- 4-AMINO OR 4-ALKOXY-SUBSTITUTED ARYL SULFONAMIDE COMPOUNDS WITH SELECTIVE ACTIVITY IN VOLTAGE-GATED SODIUM CHANNELS
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Disclosed are compounds of Formula (I), Formula (II), or a salt thereof: Formula (I) Formula (II) which compounds have properties for inhibiting Nav 1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula (I), Formula (II) or their salts, and methods of treating pain disorders, cough, and itch using the same.
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Page/Page column 58
(2020/07/05)
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- METHYL DIAZEPANE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to methyl diazepane compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 32
(2016/06/14)
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- Design and synthesis of optically pure 3-aryl-6-methyl-2- thioxotetrahydropyrimidin-4(1H)-ones as anti-prostate cancer agents
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3-Aryl-6-methyl-2-thioxotetrahydropyrimidin-4(1H)-ones were proposed as a new class of anti-prostate cancer agents on the basis of molecular modeling studies. Stereoselective synthesis of 3-aryl-6-methyl-2- thioxotetrahydropyrimidin-4(1H)-one derivatives was achieved by chiral induction employing (R)/(S)-α-methyl benzylamine and subsequent debenzylation with HBr in AcOH afforded the desired enantiomers in good yields. The compounds were screened in vitro against prostate cancer cell lines, PC-3 and LNCaP and the most potent derivatives were identified. the Partner Organisations 2014.
- Kumar, Varun,Rachamalla, Mahesh,Nandekar, Prajwal,Khatik, Gopal L.,Sangamwar, Abhay T.,Tikoo, Kulbhushan,Nair, Vipin A.
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p. 37868 - 37877
(2014/11/07)
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- Design and synthesis of optically pure 3-aryl-6-methyl-2-thioxotetrahydropyrimidin-4(1H)-ones as anti-prostate cancer agents
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3-Aryl-6-methyl-2-thioxotetrahydropyrimidin-4(1H)-ones were proposed as a new class of anti-prostate cancer agents on the basis of molecular modeling studies. Stereoselective synthesis of 3-aryl-6-methyl-2-thioxotetrahydropyrimidin-4(1H)-one derivatives was achieved by chiral induction employing (R)/(S)-α-methyl benzylamine and subsequent debenzylation with HBr in AcOH afforded the desired enantiomers in good yields. The compounds were screened in vitro against prostate cancer cell lines, PC-3 and LNCaP and the most potent derivatives were identified. This journal is
- Kumar, Varun,Rachamalla, Mahesh,Nandekar, Prajwal,Khatik, Gopal L.,Sangamwar, Abhay T.,Tikoo, Kulbhushan,Nair, Vipin A.
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p. 37868 - 37877
(2014/12/11)
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- Access to 2,6-disubstituted piperidines: Control of the diastereoselectivity, scope, and limitations. applications to the stereoselective synthesis of (-)-solenopsine A and alkaloid (+)-241D
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Scope and limitations in the diastereoselective preparation of 2,6-cis or 2,6-trans disubstituted piperidines are described, through intramolecular reaction of chiral β′-carbamate-α,β-unsaturated ketone. This methodology has been applied to the total synthesis of a few well chosen examples, such as (-)-solenopsine A and alkaloid (+)-241D.
- Abrunhosa-Thomas, Isabelle,Plas, Aurelie,Vogrig, Alexandre,Kandepedu, Nishanth,Chalard, Pierre,Troin, Yves
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p. 2511 - 2526
(2013/04/24)
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- Stereoselective synthesis and in vivo evaluation of the analgesic activity of polysubstituted bispidines
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Hetero-Michael addition on a chiral β'-amino α,β- unsaturated ketone gave, after some structural modifications, β,β'-diamino ketals. Mannich-type reactions of these diamines with an aldehyde led, with high diastereoselectivity, to trisubstituted piperidines. Another highly stereoselective Mannich cyclization, with an N-acyliminium ion generated in situ from the corresponding imide, allowed the preparation of original polycyclic bispidine derivatives. The antinociceptive effect of the three compounds prepared was evaluated in vivo by using the writhing test. If the biological results for the analgesic properties were disappointing, compared with the bispidine HZ2, which has a high affinity for opioid receptors, the modularity of the approach offered the possibility of introducing many substituents for new applications, which was promising because the bispidine core has been described to have many different activities. Total stereoselective synthesis of bispidine derivatives is achieved by using as two successive Mannich reactions key steps. This process constitutes a powerful approach toward the preparation of a polycyclic bispidine backbone with high enantioselectivity.
- Plas, Aurelie,Troin, Yves,Chalard, Pierre,Marchand, Fabien,Eschalier, Alain
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supporting information
p. 6070 - 6079,10
(2020/09/02)
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- Homochiral lithium amides for the asymmetric synthesis of β-amino acids
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Secondary homochiral lithium amides derived from α-methylbenzylamine undergo highly diastereoselective conjugate additions to a range of α,β-unsaturated esters. The corresponding β-amino acids are readily liberated by successive N-debenzylation and ester hydrolysis, furnishing (R)-β-amino butyric acid, (R)-β-amino pentanoic acid, (S)-β-leucine, (R)-β-amino octanoic acid, (S)-β-phenylalanine, (S)-β-tyrosine methyl ether, (S)-β-tyrosine hydrochloride and (S)-β-(2-methoxyphenyl)-β-amino propanoic acid in high yields and high ee. The application of this procedure to the synthesis of the natural products (R)-β-DOPA and (R)-β-lysine is demonstrated. The development of a simplified one-pot reaction protocol applicable to the multi-gram scale synthesis of homochiral β-amino esters is also delineated.
- Davies, Stephen G.,Garrido, Narciso M.,Kruchinin, Dennis,Ichihara, Osamu,Kotchie, Luke J.,Price, Paul D.,Mortimer, Anne J. Price,Russell, Angela J.,Smith, Andrew D.
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p. 1793 - 1811
(2007/10/03)
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- Asymmetric Synthesis of anti-α-Alkyl-β-amino Acids
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An investigation into the asymmetric induction accompanying alkylations of enolates derived from the highly diastereoselective conjugate addition of lithium (R)-N-benzyl-N-α-methylbenzylamide (R)-1 to crotonate and cinnamate esters has been performed.The
- Davies, Stephen G.,Walters, Iain A. S.
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p. 1129 - 1140
(2007/10/02)
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- Enantioselective Synthesis of β-Amino Acids. 5. Stereoselective Reaction of Chiral Pyrimidinone Enolates with Aldehydes
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Hydro-pyrimidinones ((2S,6R)-3) and ((2S)-6) were prepared from methyl crotonate via 3-aminobutanoate, and their corresponding lithium enolate and dienolate derivatives were added to various aldehydes.The high regio- and stereoselectivities observed in these aldol reactions pave the road for the preparation of enantiomerically pure β-hydroxy-β'-amino acids.The structures of the products were confirmed by X-ray crystal structure analysis (eight examples).
- Murer, Peter,Rheiner, Beat,Juaristi, Eusebio,Seebach, Dieter
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p. 319 - 344
(2007/10/02)
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- ASYMMETRIC SYNTHESIS OF R-β-AMINO BUTANOIC ACID AND S-β-TYROSINE: HOMOCHIRAL LITHIUM AMIDE EQUIVALENTS FOR MICHAEL ADDITIONS TO α,β-UNSATURATED ESTERS.
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Michael addition of the lithium amide derived from R-N-(α-methylbenzyl)benzylamine to benzyl E-crotonate is highly stereoselective (95percent d.e.) giving after debenzylation and crystallisation homochiral R-β-amino butanoic acid.A similar addition to methyl E-(p-benzyloxy)cinnamate is completely stereoselective giving after debenzylation and acid hydrolysis homochiral S-β-tyrosine as its HCl salt.
- Davies, Stephen G.,Ichihara, Osamu
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p. 183 - 186
(2007/10/02)
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