Large scale preparation of chiral building blocks for the P3 site of renin inhibitors.


:Racemic ethyl 2-benzyl-3-(tert-butylsulfonyl)propionate (1) and racemic ethyl 2-benzyl-3-[[1-methyl-1-((morpholin-4-yl)carbonyl)ethyl]sulfonyl] propionate (3) were enantioselectively hydrolyzed by subtilisin Carlsberg generating the respective (S)-acids used as building blocks for renin inhibitors. The esters were readily converted as emulsions at elevated temperature, in a suspended form or a two-phase-liquid system. The enzyme maintained its excellent selectivity and a good activity also at high initial substrate concentrations (up to 50% w/w). The enzymatic reaction and work-up were optimized and scaled up. Emulsion problems during work-up encountered with these highly concentrated mixtures were solved by application of a disk separator for phase separation.


Bioorg Med Chem


Doswald S,Estermann H,Kupfer E,Stadler H,Walther W,Weisbrod T,Wirz B,Wostl W




Has Abstract


1994-06-01 00:00:00














  • pH-dependent production of himeic acid A and its non-enzymatic conversions to himeic acids B and C.

    abstract::The fungus Aspergillus japonicus MF275 produces himeic acid A (1), containing a 4-pyrone ring, along with its congeners, himeic acids B (2) and C (3). During culture, 1 was gradually converted to 3, the corresponding 4-pyridone derivative. A study of the relationship between the culture pH and the fungal metabolites s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Katsuki A,Kato H,Tahara Y,Hashimoto M,Fujii I,Tsukamoto S

    更新日期:2018-05-01 00:00:00

  • A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects.

    abstract::A series of benzene sulfonamide carbonic anhydrase (CA, EC inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Carta F,Di Cesare Mannelli L,Pinard M,Ghelardini C,Scozzafava A,McKenna R,Supuran CT

    更新日期:2015-04-15 00:00:00

  • Theoretical research in structure characteristics of different inhibitors and differences of binding modes with CBP bromodomain.

    abstract::The CBP (CREB (cAMP responsive element binding protein) binding protein) bromodomain (BRD) could recognize and bind with acetyl K382 of human tumor suppressor protein p53 which the mutation of encoding gene might cause human cancers. CBP-BRD serves as a promising drug target for several disease pathways and a series o...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang XS,Zheng QC

    更新日期:2018-02-01 00:00:00

  • Anti-inflammatory properties of a heparin-like glycosaminoglycan with reduced anti-coagulant activity isolated from a marine shrimp.

    abstract::The anti-inflammatory properties of a heparin-like compound from the shrimp Litopenaeus vannamei are related. Besides reducing significantly (p<0.001) the influx of inflammatory cells to injury site in a model of acute inflammation, shrimp heparin-like compound was able to reduce the matrix metalloproteinase (MMPs) ac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brito AS,Arimatéia DS,Souza LR,Lima MA,Santos VO,Medeiros VP,Ferreira PA,Silva RA,Ferreira CV,Justo GZ,Leite EL,Andrade GP,Oliveira FW,Nader HB,Chavante SF

    更新日期:2008-11-01 00:00:00

  • Structural study of four-stranded quadruplex structures containing 2'-deoxy-8-(propyn-1-yl)adenosine.

    abstract::In this paper, we report the NMR structural study of two quadruplex structures formed by truncations of the human telomeric sequence and containing a modified base, namely d(AprGGGT) and d(TAprGGGT), where Apr indicates 2'-deoxy-8-(propyn-1-yl)adenosines. Both oligonucleotides have been found to form 4-fold symmetric ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Esposito V,Randazzo A,Galeone A,Varra M,Mayol L

    更新日期:2004-03-01 00:00:00

  • Synthesis and preliminary in vivo evaluation of new [18F]fluoro-inositols as Positron Emission Tomography radiotracers.

    abstract::This study describes the synthesis and radiosynthesis of eight new [18F]fluoro-inositol-based radiotracers in myo- and scyllo-inositol configuration. These radiotracers are equipped with a propyl linker bearing fluorine-18. This fluorinated arm is either on a hydroxyl group, i.e. O-alkylated inositols, or on the cyclo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Collet C,Schmitt S,Maskali F,Clément A,Chrétien F,Karcher G,Marie PY,Poussier S,Lamandé-Langle S

    更新日期:2017-10-15 00:00:00

  • Synthesis, biological evaluation, and molecular modeling of cinnamic acyl sulfonamide derivatives as novel antitubulin agents.

    abstract::A series of novel cinnamic acyl sulfonamide derivatives (9a-16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Luo Y,Qiu KM,Lu X,Liu K,Fu J,Zhu HL

    更新日期:2011-08-15 00:00:00

  • CYP19 (aromatase): exploring the scaffold flexibility for novel selective inhibitors.

    abstract::Several derivatives out of a series of antifungal agents exhibited a good inhibitory potency against aromatase as well as a fairly good selectivity toward CYP17, even if lacking H-bond accepting substituents. Their common structural feature is a flexible backbone that did not fit into previously reported CYP19 models....

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Castellano S,Stefancich G,Ragno R,Schewe K,Santoriello M,Caroli A,Hartmann RW,Sbardella G

    更新日期:2008-09-15 00:00:00

  • Antimalarial acridines: synthesis, in vitro activity against P. falciparum and interaction with hematin.

    abstract::A series of acridine derivatives were synthesised and their in vitro antimalarial activity was evaluated against one chloroquine-susceptible strain (3D7) and three chloroquine-resistant strains (W2, Bre1 and FCR3) of Plasmodium falciparum. Structure-activity relationship showed that two positives charges as well as 6-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Guetzoyan L,Yu XM,Ramiandrasoa F,Pethe S,Rogier C,Pradines B,Cresteil T,Perrée-Fauvet M,Mahy JP

    更新日期:2009-12-01 00:00:00

  • Predicting antitrichomonal activity: a computational screening using atom-based bilinear indices and experimental proofs.

    abstract::Existing Trichomonas vaginalis therapies are out of reach for most trichomoniasis people in developing countries and, where available, they are limited by their toxicity (mainly in pregnant women) and their cost. New antitrichomonal agents are needed to combat emerging metronidazole-resistant trichomoniasis and reduce...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Marrero-Ponce Y,Meneses-Marcel A,Castillo-Garit JA,Machado-Tugores Y,Escario JA,Barrio AG,Pereira DM,Nogal-Ruiz JJ,Arán VJ,Martínez-Fernández AR,Torrens F,Rotondo R,Ibarra-Velarde F,Alvarado YJ

    更新日期:2006-10-01 00:00:00

  • Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111.

    abstract::We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1-4)βGlcA(1-]2 and CS-DD [-3)βGalNAc6S(1-4)βGlcA2S(1-]2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Matsushita K,Nakata T,Takeda-Okuda N,Nadanaka S,Kitagawa H,Tamura JI

    更新日期:2018-03-01 00:00:00

  • Synergistic reduction of HIV-1 infectivity by 5-azacytidine and inhibitors of ribonucleotide reductase.

    abstract::Although many compounds have been approved for the treatment of human immunodeficiency type-1 (HIV-1) infection, additional anti-HIV-1 drugs (particularly those belonging to new drug classes) are still needed due to issues such as long-term drug-associated toxicities, transmission of drug-resistant variants, and devel...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rawson JM,Roth ME,Xie J,Daly MB,Clouser CL,Landman SR,Reilly CS,Bonnac L,Kim B,Patterson SE,Mansky LM

    更新日期:2016-06-01 00:00:00

  • Downsizing of an HIV-cell fusion inhibitor, T22 ([Tyr5,12, Lys7]-polyphemusin II), with the maintenance of anti-HIV activity and solution structure.

    abstract::T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). T22, an 18-residue peptide amide, takes an antiparallel beta-sheet structure that is maintained by two disulfide bridges. Herein we synthesize...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tamamura H,Waki M,Imai M,Otaka A,Ibuka T,Waki K,Miyamoto K,Matsumoto A,Murakami T,Nakashima H,Yamamoto N,Fujii N

    更新日期:1998-04-01 00:00:00

  • Substituted pteridinones as p90 ribosomal S6 protein kinase (RSK) inhibitors: A structure-activity study.

    abstract::The activity of p90 ribosomal S6 kinase 2 (RSK2) has emerged as an attractive target for cancer therapy due to its role in the regulation of diverse cellular processes, such as cell transformation and proliferation. Several pan-RSK inhibitors have been identified with BI-D1870 and the pseudo-analogs LJH685 and LJI308 ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Casalvieri KA,Matheson CJ,Backos DS,Reigan P

    更新日期:2020-03-01 00:00:00

  • Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents.

    abstract::Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target, since inhibitors of this protease affect the pathology appropriately. By exploring the N-acylhydrazones (NAH) as privileged structures usually present in antiparasitic agents, we inv...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: dos Santos Filho JM,Leite AC,de Oliveira BG,Moreira DR,Lima MS,Soares MB,Leite LF

    更新日期:2009-09-15 00:00:00

  • Synthesis and evaluation of aryliden- and hetarylidenfuranone derivatives of usnic acid as highly potent Tdp1 inhibitors.

    abstract::Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for stalled DNA-topoisomerase 1 (Top 1) cleavage complexes and other 3'-end DNA lesions. Tdp1 is a promising target for anticancer therapy, since it can repair DNA lesions caused by Top1 inhibitors leading to drug resistance. Hence, Tdp1 inhibition should resul...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zakharova O,Luzina O,Zakharenko A,Sokolov D,Filimonov A,Dyrkheeva N,Chepanova A,Ilina E,Ilyina A,Klabenkova K,Chelobanov B,Stetsenko D,Zafar A,Eurtivong C,Reynisson J,Volcho K,Salakhutdinov N,Lavrik O

    更新日期:2018-08-15 00:00:00

  • Design and synthesis of novel androgen receptor antagonists with sterically bulky icosahedral carboranes.

    abstract::Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having remarkable chemical and thermal stability, and hydrophobic character. These features may allow application of carboranes as a new hydrophobic core structure in biologically active molecules that interact...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Goto T,Ohta K,Suzuki T,Ohta S,Endo Y

    更新日期:2005-12-01 00:00:00

  • Binding to delta and mu opioid receptors by deltorphin I/II analogues modified at the Phe3 and Asp4/Glu4 side chains: a report of 32 new analogues and a QSAR study.

    abstract::The synthesis and binding affinities of 32 X3Gly4 dual-substitution analogues of the natural opioid heptapeptides deltorphin I and II are reported. A multiple regression QSAR analysis was performed using those results along with literature data for the X3Asp4 and Phe3X4 side chain analogues. Fitting to a three-term po...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Schullery SE,Mohammedshah T,Makhlouf H,Marks EL,Wilenkin BS,Escobar S,Mousigian C,Heyl DL

    更新日期:1997-12-01 00:00:00

  • The evaluation of quinonoid compounds against Trypanosoma cruzi: synthesis of imidazolic anthraquinones, nor-beta-lapachone derivatives and beta-lapachone-based 1,2,3-triazoles.

    abstract::In continuing our screening program of naphthoquinone activity against Trypanosoma cruzi, the aetiological agent of Chagas' disease, new beta-lapachone-based 1,2,3-triazoles, 3-arylamino-nor-beta-lapachones, 3-alkoxy-nor-beta-lapachones and imidazole anthraquinones were synthesised and evaluated against bloodstream tr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: da Silva EN Jr,Guimarães TT,Menna-Barreto RF,Pinto Mdo C,de Simone CA,Pessoa C,Cavalcanti BC,Sabino JR,Andrade CK,Goulart MO,de Castro SL,Pinto AV

    更新日期:2010-05-01 00:00:00

  • Synthesis of functionalized 2-aryl-5-nitro-1H-indoles and their activity as bacterial NorA efflux pump inhibitors.

    abstract::In order to develop structure-activity relationships and to provide access to antibacterial agents for dual action studies, a variety of aryl group-substituted 2-aryl-5-nitro-1H-indoles were synthesized and the activity of the compounds assessed as inhibitors of the NorA multidrug resistance pump in the bacterium Stap...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Samosorn S,Bremner JB,Ball A,Lewis K

    更新日期:2006-02-01 00:00:00

  • Design, synthesis, and biological evaluation of amide imidazole derivatives as novel metabolic enzyme CYP26A1 inhibitors.

    abstract::All-trans-retinoic acid (ATRA) as a physiological metabolite of vitamin A is widely applied in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. CYP26A1 enzyme, induced by ATRA in liver and target tissues, metabolizes ATRA into 4-hydroxyl-RA. Inhibition of CYP26A1 metabolic enzyme represents a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sun B,Liu K,Han J,Zhao LY,Su X,Lin B,Zhao DM,Cheng MS

    更新日期:2015-10-15 00:00:00

  • Exploiting the human peptidome for novel antimicrobial and anticancer agents.

    abstract::Infectious diseases and cancers are leading causes of death and pose major challenges to public health. The human peptidome encompasses millions of compounds that display an enormous structural and functional diversity and represents an excellent source for the discovery of endogenous agents with antimicrobial and/or ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Bosso M,Ständker L,Kirchhoff F,Münch J

    更新日期:2018-06-01 00:00:00

  • Design, synthesis and herbicidal activity of new iron chelating motifs for HPPD-inhibitors.

    abstract::HPPD (p-hydroxyphenylpyruvate dioxygenase) is a herbicidal target that all major companies active in plant protection research have worked on intensely in the last decade. Several modern herbicides with this mode of action have been introduced recently, or are currently in development. The activity of all commercializ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Witschel M

    更新日期:2009-06-15 00:00:00

  • Synthesis and binding mode of heterocyclic analogues of suramin inhibiting the human basic fibroblast growth factor.

    abstract::The design, synthesis, and biological evaluation of a series of pyrrole and pyrazole congeners 2 of suramin, directed toward the development and identification of new ligands that complex the human fibroblast growth factor (bFGF), thereby inhibiting tumor-promoted angiogenesis, is reported. Compounds 2 were evaluated ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Manetti F,Cappello V,Botta M,Corelli F,Mongelli N,Biasoli G,Borgia AL,Ciomei M

    更新日期:1998-07-01 00:00:00

  • Ophiobolin M and analogues, noncompetitive inhibitors of ivermectin binding with nematocidal activity.

    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

    pub_type: 杂志文章


    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

  • Antifungal polyketide derivatives from the endophytic fungus Aplosporella javeedii.

    abstract::Six new polyketides aplojaveediins A-F (1-6) were isolated from the endophytic fungus Aplosporella javeedii associated with the host plant Orychophragmus violaceus (Brassicaceae). The structures of the new metabolites were elucidated by analysis of their NMR and MS data. Compound 1 exhibited antifungal activity agains...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gao Y,Wang L,Kalscheuer R,Liu Z,Proksch P

    更新日期:2020-05-15 00:00:00

  • High affinity central benzodiazepine receptor ligands. Part 3: insights into the pharmacophore and pattern recognition study of intrinsic activities of pyrazolo[4,3-c]quinolin-3-ones.

    abstract::Novel 2-phenyl-2,5-dihydropyrazolo[4,3-c]quinolin-3-(3H)-ones (PQs) endowed with high affinity for central benzodiazepine receptor (BzR) were synthesized. In particular, 9-fluoro-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (2(2)) showed binding affinity in the subnanomolar concentration range and p...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Carotti A,Altomare C,Savini L,Chiasserini L,Pellerano C,Mascia MP,Maciocco E,Busonero F,Mameli M,Biggio G,Sanna E

    更新日期:2003-11-17 00:00:00

  • The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics.

    abstract::This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rawson DJ,Ballard S,Barber C,Barker L,Beaumont K,Bunnage M,Cole S,Corless M,Denton S,Ellis D,Floc'h M,Foster L,Gosset J,Holmwood F,Lane C,Leahy D,Mathias J,Maw G,Million W,Poinsard C,Price J,Russel R,Street S

    更新日期:2012-01-01 00:00:00

  • New cannabinoid receptor antagonists as pharmacological tool.

    abstract::Synthesis and pharmacological evaluation of a new series of cannabinoid receptor antagonists of indazole ether derivatives have been performed. Pharmacological evaluation includes radioligand binding assays with [3H]-CP55940 for CB1 and CB2 receptors and functional activity for cannabinoid receptors on isolated tissue...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: González-Naranjo P,Pérez C,Girón R,Sánchez-Robles EM,Martín-Fontelles MI,Carrillo-López N,Martín-Vírgala J,Naves M,Campillo NE,Páez JA

    更新日期:2020-10-01 00:00:00

  • Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition.

    abstract::Human pancreatic cancer cells such as PANC-1 are known to exhibit marked tolerance to nutrition starvation that enables them to survive for prolonged period of time even under extremely nutrient-deprived conditions. Thus, elimination of this tolerance to nutrition starvation is regarded as a novel approach in anticanc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Awale S,Li F,Onozuka H,Esumi H,Tezuka Y,Kadota S

    更新日期:2008-01-01 00:00:00