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A series of amino alcohols have been prepared in a chemo-, diastereo- and enantioselective fashion starting from the corresponding (het)aryl diketones, avoiding tedious chemical protection and deprotection steps. Different alcohol dehydrogenases have been

Chiral fluorinated hydroxyketones were synthesized with excellent ee (>98%) and yield by a chemo- and stereoselective reduction of prochiral methyl/trifluoromethyl diketones using commercially available ketoreductase enzymes. By using p- and m-trifluoroac

Organotellurium compounds exhibit a broad range of useful applications in organic synthesis, materials science and medicinal chemistry fields. Despite their increasing applicability, the synthesis of enantiomerically pure organotellurium compounds remains nowadays scarcely reported in the literature. Herein, the chemical synthesis and biocatalyzed reductions of a set of telluro-acetophenones using both (R) and (S)-selective alcohol dehydrogenases (ADHs) is described for the first time, obtaining enantiomerically enriched hydroxy tellurides with excellent selectivities under very mild reaction conditions. On the one hand, enantiopure para-substituted (S)-hydroxy tellurides were obtained using the Ras-ADH (77–95 % conversion) and ADH-A (52–75 %), the ADH-A leading to the enantiopure (S)-hydroxy tellurides substituted at the meta-position (69–75 %). On the other hand, the evo-1.1.200 displayed high selectivity towards the preparation of optically alcohols with substitutions at the para-position of the aromatic ring (60–68 % conversion and 92–97 % ee), while the Lb-ADH led to the best results when reducing bulky ketones at the meta-position (79–82% conversion and 88–99 % ee).

The use of antioxidants is the most effective means to protect the organism against cellular damage caused by oxidative stress. In this context, organotellurides have been described as promising antioxidant agents for decades. Herein, a series of N-functionalized organotellurium compounds has been tested as antioxidant and presented remarkable activities by three different in vitro chemical assays. They were able to reduce DPPH[rad] radical with IC50 values ranging from 5.08 to 19.20 μg mL?1, and some of them also reduced ABTS[rad]+ radical and TPTZ-Fe3+ complex in ABTS[rad]+ and FRAP assays, respectively. Initial structure-activity relationship discloses that the nature of N-substituent strongly influenced both activity and cytotoxicity of the studied compounds. Furthermore, radical scavenging activities of N-functionalized organotellurides have been compared with those of their selenilated congeners, demonstrating that the presence of tellurium atom has an essential role in antioxidant activity.

Leishmaniasis is a neglected tropical disease and a public health concern in at least 98 countries, affecting mainly the poorest populations. Pharmaceuticals and chemotherapies available for leishmaniasis treatment have several limitations, which clearly justify the efforts to find new potential antileishmanial drugs. In this context, antiprotozoal activities toward different Leishmania species have been reported for hypervalent tellurium compounds, which motivated us to investigate, for the first time, the leishmanicidal properties of some nonhypervalent diaryl ditellurides. Thus, this work describes in vitro activity against Leishmania amazonensis and the cytotoxicities of diaryl ditellurides. Ditelluride LQ7 revealed a strong leishmanicidal activity on promastigotes and amastigotes at submicromolar levels (IC50 = 0.9 ± 0.1 and 0.5 ± 0.1 μmol L-1, respectively) and presented selectivity indexes greater than those of reference drug miltefosine. This preliminary study suggests that diaryl ditellurides may be promising scaffolds for the development of new agents for leishmaniasis treatment.

Organoselenium and organotellurium amines have been shown to present a broad range of interesting properties for both synthetic and biological applications. Despite the current interest in this class of compounds, only few methods to access organochalcogen amines are described in literature, most which involve restrictive conditions associated with displacement reaction, metal-assisted reactions or enzymatic approach. In general, these methods produce organochalcogen amines in poor yields, by long reactions that require protective groups. In this regard, a set of aryl chalcogen (Se, Te) amines were prepared by reductive amination employing a microwave-assisted one-pot protocol. This approach offered a convenient and versatile method to synthesize primary and secondary organochalcogen amines with significantly short time reactions (5–10 min) and satisfactory yields (40–89%).

Retinoic acid receptor (RAR)-related orphan receptors (RORs) regulate a variety of physiological processes, including hepatic gluconeogenesis, lipid metabolism, circadian rhythm and immune function. The RAR agonist: all-trans retinoic acid was reported to be an RORβ inverse agonist, but no information is available regarding ROR activity of its synthetic analogue Am580. Therefore, we screened Am580 and some related tetramethyltetrahydronaphthalene derivatives and carried out structural development studies, including substitution of carbon atoms with silicon, with the aim of creating a potent ROR transcriptional inhibitor. The phenyl amide disila compound 22 showed the most potent ROR-inhibitory activity among the compounds examined. Its activity towards RORα, RORβ and RORγ was increased compared to that of Am580. The IC50 values for RORα, RORβ and RORγ are 1.3, >10 and 4.5 μM, respectively.

The invention relates to oxazole and thiazole derivatives of formula (I), wherein A, E, X, R1 and R2 are as defined in the description, their preparation and their use as pharmaceutically active compounds.

The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-l-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit Kiapp ≥ 10 nM and GI50 ≈ 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.

The invention relates to oxazole and thiazole derivatives of formula (I), wherein A, E, X, R1 and R2 are as defined in the description, their preparation and their use as pharmaceutically active compounds.

The invention relates to aminotriazole derivatives of formula (I), wherein A, E, R1 and R2 are as defined in the description, their preparation and their use as pharmaceutically active compounds. The compounds are useful for the prevention or treatment of diseases, which respond to the modulation of the ALX receptor such as inflammatory diseases.

Several synthetic strategies to diamines 1-3 are described. The optimum approach via opening of aziridine afforded 1-3 in 29-60% yield over 3-5 steps. A study on formation of the benzylic stereocenter using Toste's rhenium-catalyzed asymmetric reduction of phosphinyl ketimines was also evaluated and afforded 15 in 92% de.

Tris[3-(3-dimethylamino-1-oxoprop-2-enyl)phenyl]phosphane oxide, which can be synthesized quantitatively by oxidation of the corresponding phosphane, crystallizes in the trigonal space group R3. Because of the four different strong proton accepting sites

The invention relates to a method for producing substituted phosphanes as well as substituted phosphanes produced according to said method. The aim of the invention is to use phosphanes, phosphane oxides, phosphane sulfides, or phosphane selenides, which

Novel triphenyl phosphine ligands bearing pyrazole or 2-aminopyrimidine groups in the ortho or meta position of one or three of the phenyl rings were obtained starting from the corresponding acyl derivatives Ph2P(o- C6H4-C

The present invention is directed to novel diaminothiazoles of formula These compounds inhibit cyclin-dependent kinase 4 (Cdk4) and are selective against Cdk2 and Cdk1. These compounds and their pharmaceutically acceptable salts and esters have antiproliferative activity and are useful in the treatment or control of cancer, in particular solid tumors. This invention is also directed to pharmaceutical compositions containing such compounds and to methods of treating or controlling cancer, most particularly the treatment 6r control of breast, lung and colon and prostate tumors.

The invention concerns novel bi-aromatic compounds having the formula: which are analogs of vitamin D, the process of preparing them, as well as their use in pharmaceutical compositions in human or veterinary medicine, particularly in dermatology, cancer treatment, treatment of auto-immune diseases, and in organ or tissue transplants. Cosmetic compositions and methods of use are also included.

A series of organochalcogeno acetophenones 3 has been submitted to the action of enzymes from Daucus carota root. Some of the chalcogeno ketones tested afforded the chiral organochalcogeno-α-methylbenzyl alcohols 4 in excellent enantiomeric excesses (>99%), under mild and environmentally friendly conditions. The stereoselectivity of the reduction is in accordance with Prelog's rule. Enzymatic kinetic resolution as alternative process was used to obtain the chiral ortho-organochalcogeno-α-methylbenzyl alcohols in excellent enantiomeric excess (>99%).

Compounds of Formula (I) wherein R1, R2 R3, R4, R5, R6, and X are as defiend herein for Formula (IA) and Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocoricoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

Compounds of formula (I) are hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors, and are useful in therapeutic and prophylactic treatment of persons infected with hepatitis C virus.

PCT No. PCT/US96/06533 Sec. 371 Date Nov. 13, 1997 Sec. 102(e) Date Nov. 13, 1997 PCT Filed May 8, 1996 PCT Pub. No. WO96/36633 PCT Pub. Date Nov. 21, 1996Compounds of Formula I, and their N-oxides and agriculturally suitable salts, are disclosed which ar

The synthesis and biological evaluation of oximes of 2-aryl-6-methoxy-3,4-dihydronaphthalene (7a, 7b, 14a, 14b) as nonsteroidal inhibitors of 17α-hydroxylase-C17,20-lyase (P450 17, CYP 17) is described. The target compounds were synthesized and identified

(S)-2-[4′-(2″-Methylpropyl)phenylpropanoic acid (ibuprofen) and (S)-2-(3′-benzoylphenyl)propanoic acid (ketoprofen) have been synthesised in high enantiomeric excess. Control of stereochemistry was achieved by a combination of Sharpless epoxidalion followed by catalytic hydrogenolysis of the introduced benzylic epoxide oxygen bond. Also, the coupling of organic compounds in the presence of palladium with enantiopure 2-(3-iodophenyl)propanoic and 2-(4-iodophenyl)propanoic acids, prepared by the methodology above, is a general method for the synthesis of optically active arylpropanoic acids.

The retinoidal activities of trimethylsilyl or trimethylgermyl-containing retinobenzoic acids are discussed on the basis of differentiation-inducing activity on human promyelocytic leukemia cells HL-60.Compounds with a trimethylsilyl or trimethylgermyl gr

The design and 30-step synthesis of a transacylase mimic is described.The target catalyst combines a macrocyclic binding site, a hydroxymethyl goup, and an imidazole group organized to act cooperatively through their attachment to a quaterphenyl support s