cas 4248-19-5, tert-Butyl carbamate | Articles data

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Skeletally Tunable Seven-Membered-Ring Fused Pyrroles
We describe a copper-mediated method that enables the synthesis of seven-membered-ring fused pyrroles (7-mrFPs). The protocol proceeds via an in situ spiro-intermediate ring expansion and tolerates a library of 7-mrFP derivatives with a broad range of functional groups in a simple step with tangible parameters and substrate adaptations. These rare 7-mrFPs are now accessible on a millimolar scale, and selected examples exhibit high antioxidant activity.
Andreou, Dimitrios,Essien, Nsikak B.,Pubill-Ulldemolins, Cristina,Terzidis, Michael A.,Papadopoulos, Athanasios N.,Kostakis, George E.,Lykakis, Ioannis N.
supporting information
p. 6685 - 6690
(2021/09/11)

Controlled Relay Process to Access N-Centered Radicals for Catalyst-free Amidation of Aldehydes under Visible Light
Nitrogen-centered radicals have attracted increasing attention as a versatile reactive intermediate for diverse C–N bond constructions. Despite the significant advances achieved in this realm, the controllable formation of such species under catalyst-free conditions remains highly challenging. Here, we report a new relay process involving the slow in situ generation of a photoactive N-chloro species via C–N bond formation, which subsequently enables mild and selective access to N-centered radicals under visible light conditions. The utility of this approach is demonstrated by the conversion of aldehydes to amides, employing N-chloro-N-sodio carbamates as a practical amidating source. This synthetic operation obviates the need for catalysts, external oxidants, and coupling reagents that are typically required in related processes, consequently allowing high functional group tolerance and excellent applicability for late-stage functionalization. Amides are an important class of structural motifs prevalently found in bioactive compounds and synthetic materials of great significance. Amidation of aldehydes has been established as an atom-efficient strategy for amide synthesis; however, current methods lack in applicability mainly due to the requirement of troublesome reagents. In this article, we describe an unconventional relay process to convert aldehydes to amides under catalyst-, oxidant-, and coupling-reagent-free conditions, which is enabled by the development of a new mechanistic platform that gives efficient and controllable access to N-centered radicals under visible light. A wide range of (hetero)aromatic and aliphatic aldehydes can be employed, including those derived from biologically relevant complex molecules. We anticipate that the accomplished methodological advances, combined with the unique mechanistic features, will lead to the widespread application of the present strategy in broad research fields. A catalyst-free approach for controlled access to N-centered radicals is described, which enables the conversion of aldehydes to amides via an unconventional relay process harnessing visible light. The key tactic relies on the use of photostable N-chloro-N-sodio-carbamate amidating reagent that leads to slow incorporations of a photoactive radical source via C–N formation and other involved intermediates thereafter. This methodology displays excellent applicability and sustainable chemistry credentials and, thus, holds a promise for finding broad applications.
Chang, Sukbok,Jeon, Hyun Ji,Jung, Hoimin,Kim, Dongwook,Lee, Wongyu,Seo, Sangwon
supporting information
p. 495 - 508
(2021/01/28)

Stepwise dual targeting and dual responsive polymer micelles for mitochondrion therapy
Methods to selectively destroy mitochondria of tumor cells and induce cell apoptosis with nanomedicine constitute challenges in cancer therapy. In the present study, we develop cell membrane/mitochondria dual targeting and pH/redox dual responsive nanoparticles for mitochondrion therapy. The nanoparticles are fabricated by the self-assembly of triphenylphosphonium (TPP) grafted poly(ethylene glycol)(PEG)-poly(d,L-lactide)(PLA) copolymers (TPP-PEG-ss-PLA) using disulfide bonds as the intermediate linkers. To shield the surface positive charge of the nanoparticles from TPP composition, chondroitin sulfate (CS) is employed to coat the nanoparticles, and this prolongs blood circulation while endowing an active targeting ability to the cell membrane. In acidic lyso-somes/endosomes, the negatively charged CS layer falls away to expose the TPP component. Subsequently, in the cyto-plasm, the nanoparticles can anchor to the mitochondrial outer membrane by TPP-mediated targeting, thereby inducing a decrease in the membrane potential and opening of the permeability transition pore. Thus, the overproduction of ROS in the mitochondria promotes cell apoptosis. The released DOX directly diffuse into the mitochondria, thereby resulting in mito-chondrial DNA damage. Therefore, the nanoparticles exhibit significant potential in terms of a new avenue for mitochondrion therapy in cancer treatment.
Wang, Yi,Wei, Guoqing,Yang, Guang,Zhang, Xiaobin,Zhao, Jingya,Zhou, Shaobing
p. 157 - 169
(2020/03/26)

An efficient one-pot synthesis of industrially valuable primary organic carbamates and: N -substituted ureas by a reusable Merrifield anchored iron(ii)-anthra catalyst [FeII(Anthra-Merf)] using urea as a sustainable carbonylation source
An efficient synthesis of primary carbamates and N-substituted ureas is explored with a newly developed heterogeneous polymer supported iron catalyst in the presence of a sustainable carbonylation source. The Merrifield anchored iron(ii)-anthra catalyst [FeII(Anthra-Merf)] was synthesized by functionalization of Merrifield polymer followed by grafting of iron metal. The catalyst [FeII(Anthra-Merf)] was characterized by several techniques, like SEM, EDAX, TGA, PXRD, XPS, FTIR, CHN, AAS and UV-Vis analysis. The designed polymer embedded [FeII(Anthra-Merf)] complex is a remarkably successful catalyst for the synthesis of primary organic carbamates and N-substituted ureas by using safe carbonylation agent urea with different derivatives of alcohols and amines, respectively. The reported catalyst is a potential candidate towards contributing a satisfactory yield of isolated products under suitable reaction conditions. The catalyst is recyclable and almost non-leaching in nature after six runs with an insignificant drop in catalytic activity. Thus we found an economical and viable catalyst [FeII(Anthra-Merf)] for primary carbamates and N-substituted urea synthesis under moderate reaction conditions.
Basu, Priyanka,Dey, Tusar Kanto,Ghosh, Aniruddha,Biswas, Surajit,Khan, Aslam,Islam, Sk. Manirul
p. 2630 - 2643
(2020/02/20)

An Fe3O4@SiO2/Schiff base/Cu(ii) complex as an efficient recyclable magnetic nanocatalyst for selective mono: N-arylation of primary O-alkyl thiocarbamates and primary O-alkyl carbamates with aryl halides and arylboronic acids
An efficient, convenient and novel method for the selective mono N-arylation of primary O-alkyl thiocarbamates and primary O-alkyl carbamates with aryl halides and arylboronic acids in the presence of a recyclable magnetic Cu(ii) nanocatalyst is described. A variety of mono N-arylated O-alkyl thiocarbamates and O-alkyl carbamates were prepared in good to excellent yields with a broad range of aryl coupling partners. The magnetic nanocatalyst can be easily recovered with an external magnetic field and reused at least five times without noticeable leaching or loss of its catalytic activity. This cost-effective and eco-friendly methodology has some other advantages, such as easy preparation of the catalyst, simple workup procedure, and easy purification, which makes this protocol interesting for the users in various fields of pharmacology and biotechnology systems.
Sardarian, Ali Reza,Dindarloo Inaloo, Iman,Zangiabadi, Milad
p. 8557 - 8565
(2019/06/14)

Superparamagnetic Fe3O4 Nanoparticles in a Deep Eutectic Solvent: An Efficient and Recyclable Catalytic System for the Synthesis of Primary Carbamates and Monosubstituted Ureas
Superparamagnetic Fe3O4 nanoparticles were used to synthesize various primary carbamates as well as monosubstituted and N,N-disubstituted ureas. This efficient phosgene-free process used urea as an eco-friendly carbonyl source in the presence of a biocompatible deep eutectic solvent (DES) to provide an inexpensive and attractive route that afforded the products in moderate to excellent yields. The employed DES serves both a catalytic role and as the green reaction medium. The magnetic nanocatalyst and DES can been reused several times without a significant loss of activity.
Inaloo, Iman Dindarloo,Majnooni, Sahar,Esmaeilpour, Mohsen
p. 3481 - 3488
(2018/07/29)

Design and Synthesis of Iminosydnones for Fast Click and Release Reactions with Cycloalkynes
Emerging applications in the field of chemical biology are currently limited by the lack of bioorthogonal reactions allowing both removal and linkage of chemical entities on complex biomolecules. We recently discovered a novel reaction between iminosydnones and strained alkynes leading to two products resulting from ligation and fragmentation of iminosydnones under physiological conditions. We now report the synthesis of a panel of substituted iminosydnones and the structure reactivity relationship between these compounds and strained alkyne partners. This study identified the most relevant substituents, which allow to increase the rate of the transformation and to develop a bifunctional cleavable linker with improved kinetics.
Riomet, Margaux,Decuypere, Elodie,Porte, Karine,Bernard, Sabrina,Plougastel, Lucie,Kolodych, Sergii,Audisio, Davide,Taran, Frédéric
p. 8535 - 8541
(2018/05/30)

Selective Synthesis of Secondary Arylcarbamates via Efficient and Cost Effective Copper-Catalyzed Mono Arylation of Primary Carbamates with Aryl Halides and Arylboronic Acids
Abstract: An efficient, selective and cost-effective procedure has been developed for mono N-arylation of primary alkyl and benzyl carbamates with aryl iodides and bromides by incorporating CuI as an inexpensive and commercially available catalyst. Despite previous reports on C–N coupling reactions, this process does not need expensive ligands and takes advantage of readily available and inexpensive ethylenediamine (EDA) as the ligand. Reaction times were relatively short and related N-arylated carbamates were obtained in excellent yields. Interestingly, replacing CuI with Cu(OAc)2 allowed us to use arylboronic acids as coupling partner for this reaction. All products are well characterized by 1H- and 13C-NMR, MS, melting point, IR and CHNS techniques.
Sardarian, Ali Reza,DindarlooInaloo, Iman,Zangiabadi, Milad
p. 642 - 652
(2018/01/11)

Bioorthogonal Click and Release Reaction of Iminosydnones with Cycloalkynes
We report the discovery of a new bioorthogonal click-and-release reaction involving iminosydnones and strained alkynes. This transformation leads to two products resulting from the ligation and fragmentation of iminosydnones under physiological conditions. Optimized iminosydnones were successfully used to design innovative cleavable linkers for protein modification, thus opening up new areas in the fields of drug release and target-fishing applications. This click-and-release technology offers the possibility of exchanging tags on proteins for functionalized cyclooctynes under mild and bioorthogonal conditions.
Bernard, Sabrina,Audisio, Davide,Riomet, Margaux,Bregant, Sarah,Sallustrau, Antoine,Plougastel, Lucie,Decuypere, Elodie,Gabillet, Sandra,Kumar, Ramar Arun,Elyian, Jijy,Trinh, Minh Nguyet,Koniev, Oleksandr,Wagner, Alain,Kolodych, Sergii,Taran, Frédéric
supporting information
p. 15612 - 15616
(2017/12/02)

Fe3O4@SiO2/Schiff base/Pd complex as an efficient heterogeneous and recyclable nanocatalyst for chemoselective: N -arylation of O -alkyl primary carbamates
An efficient, heterogeneous and cost effective method has been developed using an Fe3O4@SiO2/Schiff base/Pd complex as a magnetic and easily recyclable nanocatalyst for rapid and effective N-arylation of carbamates in good to excellent yield. The catalyst can be easily recovered and reused over six runs without significant decrease in the activity. Further highlights of this protocol are operational simplicity, versatility and relatively short reaction times.
Sardarian,Zangiabadi,Inaloo, I. Dindarloo
p. 92057 - 92064
(2016/10/11)

4-Dodecylbenzenesulfonic acid (DBSA) promoted solvent-free diversity-oriented synthesis of primary carbamates, S-thiocarbamates and ureas
A simple and highly efficient solvent-free method for the conversion of alcohols, phenols, thiols and amines to primary carbamates, S-thiocarbamates and ureas in the presence of 4-dodecylbenzenesulfonic acid (DBSA) as a cheap and green Bronsted acid reagent has been described. All products were obtained in good to excellent yields and characterized using FT-IR, 1H- and 13C-NMR, MS and CHNS techniques.
Sardarian, Ali Reza,Inaloo, Iman Dindarloo
p. 76626 - 76641
(2015/09/22)

Chemoenzymatic Synthesis of Optically Pure l- and d-Biarylalanines through Biocatalytic Asymmetric Amination and Palladium-Catalyzed Arylation
A chemoenzymatic approach was developed and optimized for the synthesis of a range of N-protected nonnatural l- and d-biarylalanine derivatives. Starting from 4-bromocinnamic acid and 4-bromophenylpyruvic acid using a phenylalanine ammonia lyase (PAL) and an evolved d-amino acid dehydrogenase (DAADH), respectively, both enantiomers of 4-bromophenylalanine were obtained and subsequently coupled with a panel of arylboronic acids to give the target compounds in high yield and optical purity under mild aqueous conditions.
Ahmed, Syed T.,Parmeggiani, Fabio,Weise, Nicholas J.,Flitsch, Sabine L.,Turner, Nicholas J.
p. 5410 - 5413
(2015/09/15)

METHODS OF INCORPORATING AN AMINO ACID COMPRISING A BCN GROUP INTO A POLYPEPTIDE USING AN ORTHOGONAL CODON ENCODING IT AND AN ORTHORGONAL PYLRS SYNTHASE
The invention relates to a polypeptide comprising an amino acid having a bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) group, particularly when said BCN group is present as: a residue of a lysine amino acid. The invention also relates to a method of producing a polypeptide comprising a BCN group, said method comprising genetically incorporating an amino acid comprising a BCN group into a polypeptide. The invention also relates to an amino acid comprising bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN), particularly and amino acid which is bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) lysine. In addition the invention relates to a PylRS tRNA synthetase comprising the mutations Y271M, L274G and C313A.
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(2015/06/03)

Ammonolysis of anilides promoted by ethylene glycol and phosphoric acid
Ethylene glycol (EG) and phosphoric acid have been found to promote the ammonolysis of a variety of diverse anilides as well as N-aryl carbamate, phthalimide, and urea substrates in the absence of transition metals or other Lewis acid promoters.
Stephenson, Nickeisha A.,Gellman, Samuel H.,Stahl, Shannon S.
p. 46840 - 46843
(2014/12/10)

AMINOTHIAZOLES AND THEIR USES
The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases.
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(2014/10/29)

SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE
The present invention provides novel substituted cyclic compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 0181

(2013/09/26)

Bromenium-catalysed tandem ring opening/cyclisation of vinylcyclopropanes and vinylcyclobutanes: A metal-free [3+2+1]/[4+2+1] cascade for the synthesis of chiral amidines and computational investigation
We present a detailed study of a [3+2+1] cascade cyclisation of vinylcyclopropanes (VCP) catalysed by a bromenium species (Br δ+-Xδ-) generated in situ, which results in the synthesis of chiral bicyclic amidines in a tandem one-pot operation. The formation of amidines involves the ring-opening of VCPs with Br-X, followed by a Ritter-type reaction with chloramine-T and a tandem cyclisation. The reaction has been further extended to vinylcyclobutane systems and involves a [4+2+1] cascade cyclisation with the same reagents. The versatility of the methodology has been demonstrated by careful choice of VCPs and VCBs to yield bicyclo[4.3.0]-, -[4.3.1]- and -[4.4.0]amidines in enantiomerically pure form. On the basis of the experimental observations and DFT calculations, a reasonable mechanism has been put forth to account for the formation of the products and the observed stereoselectivity. We propose the existence of a π-stabilised homoallylic carbocation at the cyclopropane carbon as the reason for high stereoselectivity. DFT studies at B3LYP/6-311+G** and M06-2X/6-31+G* levels of theory in gas-phase calculations suggest the ring-opening of VCP is initiated at the π-complex stage (between the double bond and Br-X). This can be clearly perceived from the solution-phase (acetonitrile) calculations using the polarisable continuum model (PCM) solvation model, from which the extent of the ring opening of VCP was found to be noticeably high. Studies also show that the formation of zero-bridge bicyclic amidines is favoured over other bridged bicyclic amidines. The energetics of competing reaction pathways is compared to explain the product selectivity. Copyright
Ganesh, Venkataraman,Sureshkumar, Devarajulu,Chanda, Debasree,Chandrasekaran, Srinivasan
supporting information
p. 12498 - 12511,14
(2020/08/24)

Diastereo- and enantioselective Pd(II)-catalyzed additions of 2-alkylazaarenes to N -boc imines and nitroalkenes
A chiral Pd(II)-bis(oxazoline) complex was found to be highly effective in promoting the first direct diastereo- and enantioselective addition of alkylazaarenes to N-Boc aldimines and nitroalkenes under mild conditions. Deprotection of Boc-protected products proceeded readily to provide amines in high yields.
Best, Daniel,Kujawa, Szymon,Lam, Hon Wai
supporting information
p. 18193 - 18196
(2013/01/15)

CHEMICAL MODIFICATIONS OF MONOMERS AND OLIGONUCLEOTIDES WITH CYCLOADDITION
The invention features compounds of formula I or II: In one embodiment, the invention relates compounds and processes for conjugating ligand to oligonucleotide. The invention further relates to methods for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, cancers, allergies, autoimmune diseases, immunodeficiencies and immunosuppression.
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(2012/02/15)

SELECTIVE ANTICONVULSANT AGENTS AND THEIR USES
In preferred embodiments, the present invention provides methods of treatment and pharmaceutical compositions for the suppression, alleviation and prevention of seizures. The preferred embodiments of the present invention further relate to methods of treatment and pharmaceutical compositions using benzodiazepine derivatives that provide suppression, alleviation and prevention of seizures with reduced sedative and ataxic side effects.
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(2010/11/03)

PREPARATION OF SITAGLIPTIN INTERMEDIATE
Intermediate compounds in the synthesis of Sitagliptin, 3-amino-4-(2,4,5- trifluorophenyl)but-2-enoic acid alkyl ester, and amino protected-3-amino-4-(2,4,5- trifluorophenyl)but-2-enoic acid alkyl ester, and the stereoselective reduction of these compound to give Synthon I, or the amino-protected Synthon I, are provided.
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(2009/06/27)

Silica supported perchloric acid (HClO4-SiO2): an efficient reagent for the preparation of primary carbamates under solvent-free conditions
The synthesis of primary carbamates from structurally diverse compounds containing a hydroxyl group has been performed in high yields and purity, and without any epimerization under solvent-free conditions using HClO4-SiO2 as a mild, convenient, and effective reagent. The procedure is operationally simple, efficient, and environmentally benign.
Modarresi-Alam, Ali Reza,Khamooshi, Ferydoon,Nasrollahzadeh, Mahmoud,Amirazizi, Homeyra Alsadat
p. 8723 - 8726
(2008/02/11)

N-heterocyclic inhibitors of TNF-α expression
N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula I: Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-α expression utilizing compounds of the present invention are also disclosed.
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(2008/06/13)

Synthesis and application of procainamide analogs for use in an immunoassay
The present invention relates to immobilized procainamide analogs, as well as to a method of making immobilized procainamide analogs. These immobilized analogs are prepared by activating the carboxyl group on a substituted p-benzoic acid derivative toward nucleophilic attack; reacting the activated benzoic acid derivative with a polyamine to produce the benzoic acid derivative of Formula 3: and binding the benzoic acid derivative of Formula 3 to a latex polymer having functional groups that react with aliphatic amino groups. A method of conducting an immunoassay using the immobilized procainamide analog Formula 3 is described, comprising the steps of preparing a solution comprising said immobilized procainamide analog; adding a sample suspected of containing procainamide to said solution; adding an anti-procainamide antibody to said solution and observing the rate of increase in solution turbidity following antibody addition.
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(2008/06/13)

Synthesis of epothilones, intermediates thereto and analogues thereof
The present invention provides convergent processes for preparing epothilones, desoxyepothilones, and analogues thereof. The present invention further provides novel compositions and methods for the treatment of cancer and additionally provides methods for the treatment of cancer which has developed a multi-drug phenotype.
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(2008/06/13)

Sulfonyl aryl hydroxamates and their use as matrix metalloprotease inhibitors
This invention is directed to sulfonyl aromatic hydroxamic acid compounds and salts thereof that, inter alia, inhibit matrix metalloprotease (MMP) activity and/or aggrecanase activity. In some particularly preferred embodiments, the compound corresponds in structure to one of the following formulas: wherein W2, the R groups, and —A—R—E—Y are described in more detail in Applicants' specification. This invention also is directed to a process that comprises administering such a compound or pharmaceutically acceptable salt thereof to a host animal having a condition associated with MMP activity.
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(2008/06/13)

HIV protease inhibitors, compositions containing the same, their pharmaceutical uses, material for their synthesis
Compounds of the formula: where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the HIV protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with the HIV virus. Intermediates and synthetic methods for preparing such compounds are also described.
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(2008/06/13)

HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis
The present invention concerns processes for preparing compounds of formula (I-H), or a prodrug, pharmaceutically active metabolite, or pharmaceutically active salt or solvate thereof, which are useful as inhibitors of the HIV protease enzyme.
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(2008/06/13)

Benzylcycloalkyl amines as modulators of chemokine receptor activity
The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of inflammatory diseases such as asthma and other allergic diseases.
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(2011/03/17)

Compounds useful as anti-inflammatory agents
Disclosed are novel aromatic compounds of the formula(I) wherein G, E, W, Ar, X, Y and Z. The compounds are useful for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are pharmaceutical compositions containing and processes of making such compounds.
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(2008/06/13)

Novel carbamate and oxamide compounds
Disclosed are novel aromatic compounds of the formula(I) described herein, wherein G, E, W, Ar, X, Y and Z are disclosed herein. The compounds are useful for treating cytokine mediated diseases or conditions such as chronic inflammatory diseases. Also disclosed are pharmaceutical compositions containing and processes of making such compounds.
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(2008/06/13)

Sulfonyl aryl or heteroaryl hydroxamic acid compounds
A sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.
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(2008/06/13)

SULFONYL ARYL HYDROXAMATES AND THEIR USE AS MATRIX METALLOPROTEASE INHIBITORS
This invention is directed to sulfonyl aromatic hydroxamic acid compounds and salts thereof that, inter alia, inhibit matrix metalloprotease (MMP) activity and/or aggrecanase activity. In some particularly preferred embodiments, the compound corresponds in structure to one of the following formulas: wherein W2, the R groups, and--A--R--E--Y are described in more detail in Applicants' specification. This invention also is directed to a process that comprises administering such a compound or pharmaceutically acceptable salt thereof to a host animal having a condition associated with MMP activity.
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(2008/06/13)

Use of sulfonyl aryl or heteroaryl hydroxamic acids and derivatives thereof as aggrecanase inhibitors
This invention is directed to a process for inhibiting aggrecanase activity. The process comprises administering a therapeutically effective amount of a sulfonyl aromatic or heteroaromatic hydroxamic acid, a derivative thereof, or a pharmaceutically acceptable salt of the hydroxamic acid or derivative to a host animal. The compound generally corresponds in structure to the following formula: wherein W and the R groups are described in more detail in Applicants' specification.
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(2008/06/13)

Synthesis of α,β-substituted amino amides, esters, and acids
α,β-Unsaturated amides and esters are converted to α,β-substituted amino amides, esters, and acids. An α,βunsaturated amide or ester is first converted to an α,β-hydroxysulfonamide or hydroxycarbamate amide or ester using an osmium-catalyzed aminohydroxylation. The α,β-hydroxysulfonamide or hydroxycarbamate amides or esters is then cyclodehydrated to produce a α,β-N-sulfonyl- or the α,β-N-carbamoylaziridine amide or ester. The ring of aziridine intermediate is then nucleophilically opened in a regioselective manner with a variety of nucleophiles to give the γ(α,β-substituted amino- amides or esters. Preferred nucleophiles include sulfur, oxygen, carbon, and nitrogen nucleophiles.
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(2008/06/13)

HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis
Compounds of the formula: where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the HIV protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with the HIV virus. Intermediates and synthetic methods for preparing such compounds are also described.
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(2008/06/13)

N-heterocyclic inhibitors of TNF-alpha expression
N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula I: Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-α expression utilizing compounds of the present invention are also disclosed.
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(2008/06/13)

N- heterocyclic inhibitors of TNF-alpha expression
N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula I: Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-α expression utilizing compounds of the present invention are also disclosed.
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(2008/06/13)

Compounds useful as anti-inflammatory agents
Disclosed are novel aromatic compounds of the formula(I) wherein G, E, W, Ar, X, Y and Z. The compounds are useful for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are pharmaceutical compositions containing and processes of making such compounds.
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(2008/06/13)

Synthesis of epothilones, intermediates thereto and analogues thereof
The present invention provides convergent processes for preparing epothilones, desoxyepothilones, and analogues thereof. The present invention further provides novel compositions and methods for the treatment of cancer and additionally provides methods for the treatment of cancer which has developed a multi-drug phenotype.
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(2008/06/13)

Sulfamato hydroxamic acid metalloprotease inhibitor
A sulfamato hydroxamic acid compound that, inter alia, inhibits matrix metalloprotease (mmp) activity is disclosed as are a process for preparing the same, intermediate compounds useful in those syntheses, and a treatment process that comprises administering a contemplated sulfamato hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.
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(2008/06/13)

Practical synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine
Three synthetic methods for the preparation of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, an important intermediate in the synthesis of the novel quinolone antitumur agent, AG-7352, have been developed. By one route, an efficient and large-scale preparation of the chiral pyrrolidine could be achieved through resolution of (±)-1-Boc-3-benzylamino-4-hydroxypyrrolidine, which is prepared from either 3-pyrroline or 1,4-dichloro-2-butene.
Tsuzuki, Yasunori,Chiba, Katsumi,Mizuno, Kazuhiro,Tomita, Kyoji,Suzuki, Kenji
p. 2989 - 2997
(2007/10/03)

Acetylenic α-amino acid-based sulfonamide hydroxamic acid tace inhibitors
Compounds of the formula: are useful in treating disease conditions mediated by TNF-α, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.
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(2008/06/13)

Anthranilic acid derivatives as multi drug resistance modulators
Anthranilic acids of formula (I): wherein each of R to R9is an organic substituent, n is 0 or 1, m is 0 or an integer of 1 to 6, q is 0 or 1, X is a direct bond, O, S, —S—(CH2)por —O—(CHO2)p— wherein p is from 1 to 6 and Ar is an unsaturated carbocyclic or heterocyclic group, and the pharmaceutically acceptable salts thereof, have activity as inhibitors of P-glycoprotein and may thus be used, inter alia, as modulators of multidrug resistance in the treatment of multidrug resistant cancers, for example to potentiate the cytotoxicity of a cancer drug.
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(2008/06/13)

Inhibitors of protein isoprenyl transferases
Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (d) —C(O)NH—CH(R14)—C(O)NHSO2R16, (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, and —P(W)RR3RR3′; R4is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4—L6—C(W)—N(R5)—L5—, (e) —L4—L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7—L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene (k) a covalent bond, (l) and (m) are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
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(2008/06/13)

Nitro-[2,1-b]imidazopyran compounds and antibacterial uses thereof
Methods, compounds and compositions are provided for inhibiting the growth of pathogenic microbes in vitro and of treatment of pathogenic bacterial infections, such as mycobacterial, Clostridium, Cryptosporidium and Helicobacter infections, in vivo using bicyclic nitroimidazole compounds of the formula (II): STR1 wherein R1 is hydrogen, halogen, loweralkyl, haloloweralkyl, cycloalkyl, heterocycle, substituted heterocycle and heterocyclicalkyl; X is oxygen, sulfur or NR2, where R2 is hydrogen, loweralkyl, aryl, cycloalkyl, heterocycle, substituted heterocycle, heterocyclicalkyl, COR3 or SO2 R4 CONR4 R5, where R3, R4 and R5 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxyalkyl, alkoxyaryl, alloxyalkoxyaryl, alkylheterocycle, and alkoxyheterocycle; n is 1, 2 or 3; Y and Z are independently selected from oxygen, CH2, CO, CR4 R5 or NR4, where R4 and R5 are as defined above; provided that when n is 2 or 3, the compounds of formula II can be additionally substituted as follows: STR2 wherein R6, R7, R8 and R9 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxyalkyl, alkoxyalkylaryl, alkoxyalkylheterocycle, alkylary2alkylaryl, alkylarylaryl, alkylcycloalkyl, alkoxyaryl, alkylheterocycle, and alkoxyheterocycle; and the pharmaceutically acceptable salts thereof.
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(2008/06/13)

Lactam metalloprotease inhibitors
The present application describes novel lactams and derivatives thereof of formula I: or pharmaceutically acceptable salt forms thereof, wherein rings ring B is a 4-8 membered cyclic amide containing from 0-3 additional heteroatoms selected from N, O, and S, which are useful as metalloprotease inhibitors.
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(2008/06/13)

Antibiotic for methicillin resistant bacteria
The present invention is directed to anti-bacterial and anti-tumor agents and the synthesis thereof.
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(2008/06/13)

Therapeutic neurokinin receptor antagonist compounds
Compounds of formula I wherein Q1, Q2, Q3, and Q4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists Substance P and NKA, useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.
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(2008/06/13)

THF-CONTAINING SULFONAMIDE INHIBITORS OF ASPARTYL PROTEASE
The present invention relates to a class of THF-containing sulfonamides which are aspartyl protease inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention.
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(2008/06/13)