- A COMPOUND FOR THE DETERMINATION OF THE PROTEIN FKBP12 AND A SENSOR UNIT COMPRISING IT
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The present invention relates to novel compounds useful as sensors for the rapid and specific determination of the FKBP12 protein, a peptidyl-prolyl cis-trans isomerase (PPlase), the levels of which in the biological fluids of a subject change if the subject is affected by pathological conditions, in particular neurodegenerative diseases, such as the Parkinson's disease and the Alzheimer's syndrome, tumour pathologies, autoimmune diseases, or if that subject is in a phase of acute rejection after organ transplantation.
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Page/Page column 19; 21
(2021/06/26)
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- APOPTOSIS-INDUCING AGENTS
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Provided are certain Bcl-2 inhibitors, pharmaceutical compositions thereof, and methods of use thereof.
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Paragraph 295; 296
(2018/11/22)
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- Stereoselective total synthesis of (+)-radicamine B via anti,syn,syn-oxazine
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The stereoselective total synthesis of (+)-radicamine B was achieved using commercially available D-4-hydroxy-phenylglycine via chiral 1,3-oxazine, which has been applied to synthesis of amino polyols such as DAB-1, D-fagomine, and phytosphingosines. The key steps in this strategy were the palladium(0)-catalyzed stereoselective intramolecular oxazine formation, an extension of the chirality of anti,syn-oxazine with Lewis acid and vinylmagnesium bromide, and pyrrolidine ring formation via hydrogenation reaction. The chiral extension is also applicable to other chiral 1,3-oxazine derived from D-4-hydroxy-phenylglycine.
- Kim, Jin-Seok,Kim, Gun-Woo,Kang, Jong-Cheol,Myeong, In-Soo,Jung, Changyoung,Lee, Yong-Taek,Choo, Gyung-Ho,Park, Seok-Hwi,Lee, Gyu-Jin,Ham, Won-Hun
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p. 171 - 176
(2019/05/10)
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- Copper(II)-catalyzed enantioselective intramolecular cyclization of N-alkenylureas
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The first Cu(II)-catalyzed highly enantioselective intramolecular cyclization of N-alkenylureas was developed for the concise assembly of chiral vicinal diamino bicyclic heterocycles. Facile removal of carbonyl group of the carbamido moiety allowed for ready access to enantioenriched cyclic vicinal diamines.
- Fu, Shaomin,Yang, Honghao,Deng, Yuanfu,Jiang, Huanfeng,Zeng, Wei,Li, Guoqiang
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supporting information
p. 1018 - 1021
(2015/03/30)
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- HETEROCYCLIC COMPOUNDS AS JANUS KINASE INHIBITORS
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The invention provides compounds of formula I: (I) or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing com-pounds of formula I, intermediates useful for preparing com-pounds of formula I and therapeutic methods for suppressing an immune response or treating cancer, including a hematologic malignancy, using compounds of formula I
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Page/Page column 137; 138
(2013/03/28)
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- GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention provides gonadotropin releasing hormone receptor antagonists and the pharmaceutical composition comprising the same, which can be useful in preventing or treating a sex hormone-related disease such as endometriosis, amenorrhea, irregular menstruation, uterine myoma, uterine fibroids, polycystic ovarian disease, lupus erythematous, hypertrichosis, precocious puberty, short stature, acne, alopecia, gonadal steroid-dependent neoplasms, gonadotropin-producing pituitary adenoma, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hyperplasia, contraception, and infertility, as well as Alzheimer disease
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Page/Page column 74
(2013/09/12)
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- Preparation of α-amino acids by oxidative oxazoline-oxazinone rearrangement-hydrogenation (OOOH). Scope and limitations
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The range and scope of the oxidative oxazoline-oxazinone rearrangement-hydrogenation sequence (OOOH)-a short, direct asymmetric synthesis of α-amino acids from carboxylic acids-was explored. The highest yet reported diastereoselectivity for hydrogenation of the oxazinone C=N bond (d.r.=>80:1) is disclosed and rationalized with the aid of ab initio molecular calculations.
- Liu, Chaomin,Molinski, Tadeusz F.
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p. 2022 - 2027
(2011/11/29)
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- PROCESS FOR THE SYNTHESIS OF HYDROXYPHENYLGLYCINE ESTERS
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The present invention refers to a process for the synthesis of a D-(-)-p-hydroxyphenylglycine (HPG) ester in crystal form, by crystallizing D-HPG ester from a solution containing dissolved D-HPG ester to obtain a suspension comprising D-HPG ester crystals, characterized in that the eeD of the D-HPG ester in the solution and the eeD of the D-HPG ester crystals is above 95%, preferably above 97%, more preferably above 98%, more preferably above 99%, more preferably above 99.5%.
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Page/Page column 7-9
(2011/10/10)
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- 5-LIPOXYGENASE INHIBITORS
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The present invention relates to pyrazole derivatives and to processes for their synthesis as 5 -lipoxygenase (5-LO) inhibitors. The present invention also relates to pharmacological compositions containing these pyrazole derivatives, as well as methods of treating bronchial asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, multiple sclerosis, Type I diabetes, psoriasis, allograft rejection, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, cancer, pruritis, allergic rhinitis and other inflammatory and/or autoimmune disorders.
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Page/Page column 23
(2012/01/13)
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- Novel 2-[(benzylamino)methyl]pyrrolidine-3,4-diol derivatives as α-mannosidase inhibitors and with antitumor activities against hematological and solid malignancies
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Novel α-mannosidase inhibitors of the type (2R,3R,4S)-2-({[(1R)-2-hydroxy-1-arylethyl]amino}methyl)pyrrolidine-3,4-diol have been prepared and assayed for their anticancer activities. Compound 30 with the aryl group = 4-trifluoromethylbiphenyl inhibits the proliferation of primary cells and cell lines of different origins, irrespective of Bcl-2 expression levels, inducing a G2/Mcell cycle arrest and by modification of genes involved in cell cycle progression and survival.
- Bello, Claudia,Cea, Michele,Bello, Giovanna Dal,Garuti, Anna,Rocco, Ilaria,Cirmena, Gabriella,Moran, Eva,Nahimana, Aimable,Duchosal, Michel A.,Fruscione, Floriana,Pronzato, Paolo,Grossi, Francesco,Patrone, Franco,Ballestrero, Alberto,Dupuis, Marc,Sordat, Bernard,Nencioni, Alessio,Vogel, Pierre
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experimental part
p. 3320 - 3334
(2010/07/05)
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- Using ionic liquid [EMIM][CH3COO] as an enzyme-'friendly' co-solvent for resolution of amino acids
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An ionic liquid (IL), 1-ethyl-3-methylimidazolium acetate [EMIM][CH3COO], was used in 0-4.0 M (～60% IL, v/v), as a nonvolatile organic medium for the enzymatic resolution of amino acids. When dl-phenylalanine methyl ester was studied as a model substrate, high enantiomeric excesses (ee) of l-amino acid were obtained in all ionic concentrations; however, lower yields were observed at high IL concentrations. This IL is more enzyme-'friendly' than the hydrophilic organic solvent acetonitrile and those ILs containing chaotropic anions (such as [EMIM][OTs]). Among three proteases and two lipases investigated, lyophilized Bacillus licheniformis protease exhibited the best enantioselectivity and activity. Highly enantioselective resolutions were also produced for several other amino acids in 2.0 M IL. Interestingly, high ee were also found in deuterium oxide (D2O) rather than in ordinary water, and a further enhancement was achieved with the co-existence of [EMIM][CH3COO]. The heavy water effect was explained in terms of protein stabilization by D2O. The secondary structural changes of enzyme in various media were interpreted by the second derivatives of FT-IR spectra.
- Zhao, Hua,Jackson, Lee,Song, Zhiyan,Olubajo, Olarongbe
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p. 2491 - 2498
(2007/10/03)
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- A Reactivity/Affinity Switch for Parallel Kinetic Resolution: α-Amino Acid Quasienantiomers and the Resolution of Cyclopropene Carboxylic Acids
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A new type of parallel kinetic resolution (PKR) is reported in which quasienantiomers with very similar reactivities give products whose chromatographic properties diverge upon the addition of fluoride. This concept of a reactivity/affinity switch is applied to the PKR of cyclopropene carboxylic acids with all-carbon quaternary centers. This is the first application of α-amino acid quasienantiomers in PKR, and it is a complementary approach for acyltransfer systems where the asymmetry is induced by the nucleophile rather than the leaving group. Excellent diastereoselectivities (ranging from 90:10 to 99.5:5) and good yields were obtained for both quasienantiomeric products, and the reactions can be run on significant scale because the separation is trivial. High-level DFT calculations (B3LYP functional with the 6-31+G(d,p) basis set) provided transition-state structures with relative energies that are in accord with the experimental observations. Copyright
- Liao, Lian-An,Zhang, Fan,Dmitrenko, Olga,Bach, Robert D.,Fox, Joseph M.
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p. 4490 - 4491
(2007/10/03)
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- The anandamide membrane transporter. Structurea€"activity relationships of anandamide and oleoylethanolamine analogs with phenyl rings in the polar head group region
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A new series of arachidonic and oleic acids derivatives, most of which with aromatic moieties in the head group region, has been synthesized and evaluated as inhibitors of anandamide uptake. A new series of anandamide and N-oleoylethanolamine analogs, most of which with aromatic moieties in the head group region, has been synthesized and evaluated as inhibitors of anandamide uptake. Some of them efficaciously inhibit the uptake process with Ki values in the low micromolar range (2.4-21.2 μM). Strict structural requisites are needed to observe a significant inhibition and in no case inhibition of fatty acid amidohydrolase overlaps with inhibition of anandamide uptake.
- Di Marzo, Vincenzo,Ligresti, Alessia,Morera, Enrico,Nalli, Marianna,Ortar, Giorgio
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p. 5161 - 5169
(2007/10/03)
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- ACETYLENIC ALPHA-AMINO ACID-BASED SULFONAMIDE HYDROXAMIC ACID TACE INHIBITORS
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Compound of the formula (B) are useful in treating disease conditions mediated by TNF- alpha , such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.
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- Divalent and trivalent α-ketocarboxylic acids as inhibitors of protein tyrosine phosphatases
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Protein tyrosine phosphatases (PTPases) are important targets for the treatment of insulin resistance in patients with type II diabetes and as antibacterial agents. As a result, there is a growing interest in the development of potent and specific inhibitors for these enzymes. This paper describes a series of inhibitors that contain two or three α-ketocarboxylic acid groups that are designed to form multiple contacts with residues inside or near the active site of phosphatases. The inhibitors have been assayed against three PTPases: the Yersinia PTPase, PTP1B, and LAR. The best of the inhibitors has IC50 values against the Yersinia PTPase and PTP1B of 0.7 and 2.7 μM, respectively. These divalent and trivalent compounds are significantly more potent than their corresponding monovalent analogues. In addition, they show good selectivity for PTP1B and the Yersinia PTPase as compared to LAR.
- Chen, Yen Ting,Seto, Christopher T.
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p. 3946 - 3952
(2007/10/03)
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- D-Phenylglycine and D-4-hydroxyphenylglycine methyl esters via penicillin G acylase catalysed resolution in organic solvents
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Penicillin G acylase in organic solvents catalyses specifically the acylation of the L-enantiomers of methyl esters of phenylglycine and 4- hydroxyphenylglycine. Hydrolytic reactions are prevented by controlling the water activity of the system and no excess of acylating agent is required. The process leads to the facile isolation of the enantiomerically pure D- enantiomer, which is of practical use for the preparation of β-lactam antibiotics. Electrospray mass spectroscopy has been applied to the study of the enantioselectivity of the enzyme. (C) 2000 Elsevier Science Ltd.
- Basso, Alessandra,Braiuca, Paolo,De Martin, Luigi,Ebert, Cynthia,Gardossi, Lucia,Linda, Paolo
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p. 1789 - 1796
(2007/10/03)
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- Asymmetric synthesis of actinoidic acid derivatives
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(equation presented) Synthesis of fully protected actinoidic acid derivative 3 and selectively protected biaryl bisamino acid 4, intermediates for vancomycin total synthesis, are reported.
- Boisnard, Sabine,Neuville, Luc,Bois-Choussy, Michele,Zhu, Jieping
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p. 2459 - 2462
(2007/10/03)
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- Total synthesis of vancomycin - Part 2: Retrosynthetic analysis, synthesis of amino acid building blocks and strategy evaluations
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Retrosynthetic analysis of vancomycin (1) defined vancomycin's aglycon (2) and protected triazene 3 (Figure 1) as advanced intermediates for an eventual total synthesis. Sequential assembly of 3 as shown in Figure 2 (strategy I) and Figure 3 (strategy II) led to amino acid building blocks 8-10 and 12-15, respectively, representing vancomycin's amino acids AA-1 to AA-7. These amino acid fragments were constructed by stereoselective routes and the two synthetic strategies were tested for feasibility. Strategy I, postulating construction of the vancomycin main framework in the order of D-O-E→D-O-E/C-O-D→D-O-E/C-O-D/A-B, suffered from serious epimerization problems at the AA-4 stereocenter; while strategy II, involving the sequence C-O-D→C-O-D/AB→C-O-D/AB/D-O-E proved viable. These findings set the stage for the final drive towards vancomycin's aglycon (2) and vancomycin (1).
- Nicolaou,Boddy, Christopher N. C.,Li, Hui,Koumbis, Alexandros E.,Hughes, Robert,Natarajan, Swaminathan,Jain, Nareshkumar F.,Ramanjulu, Joshi M.,Braese, Stefan,Solomon, Michael E.
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p. 2602 - 2621
(2007/10/03)
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