- Asymmetric Michael reaction promoted by chiral thiazolidine-thiourea catalyst
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In this work, we report the synthesis and characterization of three new thiazolidine- and thiourea-based chiral organocatalysts. These compounds were successfully applied in asymmetric Michael addition reactions between different ketones and nitrostyrenes leading to products in up to 85% yield, >96:4 r.d. and 97% e.e. Computational studies were used to better visualize the proposed transition state and explain the observed stereoselectivities. One of the new catalysts was also successfully applied in an aldol addition between cyclohexanone an p-nitrobenzaldehyde leading to product in 80% yield, >96:4 d.r. and 80% e.e.
- da Silva, Tiago Lima,Rambo, Raoni Scheibler,Jacoby, Caroline Gross,Schneider, Paulo Henrique
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supporting information
(2019/12/27)
-
- Method for preparing thiazole-4-formic acid
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The invention discloses a method for preparing thiazole-4-formic acid. By the aid of the method, the problems of relatively high prices of raw materials used in old processes for thiabendazole which is one of important traditional pesticide and bactericide varieties and low yield of the thiabendazole can be solved. The method includes steps of generating thiazolidine-4-formic acid from L-cysteinehydrochloride, formaldehyde and pyridine; carrying out reaction on the thiazolidine-4-formic acid, methyl alcohol and HCl gas to generate thiazolidine-4-methyl formate; carrying out reaction on the thiazolidine-4-methyl formate, acetonitrile and MnO2 to generate thiazole-4-methyl formate; hydrolyzing the thiazole-4-methyl formate under the effect of sodium hydroxide to obtain the thiazole-4-formicacid which is a product. The method has the advantages of simple process synthetic route, mild reaction condition, low cost, environmental protection, safety, excellent application prospect, good social benefit and high economic benefit.
- -
-
Paragraph 0021-0023; 0031-0033; 0041-0043; 0051-0053
(2019/04/17)
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- Industrialized scale preparation method for pidotimod
-
The invention discloses an industrialized scale preparation method for pidotimod, and belongs to the technical field of medicine synthesis. The industrialized scale preparation method comprises the following steps of performing ring closure and esterification on L-cysteine, so as to obtain L-thiazolidine-carboxylic ester; then, condensing with L-pyroglutamic acid under the action of a condensing agent; then, performing ester hydrolysis, and crystallizing, so as to obtain a product meeting the medicinal standard. The industrialized scale preparation method has the advantages that the intermediate, such as L-thiazolidine-carboxylic ester hydrochloride, is not separated, the water is removed by a co-boiling method in the condensing reaction process, and the separating and drying steps of theintermediate are omitted; compared with other preparation methods, the technology is optimized, so as to shorten the large-scale production time, improve the yield rate, and reduce the production cost; the operability in the scale production of the pidotimod is realized.
- -
-
Paragraph 0018; 0020; 0022; 0024; 0026
(2018/11/03)
-
- X-ray crystal structures and anti-breast cancer property of 3-tert -butoxycarbonyl-2-arylthiazolidine-4-carboxylic acids
-
Diastereomeric '2RS,4R'-2-arylthiazolidine-4-carboxylic acids (ATCAs) were synthesized and their resolution to chiraly pure N-BOC derivatives was attempted by column chromatography. The absolute stereochemistry of the resolved compounds was ascertained by X-ray single crystal structures. Further application of the synthesized compounds was studied for their in vitro anti-breast cancer activity against MCF7 cell line using DOX as a standard by MTT assay method. Cell morphology analysis was carried out by fluorescence microscopy. The compounds containing '2S' absolute configuration in thiazolidine ring and presence of 2-NO2, 2,6-Cl groups on '2R'-aryl substituent showed significant anti-breast cancer activity where some of the compounds were found to be more active than DOX in terms of induced apoptosis mode of MCF7 cell death.
- Jagtap, Rohidas M.,Thorat, Shridhar H.,Gonnade, Rajesh G.,Khan, Ayesha A.,Pardeshi, Satish K.
-
p. 1078 - 1086
(2018/02/06)
-
- New aspects of the formation of 2-substituted thiazolidine-4-carboxylic acids and their thiohydantoin derivatives
-
Aromatic aldehydes reacted readily with (R)-cysteine in boiling acidified methanol to give diastereomeric mixtures of the corresponding 2-(aryl substituted) thiazolidine-4-carboxylic acids. 4-Nitrobenzaldehyde under similar conditions afforded one isomer of 2-(4-nitrophenyl)-thiazolidine-4-carboxylic acid, which epimerized in the NMR solvents into a diastereomeric mixture. 2-Nitrobenzaldehyde reacted with (R)-cysteine to afford 3,5-bis-(2-nitrophenyl)-tetrahydro-1H-thiazolo[3,4-c]oxazol-1-one as the sole product, which collapsed in the NMR solvent into a diastereomeric mixture of the thiazolidine-4-carboxylic acids. The thiazolidine derivatives reacted smoothly with phenyl isothiocyanate to give single isomers of the corresponding thiohydantoins.
- Mahdy, Ahmed R.E.,Elboray, Elghareeb E.,Fandy, Ragab F.,Abbas-Temirek, Hussien H,Aly, Moustafa F.
-
p. 105 - 121
(2018/05/14)
-
- Small molecule diselenide additives for in vitro oxidative protein folding
-
The in vitro oxidative folding of disulfide-rich proteins can be challenging. Here we show a new class of small molecule diselenides, which can be easily prepared from inexpensive starting materials, used to enhance oxidative protein folding. These compounds were tested on a model protein, bovine pancreatic trypsin inhibitor. Two of the tested diselenides showed considerable improvement over glutathione and were on par with the previously described selenoglutathione.
- Reddy, Post Sai,Metanis, Norman
-
supporting information
p. 3336 - 3339
(2016/02/27)
-
- Carbon-sulfur bond-forming reaction catalysed by the radical SAM enzyme HydE
-
Carbon-sulfur bond formation at aliphatic positions is a challenging reaction that is performed efficiently by radical S-adenosyl-L-methionine (SAM) enzymes. Here we report that 1,3-thiazolidines can act as ligands and substrates for the radical SAM enzyme HydE, which is involved in the assembly of the active site of [FeFe]-hydrogenase. Using X-ray crystallography, in vitro assays and NMR spectroscopy we identified a radical-based reaction mechanism that is best described as the formation of a C-centred radical that concomitantly attacks the sulfur atom of a thioether. To the best of our knowledge, this is the first example of a radical SAM enzyme that reacts directly on a sulfur atom instead of abstracting a hydrogen atom. Using theoretical calculations based on our high-resolution structures we followed the evolution of the electronic structure from SAM through to the formation of S-adenosyl-L-cysteine. Our results suggest that, at least in this case, the widely proposed and highly reactive 5′-deoxyadenosyl radical species that triggers the reaction in radical SAM enzymes is not an isolable intermediate.
- Rohac, Roman,Amara, Patricia,Benjdia, Alhosna,Martin, Lydie,Ruffié, Pauline,Favier, Adrien,Berteau, Olivier,Mouesca, Jean-Marie,Fontecilla-Camps, Juan C.,Nicolet, Yvain
-
p. 491 - 500
(2016/05/09)
-
- Thiazolidine esters: New potent urease inhibitors
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A variety of esters of thiazolidine-4-caboxylic acid were synthesized and investigated for their urease inhibitory properties. A significant increase in urease inhibitory activities of these ester derivatives has been observed. The order of activity increases from methyl ester to heptyl ester but further prolongation of the alkyl chain was proved to be detrimental for receptor binding. These findings provide evidence that the nature of the alkyl chain has a significant impact on the coordination of thiazolidine esters with bi-metallic nickel center of urease. It was also observed that inhibition potentiated by lower pH and with increase in time.
- Lodhi, Muhammad Arif,Shams, Sulaiman,Khan, Khalid Mohammad
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p. 858 - 864
(2015/01/30)
-
- A highly enantio- and diastereoselective direct aldol reaction in aqueous medium catalyzed by thiazolidine-based compounds
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Taking l-aminoacids as starting materials, a new set of enantiopure thiazolidine-based organocatalysts were prepared using a simple synthetic approach and successfully applied in the asymmetric direct aldol reaction between various cyclic ketones and aldehydes in a saturated aqueous medium. The aldol adducts were obtained with excellent enantioselectivity (up to >99% ee) and diastereoselectivity (dr >20:1).
- Rambo, Raoní Scheibler,Gross Jacoby, Caroline,Da Silva, Tiago Lima,Schneider, Paulo Henrique
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p. 632 - 637
(2015/08/03)
-
- PROCESS FOR PURIFYING (METH)ACRYLIC ACID
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A process for producing a grade of (meth)acrylic acid having residual formaldehyde levels of under 100 parts per million.
- -
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Page/Page column 7-8
(2014/10/03)
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- Design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies
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The present study describes the synthesis of a series of new 4-aminoquinoline-derived thiazolidines and evaluation of their antimalarial activity against a NF-54 strain of Plasmodium falciparum in vitro and N-67 strain of Plasmodium yoelii in vivo. Among the series, two compounds, 2-(4-chloro-phenyl)-thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4- ylamino)-ethyl]-amide hydrochloride (14) and 2-(2,6-dichloro-phenyl)- thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4-ylamino)-ethyl]-amide hydrochloride (22) exhibited significant suppression of parasitaemia in the in vivo assay. All the analogues were found to form strong complex with haematin and inhibited the β-haematin formation in vitro. These results suggest that these compounds act on heme polymerization target.
- Solomon, V. Raja,Haq,Srivastava, Kumkum,Puri, Sunil K.,Katti
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p. 619 - 626
(2013/05/09)
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- Inhibitors of an essential mycobacterial cell wall lipase (Rv3802c) as tuberculosis drug leads
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The first targeted inhibitors of an essential M. tuberculosis cell wall lipase, Rv3802c, are described. Lead compounds exhibited nanomolar inhibition of the enzyme, and encouraging antibacterial activity against M. tuberculosis in vitro, supporting Rv3802c as a novel TB drug target.
- West, Nicholas P.,Cergol, Katie M.,Xue, Millie,Randall, Elizabeth J.,Britton, Warwick J.,Payne, Richard J.
-
supporting information; experimental part
p. 5166 - 5168
(2011/06/10)
-
- Synthesis and biological activity of novel L-amino acid based analgesic compounds
-
Synthesis and analgesic activity studies of a series of L-amino acid based compounds were described. These compounds were designed as potential N-type Calcium Channel Blockers and their structures were confirmed by 1H NMR and ESI-MS spectra. Some of the compounds exhibited significant analgesic activity in Mouse Hot-Plate tests. According to the data of pharmacological experiments, we carried out preliminary structure-activity studies and the results indicated that this kind of compounds was useful for the development of new analgesic drugs.
- Pan, Junzhu,Wang, Qianqian,He, Gu,Ouyang, Liang,Guo, Li
-
scheme or table
p. 359 - 364
(2011/10/31)
-
- Spectroscopic and theoretical investigation of the conformational space of a pyrazolo-thiazole precursor of extended dipole diazafulvenium methide intermediates
-
The structure, preferred conformers and vibrational spectra of the pyrazolo-thiazole precursor of extended dipole diazafulvenium methide intermediates, dimethyl 2,2-dioxo-1H,3H-pyrazolo[1,5-c][1,3]thiazole-6,7-dicarboxylate (DPTD) were investigated in low-temperature noble gas matrices (Ar, Xe), low temperature neat amorphous and crystalline phases and in KBr pellet (crystal and melted phases) by infrared spectroscopy, supported by quantum chemical calculations. Two types of conformers were observed spectroscopically in the matrices and in the neat amorphous solid resulting from fast condensation of the vapour of the compound onto the cold (20 K) substrate of the cryostat. These conformers correspond to the two pairs of nearly degenerated structures exhibiting skew/cis (conformers S′C and SC′) and gauche/trans (conformers G′T and GT′) arrangements of the N{double bond, long}C-C{double bond, long}O/C{double bond, long}C-C{double bond, long}O moieties. In the crystalline phase, the vibrational signature of the compound indicates that it exists in a skew/cis arrangement. After melting of the crystal, a conformational mixture is formed, where both skew/cis and gauche/trans forms exist in equilibrium and, with all probability, also conformer G′C′. This latter conformer cannot exist in the low temperature matrices and amorphous state, in view of the very low energy barrier that separates this form from the lower energy SC′ conformer, which can be easily surpassed during deposition of the compound (conformational cooling).
- Nunes, Cláudio M.,Lopes, Susy,Pinho e Melo, Teresa M.V.D.,Fausto, Rui
-
body text
p. 101 - 108
(2009/08/15)
-
- Highly efficient small organic molecules for enantioselective direct aldol reaction in organic and aqueous media
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(Chemical Equation Presented) A series of highly efficient organocatalysts have been derived from naturally available amino acids for carrying out enantioselective direct aldol reaction in both organic and aqueous medium. The aldol products were obtained in high diastereoselectivities (up to 99:1) and enantioselectivities (up to >99% ee) for a broader range of substrates using 1 mol % of a catalyst. The results demonstrate that the structural features of organocatalysts play a crucial role in obtaining high optical purity of aldol adducts in an aqueous medium. Further, the role of water in increasing the rate and enantioselectivity of the reaction has been illustrated. Moreover, the aldol products have been employed in the synthesis of chiral amino alcohols which act as useful intermediates for building up complex natural products.
- Vishnumaya, Monika Raj,Singh, Vinod K.
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experimental part
p. 4289 - 4297
(2009/09/08)
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- EFFICIENT SYNTHESIS OF CHELATORS FOR NUCLEAR IMAGING AND RADIOTHERAPY: COMPOSITIONS AND APPLICATIONS
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Novel methods of synthesis of chelator-targeting ligand conjugates, compositions comprising such conjugates, and therapeutic and diagnostic applications of such conjugates are disclosed. The compositions include chelator-targeting ligand conjugates optionally chelated to one or more metal ions. Methods of synthesizing these compositions in high purity are also presented. Also disclosed are methods of imaging, treating and diagnosing disease in a subject using these novel compositions, such as methods of imaging a tumor within a subject and methods of diagnosing myocardial ischemia.
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Page/Page column 95-96
(2008/06/13)
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- HETEROCYCLIC CARBOXYLIC ACID DERIVATIVES AND PHARMACEUTICAL COMPOSITION FOR INHIBITING LIPID ACCUMULATION CONTAINING SAME
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The present invention relates to a novel heterocyclic carboxylic acid derivative, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same as an active ingredient for inhibiting the accumulation of lipids in the body.
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Page/Page column 54
(2008/12/04)
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- NOVEL DIPEPTIDYL PEPTIDASE INHIBITORS AND PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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The present invention relates to novel compounds representated by formula (I), where R, R1, R2, R3, X, Y, m, n are as defined.The present invention relates to compounds of the general formula I their derivatives, their analogs, their tautomeric forms, their stereoisomers, their diastereomers, their bioisosteres, their polymorphs, their pharmaceutically acceptable salts and pharmaceutically acceptable compositions containing them which are predominantly dipeptidyl peptidase IV inhibitors. The present invention also relates to the processes for the preparation of novel compounds of formula (I) and their use in treating type II diabetes and diabetic complications thereof and also for treating dislipidemia, hypercholesterolemia, obesity and hyperglycemia.
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Page/Page column 64-65
(2008/06/13)
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- NOVEL DIPEPTIDYL PEPTIDASE IV INHIBITORS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND PROCESS FOR THEIR PREPARATION
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The present invention relates to novel compounds useful as dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula: (I) wherein Y is -S(O)m, -CH2-, CHF, or -CF2; m is 0, 1, or 2; X is a bond, C1-C5 alkyl (e.g., -CH2-), or -C(=0)-; the dotted line [----] in the carbocyclic ring represents an optional double bond; R1 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl, CN, -COOR3, CONR3R4, -OR3, -NR3R4, or NR3COR3; R2 is hydrogen, cyano, COOH, or an isostere of a carboxylic acid (such as SO3H, CONOH, B(OH)2, PO3R3R4, SO2NR3R4, tetrazole, -COOR3, -CONR3R4, NR3COR4, or -COOCOR3).
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Page/Page column 45
(2008/06/13)
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- NEW ADAMANTANE DERIVATIVES AS DIPEPTIDYL, PEPTIDASE IV INHIBITORS, PROCESSES FOR THEIR PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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The present invention relates to dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula (A): wherein R1, R2, Y, and n are as defined herein, pharmaceutical compositions containing the same, processes for their preparation, and methods for treating disorders mediated by DPP-IV inhibition, such as diabetes, especially Type II diabetes, with them.
- -
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Page/Page column 30
(2008/06/13)
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- NOVEL DIPEPTIDYL PEPTIDASE IV INHIBITORS; PROCESSES FOR THEIR PREPARATION AND COMPOSITIONS THEREOF
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The present invention relates to novel dipeptidyl peptidase IV (DPP-IV) inhibitors or general formula (1) useful for treating diabetes, non-insulin dependent diabetes mellitus, impaired glucose tolerance, inflammatory bowel disease, ulcerative colitis,Chron’s disease, obesity, and metabolic syndrome.
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Page/Page column 37
(2008/06/13)
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- NEW DIPEPTIDYL PEPTIDASE IN INHIBITORS; PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING THEM
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The present invention relates to new dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula (I), and their analogs, isomers, pharmaceutical compositions and therapeutic uses, methods of making the same.
- -
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Page/Page column 40
(2010/02/12)
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- Synthesis of proline-modified analogues of the neuroprotective agent glycyl-L-prolyl-glutamic acid (GPE)
-
The synthesis of ten proline-modified analogues of the neuroprotective tripeptide GPE is described. Five of the analogues incorporate a proline residue with a hydrophobic group at C-2 and two further analogues have this side chain locked into a spirolactam ring system. The pyrrolidine ring was also modified by replacing the γ-CH2 group with sulfur and/or incorporation of two methyl groups at C-5.
- Harris, Paul W.R.,Brimble, Margaret A.,Muir, Victoria J.,Lai, Michelle Y.H.,Trotter, Nicholas S.,Callis, David J.
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p. 10018 - 10035
(2007/10/03)
-
- Inhibitors of α4β1 mediated cell adhesion
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The present invention relates to compound of formula (I), that are potent inhibitors of α4β1mediated adhesion to either VCAM or CS-1 and which could be useful for the treatment of inflammatory diseases. Specifically, the molecules of the present invention can be used for treating or preventing α4β1adhesion mediated conditions in a mammal such as a human. This method may comprise administering to a mammal or a human patient an effective amount of the compound or composition as explained in the present specification.
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Page/Page column 26
(2010/02/05)
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- Amino acid derivatives and drugs containing the same as the active ingredient
-
The present invention relates to the compounds of the formula (I) and salts thereof (all the symbols are the same meanings as described in the specification). The compounds of the formula (I) possess inhibitory activity of N-type calcium channel, so they are useful as drug for prevention and/or treatment of cerebral infarct, transient ischemic attack, encephalomyelopathy after cardiac operation, spinal angiopathy, hypertension with stress, neurosis, epilepsy, asthma and pollakiuria etc. or agent for the treatment of pain.
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- Azafulvenium methides: New extended dipolar systems
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The transient 1-azafulvenium methides 24, 26 and 28 generated by thermal extrusion of sulfur dioxide from pyrrolo[1,2-c][1,3]thiazole 2,2-dioxide 20 (R = Me), 22 and 23 undergo sigmatropic [1,8]H shifts and the 1-acyl derivatives 30 electrocyclise to give novel pyrrolo[1,2-c][1,3]oxazines 32. The analogous 1,2-diazafulvenium methide 36 has been intercepted in [8π + 2π] cycloadditions with electron-rich silylated acetylenes to give adducts 37-40. This behaviour is partially explained by Frontier MO theory.
- Sutcliffe, Oliver B.,Storr, Richard C.,Gilchrist, Thomas L.,Rafferty, Paul
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p. 1795 - 1806
(2007/10/03)
-
- Radiochemical synthesis and preliminary evaluation of anti-bladder cancer monoclonal antibody BDI-1 labeled with rhenium-188
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The anti-human bladder cancer monoclonal antibody BDI-1 was radio-labeled with rhenium-188 by direct labeling methods using SnCl2 as reductant and MDP as stannous stabilizer or by indirect method using NHS-ECM ester as bifunctional chelator. Radiochemical yields of 30 ± 7.23% and 87.4 ± 5.67% and radiochemical purity of more than 95% were achieved. The inmmunoreactive fraction was 58.7%. The results showed that radionuclide 188Re might be employed using the same labeling methodology with 99mTc labeling of BDI-1 for radiommunoimaging (RII) and radioimmunotherapy (RIT) and that may be useful in radioimmunodetection and RIT of human bladder carcinoma in vivo. Copyright
- Wang, Rongfu,Zhang, Chungli,Yu, Lizhang,Guo, Yifeng,Bai, Ying
-
p. 437 - 444
(2007/10/03)
-
- Azafulvenium methides: New extended dipolar systems
-
The transient 8π 1,7-dipolar azafulvenium methides 5 and 8 undergo sigmatropic [1,8] H shifts and the acyl derivatives 12 electrocyclise to give novel pyrrolooxazines 13; the related diazafulvenium methide 15 can be intercepted in 8π + 2π cycloadditions with silylated acetylenes.
- Sutcliffe, Oliver B.,Storr, Richard C.,Gilchrist, Thomas L.,Rafferty, Paul,Crew, Andrew P. A.
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p. 675 - 676
(2007/10/03)
-
- Quantitative solid-state reactions of amines with carbonyl compounds and isothiocyanates
-
A series of solid-state reactions is reported of gaseous or solid amines with aldehydes to give imines, with solid anhydrides to give diamides (therefrom imides) or amidic carboxylic salts or imides, with solid imides to give diamides, with solid lactones or carbonates to give functionalized carbamic esters, with polycarbonates to give degradative aminolysis, and with solid isothiocyanates to give thioureas. Diamides give imides by solid-state thermolysis or acid catalysis. Various double, two-step, 3-cascade, and sequential reactions are reported in the solid state without melting. The yields are quantitative in 53 reported reaction examples and no workup (except for washings in four cases) is required in the 100% yield reactions. Three initially solid-state reactions but with liquid product were not quantitative. An upscaling to the kg scale shows promise of the technique for large scale applications. Supermicroscopic analyses with AFM elucidate the solid-state mechanism by virtue of far-reaching anisotropic molecular movements in three-step processes. Gas-solid aminolyses of polycarbonates are also studied with AFM. The implications to sustainable chemistry are discussed. (C) 2000 Elsevier Science Ltd.
- Kaupp, Gerd,Schmeyers, Jens,Boy, Juergen
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p. 6899 - 6911
(2007/10/03)
-
- Synthesis and stereochemical studies of 2-substituted thiazolidine-4-carboxamide derivatives
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A series of new 2-substituted thiazolidine-4-carboxamide derivatives which have potentially useful immunological properties, have been synthesized in a stereoselective manner by coupling 2-subsituted thiazolidine-4-carboxylic acids with amines or amino esters. The structure of these compounds was established by combination of NMR methods and by X-ray analysis.
- Refouvelet,Pellegrini,Robert,Crini,Blacque,Kubicki
-
p. 1425 - 1430
(2007/10/03)
-
- An improved stereocontrolled synthesis of pyochelin, siderophore of Pseudomonas aeruginosa and Burkholderia cepacia
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A considerably improved stereocontrolled synthesis of pyochelin, a hydroxyphenylthiazolinylthiazolidine type of siderophore common to most strains of Pseudomonas aeruginosa and Burkholderia cepacia is described. 2'- (2-Hydroxyphenyl)-2'-thiazoline-4'-carboxaldehyde, a key molecule involved in this synthesis has been prepared by reduction of 2'-(2-hydroxyphenyl)-2'- thiazoline-4'-(N-methoxy,N-methyl) carboxamide with lithium aluminium hydride. The aldehyde was further coupled with (R)-N-methylcysteine to yield pyochelin. Under the conditions reported, epimerization at the C-4' center was considerably diminished.
- Zamri, Adel,Abdallah, Mohamed A.
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p. 249 - 256
(2007/10/03)
-
- Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine
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We designed and synthesized a new class of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy- 4-phenylbutyric acid], with a hydroxymethylcarbonyl (HMC) isostere as the active moiety. A systematic evaluation of structure - activity relationships for HIV protease inhibition, anti-HIV activities, and pharmacokinetic profiles has led to the delineation of a set of structural characteristics that appear to afford an orally available HIV protease inhibitor. Optimum structures, exemplified by 21f (JE-2147), incorporated 3-hydroxy-2- methylbenzoyl groups as the P2 ligand, (R)-5,5-dimethyl-1,3-thiazolidine-4- carbonyl (Dmt) residue at the P1' site, and 2-methylbenzylcarboxamide group as the P2' ligand. The present study demonstrated that JE-2147 has potent antiviral activities in vitro and exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals.
- Mimoto, Tsutomu,Kato, Ryohei,Takaku, Haruo,Nojima, Satoshi,Terashima, Keisuke,Misawa, Satoru,Fukazawa, Tominaga,Ueno, Takamasa,Sato, Hideharu,Shintani, Makoto,Kiso, Yoshiaki,Hayashi, Hideya
-
p. 1789 - 1802
(2007/10/03)
-
- New dipeptides containing thiazolidine-4-carboxylic acid derivatives: Synthesis and characterization using NMR techniques and X-ray data
-
New dipeptides, structural analogues of known immunomodulating agents, were prepared by stereospecific condensation between 2-substituted thiazolidine-4-carboxylate esters with N-substituted L-proline or L- thiaproline. The structure of these compounds has been elucidated by combination of NMR methods and X-ray analysis. In addition, NMR measurements on dipeptides indicated the presence of S-cis and S-trans conformers around the amide bonds.
- Pellegrini, Nadia,Refouvelet, Bernard,Crini, Gregorio,Blacque, Olivier,Kubicki, Marek M.,Robert, Jean-Francois
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p. 950 - 955
(2007/10/03)
-
- The use of Curtius rearrangement in the synthesis of 4- aminothiazolidines
-
The amine group of the L-cysteine was protected as (4R)-1,3- thiazolidines-4-carboxylic acids 2a-b and was used for the synthesis of functionalized 1,3-diamines by the way of Curtius reaction. An optimization of this methodology was made using the acylation in situ of the amine group of the thiazolidines and the activation of the carboxylic acid, after Curtius rearrangement yielded the ureas 7a,b and 8a and amine derivatives 6a,b. The Curtius reaction occurred without racemization, preserving the chemical and pharmacological importance of these products.
- Braibante, Mara E.F.,Braibante, Hugo S.,Costenaro, Edson R.
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p. 943 - 946
(2007/10/03)
-
- 14-substituted marcfortines and derivatives useful as antiparasitic agents
-
There are disclosed 14α-hydroxymarcfortine derivatives of the natural products marcfortine A, B, C, and D useful in the treatment and prevention of helminth and arthropod infections of animals and plants. The synthetic derivatives are of Formula (I). STR1
- -
-
-
- Marcfortine/paraherquamide derivatives useful as antiparasitic agents
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There are disclosed 18-thiomarcfortine derivatives of the natural products marcfortine A, B and C, C-18 thioparaherquamide and derivatives thereof, novel N-1 marcfortines A, B, and C and derivatives thereof, novel N-1 paraherquamide and derivatives thereof usefull in the treatment and prevention of helninth and arthropod infections of animals and plants. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Examiner Robert T. Bond whose telephone number is (703)308-4711. The examiner can normally be reached on Monday through Friday from 8:00 AM to 4:30 PM.
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-
-
- Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones
-
This invention relates to compounds of Formula I STR1 which are useful in association with a pharmaceutical carrier as antiatherosclerotic agents. In addition, various compounds of Formula I are useful inhibitors of cell proliferation.
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-
-
- Protected Derivatives of (R)-Cysteine and (R)-Cysteinol
-
The synthesis of N, O, S protected forms of (R)-cysteine and (R)-cysteinol as bicyclic derivatives is described.The reactivity and the preparation of substituted derivatives of these systems is also discussed.
- Gonzalez, Asensio,Lavilla, Rodolfo,Piniella, Juan F.,Alvarez-Larena, Angel
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p. 3015 - 3024
(2007/10/02)
-
- Preparations of Optically Active Homocysteine and Homocystine by Asymmetric Transformation of (RS)-1,3-Thiazane-4-carboxylic Acid
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DL-Homocysteine from (RS)-homocysteine thiolactone hydrochloride was subjected to reaction with formaldehyde in acetic acid to give (RS)-1,3-thiazane-4-carboxylic acid monohydrate .An asymmetric transformation of (RS)-THA*H2O was achieved via salt formation with optically active tartaric acid in the presence of salicylaldehyde in acetic acid.The (R)- and (S)-THA obtained, respectively, from the salt of (R)-THA with (2R,3R)-tartaric acid and its enantiomeric salt were treated with hydroxylamine hydrochloride to give D- and L-Hcy of 100percent optical purity, respectively, in 50percent yield from (RS)-HTL*HCl.Oxidation of D- and L-Hcy with hydrogen peroxide gave D- and L-homocystine, respectively, in 47percent yield.
- Miyazaki, Hideya,Ohta, Atsushi,Kawakatsu, Nobuyuki,Waki, Yukitaka,Gogun, Yasuhiro,et al.
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p. 536 - 540
(2007/10/02)
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- Antiatherosclerotic and antithrombotic 2-amino-6-phenyl-4H-pyran-4-ones
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This invention relates to compounds of Formula I STR1 which are useful as antiatherosclerotic agents and inhibitors of cell proliferation for the treatment of proliferative diseases. In addition, various compounds of Formula I are useful inhibitors of platelet aggregation.
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- Optical Resolution by Replacing Crystallization of (RS)-4-Thiazolidinecarboxylic Acid with L-Amino Acids as Cosolute
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The optical resolution by replacing crystallization of (RS)-4-thiazolidinecarboxylic acid was carried out with coexisting eight L-amino acids and the effect of the latter was examined.L-Isoleucine and L-cysteine as the cosolute led to preferential crystallization of (R)-THC from an aqueous solution of (RS)-THC, whereas the other L-amino acids gave (S)-THC.L-Cys, L-threonine, L-4-hydroxyproline , and L-serine as the cosolute seemed to give better selectivity for crystallization of one enantiomer than L-Ile, L-valine, L-proline, and L-alanine.The optical resolution with L-Hyp was successfully achieved and suggested a possibility of successive optical resolution to give both (R)- and (S)-THC.
- Shiraiwa, Tadashi,Yamauchi, Masahiro,Tatsumi, Takeshi,Kurokawa, Hidemoto
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p. 267 - 273
(2007/10/02)
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- Asymmetric Transformation of (RS)-Cysteine via Formation of (RS)-4-Thiazolidinecarboxylic Acids
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Either (R)- or (S)-cysteine ((R)- or (S)-Cys) was efficiently obtained from (RS)-Cys by the asymmetric transformation via formation of (RS)-thiazolidinecarboxylic acid ((RS)-THC) or (RS)-2,2-dimethyl-4-thiazolidinecarboxylic acid ((RS)-DMZ) and by using (2R,3R)- or (2S,3S)-tartaric acid ((R)- or (S)-TA), as a resolving agent, in acetic acid.The asymmetric transformation was carried out by combination of crystallization of less soluble salt of (S)-THC or -DMT with (R)-TA (or salt of (R)-THC or -DMT with (S)-TA) and epimerization of soluble diastereomeric salt.The (R)- and (S)-THCs from the less soluble salts gave approximately optically pure (R)- and (S)-Cys's, respectively, in 64percent yield.The asymmetric transformation via formation of (RS)-DMT was more succeefully achieved by adding 0.1 molar equivalent of salicylaldehyde; that is, hydrolysis of the obtained less soluble salt gave optically pure (R)- and (S)-Cys's, respectively, in 80percent yield based on the (RS)-Cys used as the starting material.
- Shiraiwa, Tadashi,Kataoka, Kazuo,Sakata, Shinji,Kurokawa, Hidemoto
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p. 109 - 113
(2007/10/02)
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- A Dipolar Cycloaddition Approach to Pyrroloindoles Using N--Substituted Indoles
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The 1,3-dipolar cyloaddition of a number of N--substituted indoles with several dipolarophiles has been investigated.The reaction requires the use of an equivalent amount of silver fluoride and provides a direct and efficient synthesis of the pyrroloindole ring system.The structures of the cycloadducts were established by high-field NMR spectroscopy as well as by several X-ray crystal structures.The cycloaddition reactions show all the characteristics of a concerted reaction, including complete stereospecificity and regioselectivity.The results are consistent with a mechanism that involves the intermediacy of an azomethine ylide.Formation of the dipole is rationalized by assuming that silver ion behaves as a very specific Lewis acid that attacks the indole ring to give a silver bonded carbonium ion.This is followed by a rapid desilylation reaction to give the azomethine ylide.After the cycloaddition step, the resulting silver-bonded intermediate undergoes consecutive loss of silver and a hydrogen to give the observed product.Attempts to extend the cycloaddition methodology to N--substituted enamines and pyrroles are also described.
- Padwa, Albert,Fryxell, Glen E.,Gasdaska, John R.,Venkatramanan, M. K.,Wong, George S. K.
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p. 644 - 653
(2007/10/02)
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- Asymmetric Transformation of DL-4-Thiazolidinecarboxylic Acid
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A mixture of DL-4-thiazolidinecarboxylic acid (DL-THC), (+)- or (-)-tartaric acid ((+)- or (-)-TA), and salicylaldehyde in acetic acid was stirred at 80 deg C to give a salt composed of equimolar amounts of L-THC and (-)-TA or that of D-THC and (+)-TA.D- and L-THC with optical purity of 97-99percent were obtained from these salts in 68-78percent yield.
- Shiraiwa, Tadashi,Kataoka, Kazuo,Kurokawa, Hidemoto
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p. 2041 - 2042
(2007/10/02)
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- Optical Resolution by Preferential Crystallization of DL-Thiazolidine-4-carboxylic Acid
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Infrared spectrum, solubility, and ternary solubility diagram indicated that DL-thiazolidine-4-carboxylic acid (DL-THC) is a conglomerate at room temperature.The free energy of critical nucleation in supersaturated solutions for the crystallization of D- and L-THC was examined to resolve DL-THC efficiently by preferential crystallization.Successive preferential crystallization of DL-THC was experimented at 20 deg C for an aqueous racemic solution with a supersaturation of 150percent, and D- and L-THC with optical purity 96-100percent were obtained in the range of resolution of 58-76percent.The optical resolution was more succesfully done in 1 mol dm-3 aqueous glycine to give D- and L-THC with optical purity of 93-99percent in the degree of resolution of 77-87percent.Recrystallization of D- and L-THC obtained with a succeeding treatment with hydroxylamine hydrochloride gave D- and L-cysteine with 100percent optical purity.
- Shiraiwa, Tadashi,Sado, Yujin,Komure, Masamitsu,Kurokawa, Hidemoto
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p. 3277 - 3284
(2007/10/02)
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- Amino-acid zwitterion equilibria: vibrational and nuclear magnetic resonance studies of methyl-substituted thiazolidine-4-carboxylic acids
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Infrared and Raman spectra (4000-100 cm-1) of solid samples of six different methyl substituted thiazolidine products of D-penicillamine and L-cysteine hydrochloride have been observed and assigned, Infrared spectra in D2O solutions have been obtained for comparison in order to study the amino-acid zwitterion equilibria.Proton and 13C nmr spectra for the compounds have also been measured.
- Howard-Lock, H. E.,Lock, C. J. L.,Martins, M. L.,Smalley, P. S.,Bell, R. A.
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p. 1215 - 1219
(2007/10/02)
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- Thiolic derivatives of erythromycin having therapeutic activity, and pharmaceutical compositions containing them
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The thiolic salts of erythromycin and of the propionic ester of erythromycin with thenoyl alpha-mercaptopropionylglycine find therapeutical use in the cases in which erythromycin or its propionic ester are used and are generally endowed with very low toxicity and high hematic levels.
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- Treatment of atherosclerosis with khellin-related furochromones
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The present specification relates to the antiatherosclerotic use of khellin and related furochromones, and further provides novel antiatherogenic furochromones.
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- Antiatherosclerotic furochromones
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The present specification relates to the antiatherosclerotic use of khellin and related furochromones, and further provides novel antiatherogenic furochromones.
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