounds were found to be micromolar inhibitors of aminopeptidase-M (AP-M, EC 3.4.11.2) with potencies similar to bestatin (Ki = 3.5 m...

journal_title：Bioorganic & medicinal chemistry

authors： Tarnus C,Rémy JM,d'Orchymont H

更新日期：1996-08-01 00:00:00

abstract：:Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a Cl atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with f...

journal_title：Bioorganic & medicinal chemistry

authors： Komai T,Higashida S,Sakurai M,Nitta T,Kasuya A,Miyamaoto S,Yagi R,Ozawa Y,Handa H,Mohri H,Yasuoka A,Oka S,Nishigaki T,Kimura S,Shimada K,Yabe Y

更新日期：1996-08-01 00:00:00

abstract：:The irreversible inhibition of histidine ammonia lyase by L-cysteine and dioxygen has been reexamined. After denaturation and consecutive digestion of the inhibited enzyme by trypsin and endoproteinase Glu-C, the generated chromophoric system (lambda max = 340 nm) remained intact and was isolated in an octapeptide con...

journal_title：Bioorganic & medicinal chemistry

authors： Weber K,Rétey J

更新日期：1996-07-01 00:00:00

abstract：:In archaea the first general tetrapyrrole precursor 5-aminolevulinic acid (ALA) is formed via the tRNA-dependent five-carbon pathway from glutamate. We have cloned the hemA gene encoding the central enzyme of the pathway glutamyl-tRNA reductase from the methanogenic archaeon Methanobacterium thermoautotrophicum by com...

journal_title：Bioorganic & medicinal chemistry

authors： Hungerer C,Weiss DS,Thauer RK,Jahn D

更新日期：1996-07-01 00:00:00

abstract：:Scutione (1), a new norquinonemethide triterpene with a netzahualcoyene type skeleton, has been isolated from the root bark of Maytenus scutioides (Celastraceae) by bioactivity-directed fractionation. The structure of 1 has been elucidated by means of 1H and 13C NMR spectroscopic studies, including 1H-13C heteronuclea...

journal_title：Bioorganic & medicinal chemistry

authors： González AG,Alvarenga NL,Ravelo AG,Bazzocchi IL,Ferro EA,Navarro AG,Moujir LM

更新日期：1996-06-01 00:00:00

abstract：:A molecular modeling study meant to detect pharmacophore-like patterns in the active site of trypanothione reductase (TR) offered hints about the opportunity of synthesizing and testing diphenylsulfide derivatives with prolonged or branched polyamino side chains as putative TR inhibitors. The inhibition results within...

journal_title：Bioorganic & medicinal chemistry

authors： Baillet S,Buisine E,Horvath D,Maes L,Bonnet B,Sergheraert C

更新日期：1996-06-01 00:00:00

abstract：:A novel scaffold system for the generation of diversity libraries has been designed which allows for rapid modification not only of functional groups, but their spatial arrangements as well. The biphenyl scaffold allows for display of three or four diverse functional groups in a wide variety of spatial arrangements de...

journal_title：Bioorganic & medicinal chemistry

authors： Pavia MR,Cohen MP,Dilley GJ,Dubuc GR,Durgin TL,Forman FW,Hediger ME,Milot G,Powers TS,Sucholeiki I,Zhou S,Hangauer DG

更新日期：1996-05-01 00:00:00

abstract：:A series of ophiobolins were isolated from a fungal extract based on their nematocidal activity. These compounds are non-competitive inhibitors of ivermectin binding to membranes prepared from the free-living nematode, Caenorhabditis elegans, with an inhibition constant of 15 microM. The ophiobolins which were most po...

journal_title：Bioorganic & medicinal chemistry

authors： Tsipouras A,Adefarati AA,Tkacz JS,Frazier EG,Rohrer SP,Birzin E,Rosegay A,Zink DL,Goetz MA,Singh SB,Schaeffer JM

更新日期：1996-04-01 00:00:00

abstract：:We examined the in vitro and in vivo natural killer (NK) cell activity enhancing effects of alpha-, beta-galactosylceramide (GalCer) and alpha-, beta-glucosylceramide (GluCer) which have the same ceramide moiety, and of other alpha-, beta-GalCer having a different ceramide portion, and found that alpha-types show stro...

journal_title：Bioorganic & medicinal chemistry

authors： Kobayashi E,Motoki K,Yamaguchi Y,Uchida T,Fukushima H,Koezuka Y

更新日期：1996-04-01 00:00:00

abstract：:Five hydroxylated aliphatic molecules were identified as the pheromone produced by male West Indian Sugarcane Borer (WISB): 4-methyl-5-nonanol (1), 2-methyl-4-heptanol (2), 2-methyl-4-octanol (3), 5-nonanol (4) and 3-hydroxy-4-methyl-5-nonanone (5). Electroantennographic recordings revealed antennal responses to compo...

journal_title：Bioorganic & medicinal chemistry

authors： Ramirez-Lucas P,Malosse C,Ducrot PH,Lettere M,Zagatti P

更新日期：1996-03-01 00:00:00

abstract：:Several analogues of (Z)-8-dodecenyl acetate (1a), the major pheromone component of the Oriental fruit moth, Cydia molesta, with chloroformate and lactone functional groups in place of the acetate moiety, were synthesized and investigated for their biological activity at four evaluation levels, i.e. by electroantennog...

journal_title：Bioorganic & medicinal chemistry

authors： Hoskovec M,Hovorka O,Kalinová B,Koutek B,Streinz L,Svatos A,Sebek P,Saman D,Vrkoc J

更新日期：1996-03-01 00:00:00

abstract：:A series of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives (B) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (3H-OXO-M) and [3H]-pirenzepine (3H-PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined usi...

journal_title：Bioorganic & medicinal chemistry

authors： Plate R,Plaum MJ,de Boer T,Andrews JS,Rae DR,Gibson S

更新日期：1996-02-01 00:00:00

abstract：:The molecular design and chemical synthesis of novel enediyne molecules related to the neocarzinostatin chromophore (1), and their chemical and DNA cleaving properties are described. The 10-membered enediyne triols 16-18 were effectively synthesized from xylitol (10) in a short step, and found to be quite stable when ...

journal_title：Bioorganic & medicinal chemistry

authors： Toshima K,Ohta K,Kano T,Nakamura T,Nakata M,Kinoshita M,Matsumura S

更新日期：1996-01-01 00:00:00

abstract：:(N-1',1'-Dimethylethyl)-3-haloandrost-3,5-diene-17 beta-carboxamides (9-11) and the methyl ester 8 were prepared from 3-chloro/bromoandrost-3,5-diene-17 beta-carboxylic chloride/bromide (6/7), which were obtained from pregnenolone. In comparison with finasteride and 4-MA, compounds 8-11 showed very weak inhibitory act...

journal_title：Bioorganic & medicinal chemistry

authors： Li X,Singh SM,Luu-The V,Côté J,Laplante S,Labrie F

更新日期：1996-01-01 00:00:00

abstract：:A series of 3-N,N-di-n-propylamino-2-chromanones were synthesized as dopamine analogues. The lactone ring was introduced as a means to reduce their propensity to cross the blood-brain barrier and to avoid central side effects, rendering these compounds potentially useful for the treatment of glaucoma. Pharmacological ...

journal_title：Bioorganic & medicinal chemistry

authors： Benoit-Guyod M,Nicolle E,Namil A,Coulombeau C,Leclerc G

更新日期：1995-12-01 00:00:00

abstract：:To characterize the structure-activity relationship between alpha 1-adrenergic receptors and the family of imidazoline/guanidinium receptive sites (IGRS), we synthesized and characterized a series of analogues of cirazoline, an imidazoline with high affinity for alpha 1-adrenergic receptors and IGRS. Analysis of poten...

journal_title：Bioorganic & medicinal chemistry

authors： Brasili L,Pigini M,Marucci G,Quaglia W,Malmusi L,Lanier SM,Lanier B

更新日期：1995-11-01 00:00:00

abstract：:A new kaurane type diterpene lactone, neotripterifordin (1), has been isolated from the roots of Tripterygium wilfordii. The structure of 1 was elucidated by spectroscopic methods, which included the concerted application of a number of 2-D NMR techniques including 1H-1H COSY, phase-sensitive NOESY, HETCOR, and long-r...

journal_title：Bioorganic & medicinal chemistry

authors： Chen K,Shi Q,Fujioka T,Nakano T,Hu CQ,Jin JQ,Kilkuskie RE,Lee KH

更新日期：1995-10-01 00:00:00

abstract：:A series of 3- and 4-(sulfo- and sulfonamidoalkyl)pyridine and piperidine-2-carboxylic acid derivatives as analogs of NMDA receptor antagonists was prepared. Affinity for the NMDA receptor was determined by binding assays using the specific radioligand [3H] (2SR,4RS)-4-(phosphonomethyl)piperidine-2-carboxylic acid (CG...

journal_title：Bioorganic & medicinal chemistry

authors： el Hadri A,Maldivi P,Leclerc G,Rocher JP

更新日期：1995-09-01 00:00:00

abstract：:The three-dimensional structure of the endothelin B receptor (ETB) selective antagonist RES-701-1 has been determined by 1H NMR in deuterated dimethyl sulphoxide. RES-701-1 consists of 16 amino acid residues with a novel internal linkage between the beta-carboxyl group of Asp9 and the alpha-amino group of Gly1. The st...

journal_title：Bioorganic & medicinal chemistry

authors： Katahira R,Shibata K,Yamasaki M,Matsuda Y,Yoshida M

更新日期：1995-09-01 00:00:00

abstract：:We report structure-activity investigations in a series of tripeptide amide inhibitors of thrombin, and the development of a series of highly potent active site directed alpha-keto carbonyl inhibitors having the side chain of lysine at P1. Compounds of this class are unstable by virtue of reactivity at the electrophil...

journal_title：Bioorganic & medicinal chemistry

authors： Brady SF,Sisko JT,Stauffer KJ,Colton CD,Qiu H,Lewis SD,Ng AS,Shafer JA,Bogusky MJ,Veber DF

更新日期：1995-08-01 00:00:00

abstract：:A series of new N-substituted aminohydroxypyridines have been synthesized, pharmacologically evaluated and compared with their N-substituted oxazolopyridone analogs. The compound with the maximal combination of safety and analgesic efficacy was 3-[2-[4-(4-fluorophenyl)-1-piperazinyl]ethyl]amino-2-hydroxypyridine (comp...

journal_title：Bioorganic & medicinal chemistry

authors： Viaud MC,Jamoneau P,Bizot-Espiard JG,Pfeiffer B,Renard P,Caignard DH,Adam G,Guillaumet G

更新日期：1995-07-01 00:00:00

abstract：:The three trimethylammonium salts 3-5 proved to be 100 times more efficient at alkylating DNA than 2 and exhibited DNA alkylation efficiencies identical to that of (+)-CC-1065 (1). In addition, the agents 3 and 4 exhibited DNA alkylation selectivities identical to that of 2. This may be attributed to spatially well-de...

journal_title：Bioorganic & medicinal chemistry

authors： Boger DL,Yun W,Han N,Johnson DS

更新日期：1995-06-01 00:00:00

abstract：:A complete characterization of DNA binding agents requires that their mode of binding to DNA be established. In the absence of high resolution structural data, the mode of binding is, of necessity, usually inferred indirectly from various solution studies. The purpose of this study is to show that only certain methods...

journal_title：Bioorganic & medicinal chemistry

authors： Suh D,Chaires JB

更新日期：1995-06-01 00:00:00

abstract：:RNA cleavage by enediyne anticancer antibiotics was shown to occur with no apparent sequence selectivity, but RNA structure appears to be important in those substrates where cleavage was observed. Neocarzinostatin (NCS) cleaved a wider variety of RNA substrates than either esperamicin (ESP) or calicheamicin (CAL), and...

journal_title：Bioorganic & medicinal chemistry

authors： Battigello JM,Cui M,Roshong S,Carter BJ

更新日期：1995-06-01 00:00:00