- Novel sulfonamide-based carbamates as selective inhibitors of bche
-
A series of 14 target benzyl [2-(arylsulfamoyl)-1-substituted-ethyl]carbamates was prepared by multi-step synthesis and characterized. All the final compounds were tested for their abil-ity to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase
- ?těpánková, ?árka,Enriz, Ricardo D.,Garro, Adriana D.,Ho?ek, Jan,Imramovsky, Ale?,Jampílek, Josef,Jendrzejewska, Izabela,Magar, Pratibha,Parravicini, Oscar,Pauk, Karel,Svr?ková, Katarina
-
-
- SuFExable Isocyanides for Ugi Reaction: Synthesis of Sulfonyl Fluoro Peptides
-
Herein, the sulfonyl fluoro isocyanides were first developed as a new type of SuFExable synthon, and they are used as building blocks in the Ugi reaction (U-4CR). The Ugi reaction was established and the substrate scope was investigated, and various sulfonyl fluoro α-amino amides and peptides could be reached in a one-step synthesis. Therefore, this protocol opens a new vision for SuFExable building blocks and click chemistry, and it also provides a distinct approach to sulfonyl fluoro peptides.
- Xu, Shuheng,Cui, Sunliang
-
supporting information
p. 5197 - 5202
(2021/07/20)
-
- RHO KINASE INHIBITOR, METHOD FOR PREPARING SAME AND USES THEREOF
-
Provided are a Rho kinase inhibitor, a method for preparing same and the uses thereof. The Rho kinase inhibitor designates a compound of Formula I, a stereoisomer thereof or pharmaceutically acceptable salt thereof. The Rho kinase inhibitor promotes endothelial cells and endothelin expression, prostenin expression, and vascular factors NO synthesis and secretion, has a promoting effect on proprostin expression independently of the doses used, shows lower toxicity, while being safer.
- -
-
Paragraph 0115
(2021/09/16)
-
- Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
-
α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenrichedN-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.
- Cheng, Jiang-Tao,Dong, Xiao-Yang,Gu, Qiang-Shuai,Li, Zhong-Liang,Liu, Juan,Liu, Xin-Yuan,Luan, Cheng,Wang, Fu-Li,Wang, Li-Lei,Yang, Ning-Yuan,Zhang, Yu-Feng
-
supporting information
p. 15413 - 15419
(2021/09/30)
-
- Chiral pyrazole derivative and synthesis method thereof
-
The invention belongs to the technical field of organic synthesis, and discloses a chiral pyrazole derivative and a synthesis method thereof. The chiral pyrazole derivative is (1-(4'-amino-5'-carbamoyl-1'-pyrazolyl)-(S)-2-propyl-benzyloxy amide. The synth
- -
-
Paragraph 0027-0029; 0040-0042; 0053-0055
(2020/06/20)
-
- Discovery of substituted 3H-pyrido[2,3-d]pyrimidin-4-ones as potent, biased, and orally bioavailable sst2 agonist
-
The discovery of a novel 3H-pyrido[2,3-d]pyrimidin-4-one series as potent and biased sst2 agonists is described. This class of molecules exhibits excellent sst2 potency and selectivity against sst1, sst3, and sst5 receptors, and they are significantly more potent at inhibiting cAMP production than inducing internalization. The orally bioavailable 6-(3-chloro-5-methylphenyl)-3-(3-fluoro-5-hydroxyphenyl)-5-({methyl[(2S)-pyrrolidin-2-ylmethyl]amino}methyl)-3H,4H-pyrido[2,3-d]pyrimidin-4-one (36) also suppresses GH secretion in GHRH-challenged rats in a dose-dependent manner.
- Betz, Stephen F.,Chen, Zhiyong,Kusnetzow, Ana Karin,Nguyen, Julie,Rico-Bautista, Elizabeth,Struthers, R. Scott,Tan, Hannah,Zhao, Jian,Zhu, Yunfei
-
supporting information
(2020/08/26)
-
- Stereoselective addition of Grignard reagents to sulfinimines derived from tartrate diol (threitol): Generation of chiral building blocks for the collective total synthesis of lentiginosine, conhydrine and methyldihydropalustramate
-
A systematic investigation of the addition of Grignard reagents to sulfinimines derived from tartaric acid diol was undertaken. It was observed that the chirality of the inherent tartrate moiety influences the diastereoselectivity of the resultant sulfinamides formed in the reaction. The formed products serve as excellent building blocks for the synthesis of natural products. This has been demonstrated in the collective total synthesis of lentiginosine, (+)-α-conhydrine and methyldihydropalustramate.
- Prasad, Kavirayani R.,Rangari, Vipin Ashok
-
-
- Synthesis of chiral nine and twelve-membered cyclic polyamines from natural building blocks
-
A rational strategy for the facile and efficient cyclization of amino acid-based linear precursors forming nine and twelve-membered cyclic peptidomimetics is reported. The resulting chiral lactams can readily be reduced to substituted cyclic polyamine ana
- Müntener, Thomas,Thommen, Fabienne,Joss, Daniel,Kottelat, Jérémy,Prescimone, Alessandro,H?ussinger, Daniel
-
supporting information
p. 4715 - 4718
(2019/05/02)
-
- Staudinger/aza-Wittig reaction to access Nβ-protected amino alkyl isothiocyanates
-
A unified approach to access Nβ-protected amino alkyl isothiocyanates using Nβ-protected amino alkyl azides through a general strategy of Staudinger/aza-Wittig reaction is described. The type of protocol used to access isothiocyanates depends on the availability of precursors and also, especially in the amino acid chemistry, on the behavior of other labile groups towards the reagents used in the protocols; fortunately, we were not concerned about both these factors as precursor-azides were prepared easily by standard protocols, and the present protocol can pave the way for accessing title compounds without affecting Boc, Cbz and Fmoc protecting groups, and benzyl and tertiary butyl groups in the side chains. The present strategy eliminates the need for the use of amines to obtain title compounds and thus, this method is step-economical; additional advantages include retention of chirality, convenient handling and easy purification. A few hitherto unreported compounds were also prepared, and all final compounds were completely characterized by IR, mass, optical rotation, and 1H and 13C NMR studies.
- Santhosh,Durgamma,Shekharappa,Sureshbabu, Vommina V.
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p. 4874 - 4880
(2018/07/15)
-
- Synthesis and evaluation of chirally defined side chain variants of 7-chloro-4-aminoquinoline to overcome drug resistance in malaria chemotherapy
-
A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methyl-piperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.
- Dola, Vasantha Rao,Soni, Awakash,Agarwal, Pooja,Ahmad, Hafsa,Raju, Kanumuri Siva Rama,Rashid, Mamunur,Wahajuddin, Muhammad,Srivastava, Kumkum,Haq,Dwivedi,Puri,Katti
-
-
- A Simple, efficient, Catalyst-Free and Solvent-Less Microwave-Assisted process for N-Cbz Protection of Several amines
-
A simple, green and chemo-selective method for the N-benzyloxycarbonylation of amines, β-amino alcohols, α-amino esters and sulfonamides has been developed under microwave irradiation. Good to excellent yields of the N-benzyloxy-carbamates compounds were obtained in short times without any side products.
- Aouf, Zineb,Mansouri, Rachida,Lakrout, Salah,Berredjem, Malika,Aouf, Nour-Eddine
-
p. 151 - 156
(2017/08/02)
-
- A rapid and efficient one-pot method for the reduction of N-protected α-amino acids to chiral α-amino aldehydes using CDI/DIBAL-H
-
N-Protected amino acids can be easily converted into chiral α-amino aldehydes in a one-pot reaction by activation with CDI followed by reduction with DIBAL-H. This method delivers Boc-, Cbz- and Fmoc-protected amino aldehydes from proteinogenic amino acids in very good isolated yields and complete stereointegrity.
- Ivkovic, Jakov,Lembacher-Fadum, Christian,Breinbauer, Rolf
-
p. 10456 - 10460
(2015/11/10)
-
- Synthesis of Nα-Z protected amino alkyl triazole acids and their application to neo-glycopeptides synthesis
-
The synthesis of triazole linked glycopeptides employing 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) mediated coupling of Z-protected triazole acids with glycosyl amines and amino acid esters is described. The coupling proceeded smoothly at room temperat
- Madhu, Chilakapati,Panguluri, Nageswara Rao,Sureshbabu, Vommina V.
-
p. 858 - 864
(2014/08/05)
-
- IOP-lowering effect of isoquinoline-5-sulfonamide compounds in ocular normotensive monkeys
-
Rho-associated coiled coil-formed protein kinase (ROCK) inhibitors are under development as a new class of antiglaucoma agents. Based on the potent ROCK inhibitor H-1152, previously developed by us, we explored the possibility of related compounds as anti
- Sumi, Kengo,Inoue, Yoshihiro,Nishio, Masahiro,Naito, Yasuhito,Hosoya, Takamitsu,Suzuki, Masaaki,Hidaka, Hiroyoshi
-
p. 831 - 834
(2014/02/14)
-
- Efficient access to enantiopure γ4-amino acids with proteinogenic side-chains and structural investigation of γ4- asn and γ4-ser in hybrid peptide helices
-
Hybrid peptides composed of α- and β-amino acids have recently emerged as new class of peptide foldamers. Comparatively, γ- and hybrid γ-peptides composed of γ4-amino acids are less studied than their β-counterparts. However, recent investigations reveal that γ4-amino acids have a higher propensity to fold into ordered helical structures. As amino acid side-chain functional groups play a crucial role in the biological context, the objective of this study was to investigate efficient synthesis of γ4-residues with functional proteinogenic side-chains and their structural analysis in hybrid-peptide sequences. Here, the efficient and enantiopure synthesis of various N- and C-terminal free-γ4-residues, starting from the benzyl esters (COOBzl) of N-Cbz-protected (E)-α,β-unsaturated γ-amino acids through multiple hydrogenolysis and double-bond reduction in a single-pot catalytic hydrogenation is reported. The crystal conformations of eight unprotected γ4-amino acids (γ4-Val, γ4-Leu, γ4-Ile, γ4-Thr(OtBu), γ4-Tyr, γ4-Asp(OtBu), γ4- Glu(OtBu), and γ-Aib) reveals that these amino acids adopted a helix favoring gauche conformations along the central Cγi￡ Cβ bond. To study the behavior of γ4- residues with functional side chains in peptide sequences, two short hybrid γ-peptides P1 (Ac-Aib-γ4-Asn-Aib-γ4-Leu- Aib-γ4-Leu-CONH2) and P2 (Ac-Aib- γ4-Ser-Aib-γ4-Val-Aib-γ4-Val- CONH2) were designed, synthesized on solid phase, and their 12-helical conformation in single crystals were studied. Remarkably, the γ4-Asn residue in P1 facilitates the tetrameric helical aggregations through interhelical H bonding between the side-chain amide groups. Furthermore, the hydroxyl side-chain of γ4-Ser in P2 is involved in the interhelical H bonding with the backbone amide group. In addition, the analysis of 87 γ4-residues in peptide single-crystals reveal that the γ4-residues in 12-helices are more ordered as compared with the 10/12- and 12/14-helices. Copyright
- Jadhav, Sandip V.,Misra, Rajkumar,Singh, Sumeet K.,Gopi, Hosahudya N.
-
supporting information
p. 16256 - 16262
(2013/12/04)
-
- A mild multistep conversion of n-protected α-amino acids into N-protected β3-amino acids utilizing the Nef reaction
-
Current methods of homologation of α-amino acids to β-amino acids have limitations. To overcome these shortfalls the Nef reaction has been utilized in the multistep synthesis of β3-amino acids from α-amino acids. In this approach, N-protected a
- Sleebs, Brad E.,Nguyen, Nghi H.,Hughes, Andrew B.
-
p. 747 - 751
(2013/05/08)
-
- NOVEL PRODUCTION METHOD FOR ISOQUINOLINE DERIVATIVES AND SALTS THEREOF
-
The present invention provides a method capable of industrially producing a target product, i.e., a compound represented by the aforementioned formula (I) or a salt thereof, which is useful for preventing and treating cerebrovascular disorders such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral edema, particularly for preventing and treating glaucoma, at high yield even on a large scale without imposing a negative impact on the environment. The present invention provides a method for producing a compound represented by formula (I) or a salt thereof, wherein the method comprises a step of reacting a compound represented by formula (III) or a salt thereof with a compound represented by formula (II) in the presence of at least one solvent selected from the group consisting of a nitrile solvent, an amide solvent, a sulfoxide solvent, and a urea solvent, and a base.
- -
-
Paragraph 0103; 0104
(2013/06/26)
-
- An expedient route for the reduction of carboxylic acids to alcohols employing 1-propanephosphonic acid cyclic anhydride as acid activator
-
A simple and efficient method for the synthesis of alcohols from the corresponding carboxylic acids is described. Activation of carboxylic acid with 1-propane phosphonic acid cyclic anhydride (T3P) and subsequent reduction of the intermediate phosphonic anhydride with NaBH4 yield the alcohol in excellent yields with good purity in less duration. Reduction of several alkyl/aryl carboxylic acids and Nα-protected amino acids/peptide acids as well as Nβ-protected amino acids was successfully carried out to obtain corresponding alcohols in good yields and the products characterized. The procedure is mild, safe, simple and the isolation of the products is easy.
- Nagendra,Madhu,Vishwanatha,Sureshbabu, Vommina V.
-
experimental part
p. 5059 - 5063
(2012/09/22)
-
- Novel diamide insecticides: Sulfoximines, sulfonimidamides and other new sulfonimidoyl derivatives
-
Novel insecticidal anthranilamides with elaborated sulfur-containing groups are described. The synthesis of compounds with functional groups such as sulfoximines and scarcely reported groups such as sulfonimidoyl hydrazides and hydroxylamides, their in vitro and in vivo biological activity as well as their physical properties are reported.
- Gnamm, Christian,Jeanguenat, Andre,Dutton, Ana C.,Grimm, Christoph,Kloer, Daniel P.,Crossthwaite, Andrew J.
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scheme or table
p. 3800 - 3806
(2012/07/17)
-
- Synthesis of cyclic antifreeze glycopeptide and glycopeptoids and their ice recrystallization inhibition activity
-
Until now, few groups reported the antifreeze activity of cyclic glycopeptides; however, the tedious synthetic procedure is not amenable to study the intensive structure activity relationship. A series of N-linked cyclic glycopeptoids and glycopeptide have been prepared to evaluate antifreeze activity as a function of peptide backbone cyclization and methyl stereochemical effect on the rigid Thr position. This study has combined the cyclization protocol with solid phase peptide synthesis and obtained significant quantities of homogeneous cyclic glycopeptide and glycopeptoids. Analysis of antifreeze activity revealed that our cyclic peptide demonstrated RI activity while cyclic glycopeptoids showed no RI activity. These results suggest that the subtle changes in conformation and Thr orientation dramatically influence RI activity of N-linked glycopeptoids.
- Ahn, Mija,Murugan, Ravichandran N.,Shin, Song Yub,Kim, Eunjung,Lee, Jun Hyuck,Kim, Hak Jun,Bang, Jeong Kyu
-
p. 3565 - 3570
(2013/01/16)
-
- An efficient and facile synthesis of N-Cbz-β-aminoalkanesulfonamides
-
An efficient method for the synthesis of N-Cbz-β- aminoalkanesulfonamides was described. N-Cbz-β-aminoalkanesulfona-mides were readily prepared in good yields from a variety of amino alcohols, including optically active ones, via N-Cbz protection with ben
- Meng, Fanhua,Chen, Ning,Xu, Jiaxi
-
p. 2548 - 2553
(2013/06/27)
-
- Synthesis and biological evaluation of novel irreversible serine protease inhibitors using amino acid based sulfonyl fluorides as an electrophilic trap
-
We have designed and synthesized novel irreversible serine protease inhibitors containing aliphatic sulfonyl fluorides as an electrophilic trap. These substituted taurine sulfonyl fluorides derived from taurine or protected amino acids were conveniently s
- Brouwer, Arwin J.,Ceylan, Tarik,Jonker, Anika M.,Linden, Tima Van Der,Liskamp, Rob M.J.
-
p. 2397 - 2406
(2011/05/12)
-
- Simple methodology for the preparation of amino alcohols from amino acid esters using nabh4-methanol in THF
-
Amino alcohols constitute a very useful and versatile class of organic compounds, with important applications in synthetic and medicinal chemistry. However, in most of the procedures described in the literature for the obtainment of these compounds, considerable limitations can be found, such as drastic conditions, long time reactions, poor yields, and purification problems. The present article describes a methodology that gives amino alcohols and N-protected amino alcohols based on the reduction of amino acid esters under mild conditions, employing NaBH4 in the presence of methanol. The reactions occurred in a short time (15-20min) and provide yields of 50-95%.
- Goncalves,Pinheiro,Da Silva,Da Costa,Kaiser,De Souza
-
experimental part
p. 1276 - 1281
(2011/05/04)
-
- Enantioselective hydroformylation of N-vinyl carboxamides, allyl carbamates, and allyl ethers using chiral diazaphospholane ligands
-
Rhodium complexes of diazaphospholane ligands catalyze the asymmetric hydroformylation of N-vinyl carboxamides, allyl ethers, and allyl carbamates; products include 1,2- and 1,3-aminoaldehydes and 1,3-alkoxyaldehydes. Using glass pressure bottles, short reaction times (generally less than 6 h), and low catalyst loading (commonly 0.5 mol %), 20 substrates are successfully converted to chiral aldehydes with useful regioselectivity and high enantioselectivity (up to 99% ee). Chiral Roche aldehyde is obtained with 97% ee from the hydroformylation of allyl silyl ethers. Commonly difficult substrates such as 1,1- and 1,2-disubstituted alkenes undergo effective hydroformylation with 89-97% ee and complete conversion for six examples. Palladium-catalyzed aerobic oxidative amination of allyl benzyl ether followed by enantioselective hydroformylation yields the β3-aminoaldehyde with 74% ee.
- McDonald, Richard I.,Wong, Gene W.,Neupane, Ram P.,Stahl, Shannon S.,Landis, Clark R.
-
supporting information; body text
p. 14027 - 14029
(2011/01/04)
-
- Simple and efficient synthesis of Fmoc/Boc/Cbz-protected-β-amino alcohols and peptidyl alcohols employing Boc2O
-
An efficient method for the activation of Fmoc/Boc/Cbz-protected amino acids using Boc2O and the reduction of the in situ generated carbonic-carbonic anhydride to their corresponding 1β-amino alcohols using sodium borohydride has been described. The method is simple, rapid and free from racemization. Besides, the protocol is also extended for the conversion of N-urethane protected peptide acids to their corresponding alcohols. Copyright
- Lalithamba,Sureshbabu, Vommina V.
-
experimental part
p. 1372 - 1378
(2011/01/13)
-
- Carbamate derivatives of felbamate as potential anticonvulsant agents
-
Several monocarbamate compounds derived from felbamate were synthesized and 11 target compounds (1, 4, and 6-14) were initially evaluated in mice MES and PTZ models in our laboratory. Carbamate compounds with varying substituents on the oxygen (1-4) gave anticonvulsant activity with a wide range of ED 50 in MES test from 300 mg/kg (4) and compounds with different groups on the nitrogen (5-14) also were quite active in the range of 15 mg/kg (14) to 170.5 mg/kg (6). This suggested that the spatial limitation in the MES model seemed flexible especially on the nitrogen end. All tested compounds showed some activity against mice scPTZ test, but none had the ED50 value 50 mg/kg. Ten selected compounds (1 and 6-14) for subsequent pharmacological evaluation in NIH all gave positive mice MES activity except 8 and 9, which were unexpectedly active in rats after further evaluations. Among the compounds, 1, 8, and 9 advanced to the quantitative study and 1 and 9 provided the highest PI values, 15 and 21, respectively, in the rat oral MES test.
- Kung, Ching-Hsin,Kwon, Chul-Hoon
-
experimental part
p. 498 - 513
(2011/03/19)
-
- Addition of allylzinc to a-amino acid-derived imines: Synthesis of diamino alcohols by Hydroboration
-
Imines obtained by condensation of Z-pro- tected or Boc-protected α-amino aldehydes with α-amino tert-butyl esters or with O-silyl-protected amino alcohols were reacted with preformed allyl zinc yielding homoal- lylamines with yields around 50% and selectivities ranging from 50:50 to 90:10. Hydroboration of the terminal double bond furnished diamino alcohols with yields up to 97%. The configuration of the substrates was determined by X-ray-crystallographic analysis of a hydroboration product and comparison of physical data. Springer-Verlag 2010.
- Virlouvet, Mickael,Goesmann, Helmut,Feldmann, Claus,Podlech, Joachim
-
experimental part
p. 177 - 198
(2010/08/05)
-
- Expedient solid-phase synthesis of both symmetric and asymmetric diol libraries targeting aspartic proteases
-
C2-symmetric diols have been shown to be highly potent against HIV-1 protease (PR). However, gaining access to these compounds has been hampered by the need of multistep solution-phase reactions which are often tedious and inefficient. In this Letter, we have disclosed a solid-phase strategy for rapid preparation of small molecule-based, symmetric and asymmetric diols as potential HIV-1 protease inhibitors. Upon biological screening, we found one of them, SYM-5, to be a potent and selective inhibitor (Ki = 400 nM) against HIV-1 protease.
- Shi, Haibin,Liu, Kai,Leong, Wendy W.Y.,Yao, Shao Q.
-
supporting information; experimental part
p. 3945 - 3948
(2010/03/30)
-
- Simple and rapid synthesis of Nα-urethane protected β-amino alcohols and peptide alcohols employing HATU
-
The activation of the Nα--urcihanc protected (Fmoc-/Boc-/Z-/Bsmoc) α-amino acids employing l-[bis(dimethylamino)- methylene]-lH-l,2,3-triazolo-[4,5-6]pyridinium.0hexa-flurophosphate-3-oxide (HATU) followed by reduction of the in situ generated -OAt ester with NaBH 4 results in the corresponding ss-amino alcohols in good yields. This synthesis is the first demonstration of the application of the efficient coupling agent HATU for practical synthesis of ss-amino alcohols. The protocol is general for all common N-protecting groups including the highly base sensitive Bsmoc group. The protocol has also been successfully extended for the synthesis of peptide alcohols.
- Surcshbabu, Vommina V.,Sudarshan,Chennakrishnareddy
-
experimental part
p. 574 - 579
(2009/12/06)
-
- Synthesis of β-aminoethanesulfonyl fluorides or 2-substituted taurine sulfonyl fluorides as potential protease inhibitors
-
Substituted taurine sulfonyl fluorides derived from taurine or protected amino acids are conveniently synthesized from β-aminoethanesulfonyl chlorides using KF/18-crown-6 or from β-aminoethanesulfonates using DAST.
- Brouwer, Arwin J.,Ceylan, Tarik,Linden, Tima van der,Liskamp, Rob M.J.
-
scheme or table
p. 3391 - 3393
(2009/09/05)
-
- SMALL MOLECULE BRADYKININ B1 RECEPTOR ANTAGONISTS
-
Disclosed are compounds of formula (I) which are bradykinin B1 receptor (B1R) antagonists. These compounds are useful to treat diseases or relieve adverse symptoms associated with inflammation and pain. The invention encompasses novel compounds and acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases involving inflammation and pain.
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-
Page/Page column 99-100
(2009/04/25)
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- Synthesis of novel N-protected β3-amino nitriles: study of their hydrolysis involving a nitrilase-catalyzed step
-
Several commercially available nitrilases were investigated with regard to their potential to hydrolyze N-protected β3-amino nitriles into their corresponding N-protected β3-amino acids. The biotransformations were obtained in different proportions depending on the nitrilase involved. The best hydrolysis results were achieved for the N-Cbz-β3-amino nitrile from l-alanine using the NIT-107, in a phosphate buffer at 0.05 M. However, no biotransformation into the corresponding acids was observed for the N-sulfonylamide β3-amino nitriles. Two simple and efficient procedures to prepare the β3-amino nitriles from their analogous α-amino acids are described. Thirty four new substances were synthesized and characterized over the course of this work.
- Veitia, Maite Sylla-Iyarreta,Brun, Pierre Louis,Jorda, Pierre,Falguieres, Annie,Ferroud, Clotilde
-
experimental part
p. 2077 - 2089
(2010/03/04)
-
- A mild and efficient chemoselective protection of amines as N-benzyloxycarbonyl derivatives in the presence of La(NO3)3·6H2O under solvent-free conditions
-
A facile and versatile method for the chemoselective N-benzyloxycarbonylation of amines has been developed by treatment with benzyloxycarbonyl chloride (Cbz-Cl) in the presence of lanthanum(III) nitrate hexahydrate under solvent-free conditions. The metho
- Chinni Mahesh,Narasimhulu,Srikanth Reddy,Suryakiran,Venkateswarlu
-
-
- Comparative approaches toward diamines containing spatially separated homobenzylic and benzylic nitrogen stereocenters
-
Several synthetic strategies to diamines 1-3 are described. The optimum approach via opening of aziridine afforded 1-3 in 29-60% yield over 3-5 steps. A study on formation of the benzylic stereocenter using Toste's rhenium-catalyzed asymmetric reduction of phosphinyl ketimines was also evaluated and afforded 15 in 92% de.
- Achmatowicz, Michal,Chan, Johann,Wheeler, Philip,Liu, Longbin,Faul, Margaret M.
-
p. 4825 - 4829
(2008/02/05)
-
- Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 3: Heterocyclic P3
-
A series of Nα-2-benzoxazolyl-α-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure-activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported.
- Tully, David C.,Liu, Hong,Alper, Phil B.,Chatterjee, Arnab K.,Epple, Robert,Roberts, Michael J.,Williams, Jennifer A.,Nguyen, Khanhlinh T.,Woodmansee, David H.,Tumanut, Christine,Li, Jun,Spraggon, Glen,Chang, Jonathan,Tuntland, Tove,Harris, Jennifer L.,Karanewsky, Donald S.
-
p. 1975 - 1980
(2007/10/03)
-
- Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers
-
The synthesis and structure-activity relationship of a series of arylaminoethyl amide cathepsin S inhibitors are reported. Optimization of P3 and P2 groups to improve overall physicochemical properties resulted in significant improvements in oral bioavail
- Tully, David C.,Liu, Hong,Chatterjee, Arnab K.,Alper, Phil B.,Epple, Robert,Williams, Jennifer A.,Roberts, Michael J.,Woodmansee, David H.,Masick, Brian T.,Tumanut, Christine,Li, Jun,Spraggon, Glen,Hornsby, Michael,Chang, Jonathan,Tuntland, Tove,Hollenbeck, Thomas,Gordon, Perry,Harris, Jennifer L.,Karanewsky, Donald S.
-
p. 5112 - 5117
(2007/10/03)
-
- NOVEL LYSOPHOSPHATIDIC ACID RECEPTOR SELECTIVE ANTAGONISTS
-
The present invention is directed to compositions comprising lysophosphatidic acid analogs and methods of using such analogs as agonist or antagonists of LPA receptor activity. In addition the invention is directed to LPA receptor agonists that vary in the degree of selectivity at individual LPA receptors (i.e. LPA1, LPA2 and LPA3). More particularly the present invention is directed to LPA analogs wherein the glycerol is replaced with ethanolamine and a variety of substitutions have been linked at the second carbon atom.
- -
-
Page/Page column 75
(2008/06/13)
-
- SULFONAMIDE DERIVATIVES, INSECTICIDES FOR AGRICULTURAL AND HORTICULTURAL USE, AND USAGE THEREOF
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Sulfonamide derivatives represented by general formula (I) or salts thereof; insecticides for agricultural and horticultural use containing the same as the active ingredient; and usage thereof: ???[wherein A is optionally substituted (C1-C6)alkylene, (C3-C6)alkenylene or the like; R1 is H, optionally substituted (C1-C6)alkyl, (C3-C6)alkenyl, (C3-C6)cycloalkyl or the like; R2, R3 and R4 are each H, (C1-C6)alkyl, (C3-C6)alkenyl or the like, or R2 and A or R2 and R1 may form a 3- to 8-membered ring which may be interrupted by one to three atoms selected from among O, S and N; Q is C or N; X and Y are each halogen, CN, NO2, (C1-C6)alkyl, (C2-C6)alkenyl or the like; m is 0 to 2; n is 0 to 3; and two adjacent Xs or Ys on the aromatic ring may be united to form a fused ring]. The compounds exhibit excellent insecticidal activity against insect pests resistant to existing pesticides even when applied in dosages lower than those of similar pesticides.
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Page/Page column 21
(2008/06/13)
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- New pyrrole-based amino acids for the synthesis of peptidomimetic constrained scaffolds
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A new family of pyrrole-based amino acids have been prepared through the microwave assisted Paal-Knorr reaction of 1-4 ketoesters derived from the corresponding β-ketoester with a functional homologation. The carboxylic group is located in position 3 of the pyrrole, whereas the amino group, protected with the Cbz moiety, is present on the side chain in positions 1 or 2. These compounds were used to prepare constrained oligopeptides.
- Alongi, Maddalena,Minetto, Giacomo,Taddei, Maurizio
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p. 7069 - 7072
(2007/10/03)
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- 1-Methylcarbapenem derivatives
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1-Methylcarbapenem compounds having antibacterial activity, pharmacologically acceptable esters or salts thereof and pharmaceutical compositions (particularly antibacterial agents) containing them as an active ingredient are described. In addition, the invention includes the use of these compounds, ester derivatives or salts for the manufacture of pharmaceutical compositions, or a method for the prevention or treatment of diseases (particularly bacterial infections) by administering a pharmacologically effective amount of the compounds, ester derivatives or salts to warm-blooded animals (particularly human beings).
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Page/Page column 140
(2010/02/05)
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- Stereoselective Aldol Additions Catalyzed by Dihydroxyacetone Phosphate-Dependent Aldolases in Emulsion Systems: Preparation and Structural Characterization of Linear and Cyclic Iminopolyols from Aminoaldehydes
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The potential of dihydroxyacetone phosphate (DHAP)-dependent aldolases to catalyze stereoselective aldol additions is, in many instances, limited by the solubility of the acceptor aldehyde in aqueous/co-solvent mixtures. Herein, we demonstrate the efficiency of emulsion systems as reaction media for the class I fructose-1,6-b isphosphate aldolase (RAMA) and class II recombinant rhamnulose-1-phosphate aldolase from E. coli (RhuA)catalyzed aldol addition between DHAP and N-benzyloxycarbonyl (N-Cbz) aminoaldehydes. The use of emulsions improved the RAMA-catalyzed aldol conversions by three to tenfold relative to those in conventional DMF/ water mixtures. RhuA was more reactive than RAMA towards the N-Cbz aminoaldehydes regardless of the reaction medium. With (S)- or (R)-Cbz-alaninal, RAMA exhibited preference for the R enantiomer, while RhuA had no enantiomeric discrimination. The linear N-Cbz aminopolyols thus obtained were submitted to catalytic intramolecular reductive amination to afford the corresponding iminocyclitols. This reaction was diastereoselective in all cases examined; the face selectivity was controlled by the stereochemistry of the newly formed hydroxyl group originating from the aldehyde. Characterization of the resulting iminocyclitols allowed the assessment of the diastereoselectivity of the enzymatic aldol reactions with respect to the N-protected aminoaldehyde. RAMA formed single diastereoisomers from N-Cbz-glycinal and from both enantiomers of N-Cbz-alaninal, while 14% of the epimeric product was observed from N-Cbz-3-aminopropanal. Diastereoselectivity from RhuA was lower than that observed from RAMA. Interestingly, a single diastereoisomer was formed from (S)-Cbz-alaninal, whereas only a 34% diastereomeric excess was observed from its enantiomer (i.e., (R)-Cbz-alaninal).
- Espelt, Laia,Parella, Teodor,Bujons, Jordi,Solans, Conxita,Joglar, Jesus,Delgado, Antonio,Clapes, Pere
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p. 4887 - 4899
(2007/10/03)
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- ACYLHYDRAZINE DERIVATIVES, PROCESS FOR PREPARING THE SAME AND USE THEREOF
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Novel acylhydrazine derivatives exhibiting an inhibitory activity against activated blood coagulation factor X, which are compounds of general formula (I)or salts thereof, wherein R is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; R1and R2are each hydrogen or optionally substituted hydrocarbyl, or alternatively R1and R2or the substituent of X1and R2may be united to form an optionally substituted ring; X1and X2are each free valency, optionally substituted alkylene, or optionally substituted imino; D is oxygen or sulfur; A is -N(R3)-Y- or -N=Y-, R3is hydrogen, optionally substituted hydrocarbyl, or acyl; Y is an optionally substituted chain hydrocarbon group or an optionally substituted cyclic group; and Z is (1) optionally substituted amino, (2) optionally substituted imidoyl, or (3) an optionally substituted nitrogenous heterocycle group.
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- Effective and mild method for preparation of optically active α-amino aldehydes via TEMPO oxidation
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The TEMPO oxidation method is successfully applied to preparation of variously protected, optically active α-amino aldehydes without racemization and in very good yield.
- Jurczak, Janusz,Gryko, Dorota,Kobrzycka, Elzbieta,Gruza, Henryk,Prokopowicz, Piotr
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p. 6051 - 6064
(2007/10/03)
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- Synthesis of optically active imidazolines, azapenams, dioxocyclams, and bis-dioxocyclams
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Optically active 4-methyl-4-carbomethoxy-Δ2-imidazoline was efficiently synthesized on a multigram scale. Photolysis with (methoxymethylcarbene)chromium complex produced the optically active azapenam in good yield and with high stereoselectivity. Acid-catalyzed dimerization followed by reduction produced the corresponding optically active dioxocyclam in good yield. Using a bis-carbene complex, an optically active bis-dioxocyclam was produced in excellent yield.
- Hsiao, Yi,Hegedus, Louis S.
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p. 3586 - 3591
(2007/10/03)
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- Thiazolidine and oxazolidine derivatives, their preparation and their medical use
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Compounds of formula (I): STR1 and salts, esters and solyates thereof and pro-drugs therefor are useful for the treatment and/or prophylaxis of a variety of disorders, including one or more of: hyperlipemia, hyperglycemia, obesity, glucose tolerance insufficiency, insulin resistance and diabetic complications.
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- Synthesis of enantiopure N-and C-protected homo-β-amino acids by direct homologation of α-amino acids
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Enantiopure N-and/or C-protected homo-β-amino acids are prepared readily and in good yields from N-protected α-amino acids with the same side chain, via reduction of the carboxyl function and conversion of the resulting N-protected β-amino alcohol into the corresponding β-amino iodide and then β-amino cyanide. The key step of this strategy is represented by the synthesis of the enantiopure N-protected β-amino iodides 2 and 3 that are smoothly obtained from the parent amino alcohols 1 by polymer bound triarylphosphine-I2 complex in anhydrous dichloromethane.
- Caputo, Romualdo,Cassano, Ersilia,Longobardo, Luigi,Palumbo, Giovanni
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p. 12337 - 12350
(2007/10/02)
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- Chiral N-Protected β-Iodoamines from α-Aminoacids: a General Synthesis
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N-Protected D- or L-β-iodoamines (as 2), which are useful intermediates for the preparation of chiral β-aminoacids, are obtained smoothly from β-aminols (as 1) in two steps and high yields.
- Caputo, Romualdo,Cassano, Ersilia,Longobardo, Luigi,Palumbo, Giovanni
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p. 167 - 168
(2007/10/02)
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- Pinacol cross coupling of 2-[N-(alkoxycarbonyl)amino] aldehydes and aliphatic aldehydes by [V2Cl3(THF)6]2[Zn2Cl 6]. Synthesis of syn,syn-3-[N-(alkoxycarbonyl)amino] 1,2-diols
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Slow addition of 2-[N-(alkoxycarbonyl)amino] aldehydes to mixtures of [V2Cl3(THF)6]2[Zn2Cl 6] and aliphatic aldehydes gave syn,syn-3-[N-(alkoxycarbonyl)amino] 1,2-diols in good yield and high enantiomeric purity (>99:1). The alkyl group of the N-alkoxycarbonyl was shown to influence the yield: Me > allyl > Bn > t-Bu. Only the syn,syn diastereomer was observed (>20:1), except with N-Cbz-alaninal (10:1:1), O-benzyl-N-Cbz-serinal (7:1), and N-Cbz-prolinal (5:1 to 12:1). A new serinai derivative, N-Cbz-O-TBS-serinal, was cross coupled with n-pentadecanal to give a derivative of xylo-D-C18-phytosphingosine.
- Konradi, Andrei W.,Kemp, Scott J.,Pedersen, Steven F.
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p. 1316 - 1323
(2007/10/02)
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- Absolute configuration of the solenopsins, venom alkaloids of the fire ants
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An effective and practical procedure has been developed that allows the assignment of the absolute configuration of solenopsins from diverse origins using only small amounts of material. The method is based on the transformation of the natural secondary amines into diastereoisomeric amides by reaction with (R)-2-methoxy-2-phenyl-2-(trifluoromethyl)acetic acid chloride (MTPA-Cl), followed by comparison of their chromatographic behaviour with those of standards of established absolute configuration. This procedure has been applied to three samples of ants: Solenopsis geminata workers, S. invicta workers and S. invicta alates. It has been found that the absolute configuration of the trans alkaloids is always (2R,6R) while that of the cis alkaloids is (2R,6S). Moreover, a new synthesis of enantiomerically pure solenopsin A (4) and isosolenopsin A (3) starting from L-alanine is presented.
- Leclercq,Thirionet,Broeders,Daloze,Vander Meer,Braekman
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p. 8465 - 8478
(2007/10/02)
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- The Influence of Protecting Group Character on the Diastereoselectivity of Thiazolidine Ring Formation from Amino Aldehydes and Cysteine
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A series of 2-(1'-aminoalkyl)-thiazolidine-4-carboxylic acid derivatives was synthesized by condensation of (R)- or (S)-Cys with the amino aldehydes obtained from N-Boc-protected (S)-Ile, (S)-Leu, O-Bzl-(S)-Tyr, (S)- and (R)-Phe, and N-Z-(S)-Phe, N-Pht-(S)-Phe and N-(Pht)-(R)-Phe. All compounds were studied by 1H NMR and CD. The 2D NOESY experiments were carried out to determine the configuration of the newly formed stereogenic centre in position 2 of the thiazolidine ring. It was found that the configuration on the thiazolidine C2 atom is R or S when N-Boc- and N-Z-(S)-amino aldehydes or N-Boc- and N-Z-(R)-amino aldehydes are used in the reaction, respectively. The situation is opposite in the case of N-Pht-Phe derived amino aldehydes. The relation between the C2 atom configuration and the shape of CD spectra is discussed. Key words: 2-(1'-aminoalkyl)-thiazolidine-4-carboxylic acids, amino aldehydes, cysteine, stereoselectivity, absolute configuration, NMR, CD.
- Wyslouch, Aleksandra,Lisowski, Marek,Siemion, Ignacy Z.
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p. 117 - 130
(2007/10/02)
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