- Two-way homologation of aliphatic aldehydes: Both one-carbon shortening and lengthening via the same intermediate
-
Aliphatic aldehydes can be homologated to both one-carbon shorter and one-carbon longer homologous carbonyl compounds through the 2–4 steps of reactions via the same intermediates, β,γ-unsaturated α-nitrosulfones, prepared from the proline-catalyzed sequential reactions of several aliphatic aldehydes with phenylsulfonylnitromethane. While the oxidative cleavage of the key intermediates gave one-carbon less homologous carbonyl compounds, the reduction of the same key intermediates followed by an oxidation produced one-carbon more homologous carbonyl compounds.
- Yoo, Jae Won,Seo, Youngran,Park, Jong Beom,Kim, Young Gyu
-
-
- 1,3,4,9-TETRAHYDRO-2H-PYRIDO[3,4-B]INDOLE DERIVATIVE COMPOUNDS AND USES THEREOF
-
The present invention relates to 1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole derivative compounds and uses thereof. In particular, compounds of the invention have antibacterial activity and/or are capable of re-sensitizing methicillin-resistant Staphylococcus aureus to a P-lactam antibiotic or a combination of a P-lactam antibiotic and a P-lactamase inhibitor. The present invention also relates to a method for producing and using said compounds.
- -
-
Paragraph 0075-0076
(2020/03/05)
-
- CARBOXAMIDES AS UBIQUITIN-SPECIFIC PROTEASE INHIBITORS
-
The present disclosure relates to modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25, pharmaceutical compositions comprising the inhibitors, and methods of using the inhibitors. The modulators, such as inhibitors, of at least one pathway chosen from USP28 and USP25 can be useful in the treatment of cancers, among other ailments.
- -
-
Paragraph 00301
(2019/02/25)
-
- α-Amino Aldehydes as Readily Available Chiral Aldehydes for Rh-Catalyzed Alkyne Hydroacylation
-
Readily available α-amino aldehydes, incorporating a methylthiomethyl (MTM) protecting group on nitrogen, are shown to be efficient substrates in Rh-catalyzed alkyne hydroacylation reactions. The reactions are performed under mild conditions, employing a small-bite-angle bis-phosphine ligand, allowing for good functional group tolerance with high stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched α-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.
- Hooper, Joel F.,Seo, Sangwon,Truscott, Fiona R.,Neuhaus, James D.,Willis, Michael C.
-
supporting information
p. 1630 - 1634
(2016/02/20)
-
- As the NS4B inhibitor benzofuran analogs (by machine translation)
-
The present invention discloses a kind of as NS4B benzofuran analogue inhibitors, in particular to the formula (I) below or a pharmaceutically acceptable salt thereof. (by machine translation)
- -
-
Paragraph 0442; 0444; 0445; 0446; 0447
(2016/10/31)
-
- TETRAHYDROPYRROLOTHIAZINE COMPOUNDS
-
The present invention provides a compound of Formula (I): wherein R is H or F; and A is:(A), (B), (C) or (D); or a pharmaceutically acceptable salt thereof.
- -
-
Page/Page column 12-13
(2014/09/29)
-
- Vinyl dihydropyrans and dihydrooxazines: Cyclizations of catalytic ruthenium carbenes derived from alkynals and alkynones
-
A novel synthesis of 2-vinyldihydropyrans and dihydro-1,4-oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles. Mechanistic aspects of the new cyclizations are discussed. Setting a trap: A novel synthesis of 2-vinyldihydropyrans and dihydro-1,4-oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles.
- Cambeiro, Fermin,Lopez, Susana,Varela, Jesus A.,Saa, Carlos
-
supporting information
p. 5959 - 5963
(2014/06/10)
-
- TETRAHYDROPYRROLOTHIAZINE COMPOUNDS
-
The present invention provides compounds of Formula I: wherein A is selected from the group consisting of; R1 is H or F; R2 is H, —CH2OH, C1-C3 alkyl, R3 is H, F, or CN; R4 is H, F; or CN; and R5 is H, —CH3, or —OCH3; or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0100; 0101
(2013/10/08)
-
- Protecting-group-free total synthesis of (-)-rhazinilam and (-)-rhazinicine using a gold-catalyzed cascade cyclization
-
'Rhaz'zmatazz: A total synthesis of (-)-rhazinilam and the first asymmetric total synthesis of (-)-rhazinicine were accomplished by using constructing the indolizinone core through the gold-catalyzed cyclization of a fully elaborated linear ynamide. The scope and generality of this cascade reaction for the construction of highly substituted indolizinones were also investigated. Copyright
- Sugimoto, Kenji,Toyoshima, Kazuki,Nonaka, Shiori,Kotaki, Kenta,Ueda, Hirofumi,Tokuyama, Hidetoshi
-
supporting information
p. 7168 - 7171
(2013/07/26)
-
- FUSED HETEROCYCLIC COMPOUNDS AS OREXIN RECEPTOR MODULATORS
-
Disubstituted 3,8-diaza-bicyclo[4.2.0]octane and 3,6-diazabicyclo [3.2.0]heptane compounds are described, which are useful as orexin receptor modulators. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.
- -
-
Page/Page column 57
(2011/05/06)
-
- FUSED HETEROCYCLIC COMPOUNDS AS OREXIN RECEPTOR MODULATORS
-
Certain disubstituted 3,8-diaza-bicyclo[4.2.0]octane and 3,6-diazabicyclo [3.2.0]heptane are described, which are useful as orexin inhibitors. Such compounds may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia.
- -
-
Page/Page column 47
(2011/05/06)
-
- Synthesis and structure-activity relationship studies of 3,6-diazabicyclo[3.2.0]heptanes as novel α4β2 nicotinic acetylcholine receptor selective agonists
-
A series of novel, potent neuronal nicotinic acetylcholine receptor (nAChR) ligands derived from 3,6-diazabicyclo[3.2.0]heptane have been synthesized and evaluated for binding affinity and agonist activity at the α4β2 nAChR subtype. Structure-activity relationship studies of these novel nAChR ligands focused on substitution effects on the pyridine ring, as well as stereo- and regiochemical influences of the 3,6-diazabicyclo[3.2.0]heptane core. Small 5-substituents on the pyridine ring had a modest impact on the binding affinities and functional activities. 6-Bromo, 6-chloro, and 6-methyl substituents on the pyridine ring led to increased binding affinities and improved functional activities. Most of the 6-N-pyridinyl-substituted 3,6-diazabicyclo[3.2.0]heptanes are selective for the α4β2 nAChR subtype. Compounds (1R,5S)-25, (1R,5S)-55, and (1R,5S)-56 were virtually inactive as agonists at the hα3β4 nAChR but retained potency and efficacy at the hα4β2 nAChR subtype. 3-N-Pyridinyl-substituted series demonstrated more complex SAR. (1R,5R)-39, (1R,5R)-41, and (1R,5R)-42 were found to be much more potent at the hα3β4 nAChR subtype, whereas (1R,5R)-38 and (1R,5R)-40 were very selective at the hα4β2 nAChR subtype. The SAR studies of these novel ligands led to the discovery of several compounds with interesting in vitro pharmacological profiles.
- Ji, Anguo,Schrimpf, Michael R.,Sippy, Kevin B.,Bunnelle, William H.,Li, Tao,Anderson, David J.,Faltynek, Connie,Surowy, Carol S.,Dyhring, Tino,Ahring, Philip K.,Meyer, Michael D.
-
p. 5493 - 5508
(2008/03/13)
-
- (1S,5S)-3-(5,6-dichloropyridin-3-YL)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate
-
The present invention relates to the salt (1S,5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate and to methods of preparing the salt.
- -
-
Page/Page column 7
(2008/06/13)
-
- Substituted diazabicycloakane derivatives
-
Compounds of formula (I) Z-Ar1—Ar2??(I) wherein Z is a diazabicyclic amine, Ar1 is a 5- or 6-membered aromatic ring, and Ar2 is selected from an unsubstituted or substituted 5-membered heteroaryl ring; an unsubstituted or substituted 6-membered heteroaryl ring; 3,4-(methylenedioxy)phenyl; and phenyl substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.
- -
-
Page/Page column 33
(2010/02/11)
-
- Substituted diazabicycloalkane derivatives
-
Compounds of formula (I) [in-line-formulae]Z-Ar1—Ar2??(I) [/in-line-formulae] wherein Z is a diazabicyclic amine, Ar1 is a 5- or 6-membered aromatic ring, and Ar2 is selected from the group consisting of an unsubstituted or substituted 5- or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.
- -
-
Page/Page column 28-29
(2010/02/11)
-
- Amino-substituted tricyclic derivatives and methods of use
-
Compounds of formula (I) wherein A and B are amine-substituted sidechains, Y1 and Y2 form various tricyclic cores, and Rx is an optional substituent. Compounds and compositions of formula (I) are contemplated as well as methods for treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands that encompass compounds of formula (I) and other tricyclic derivatives.
- -
-
Page/Page column 42
(2010/02/13)
-
- Amino-substituted tricyclic derivatives and methods of use
-
Compounds of formula (I) wherein A and B are amine-substituted sidechains, Y1 and Y2 form various tricyclic cores, Xa and Xb are C, CH, or N, as defined herein, and Rx is an optional substituent. Compounds and compositions of formula (I) are contemplated as well as methods for treating conditions or disorders prevented by or ameliorated by α7nAChR ligands that encompass compounds of formula (I) and other tricyclic derivatives. Methods of using amino-substituted tricyclic derivatives also are described herein.
- -
-
Page/Page column 47
(2010/02/14)
-
- (IS-5S)-3-(5,6-dichloro-3-pyridinyl-)-3,6-diazabicyclo[3.2.0]heptane is an effective analgesic agent
-
The present invention discloses (1S,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane and its use to treat pain and other disorders associated with the nicotinic acetylcholine receptor.
- -
-
-
- (1S,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane is an effective analgesic agent
-
The present invention discloses (1S,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane and its use to treat pain and other disorders associated with the nicotinic acetylcholine receptor.
- -
-
-
- The use of enantiomerically pure ketene dithioacetal bis(sulfoxides) in highly diastereoselective intramolecular nitrone cycloadditions. Application in the total synthesis of the beta-amino acid (-)-cispentacin and the first asymmetric synthesis of cis-(3R,4R)-4-amino-pyrrolidine-3-carboxylic acid.
-
Intramolecular 1,3-dipolar nitrone cycloaddition onto an enantiomerically pure ketene dithioacetal dioxide using a three-carbon tether gave the corresponding 5,5-disubstituted isoxazolidine as a single diastereomer in good yield. This reaction has been used as the key step in an asymmetric synthesis of the naturally occurring antibiotic, (-)-cispentacin. An asymmetric synthesis of 4-amino-pyrrolidine-3-carboxylic acid has also been carried out using the intramolecular nitrone cycloaddition as the stereocontrolling step.
- Aggarwal, Varinder K,Roseblade, Stephen,Alexander, Rikki
-
p. 684 - 691
(2007/10/03)
-
- Diazabicyclic central nervous system active agents
-
Compounds of formula I pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.
- -
-
-
- A convenient synthesis of indole-substituted 2-pyrrolidones and their cyclized derivatives
-
Condensation between indole, Meldrum's acid, and benzyloxycarbonylacetaldehyde or aminoacetaldehyde derivatives yielded trimolecular adducts 7a-c. The latter were cyclized to indole-substituted 2-pyrrolidones 15a-b or 3-aminopyrrolid-2-ones 18a-b, dependi
- Boisbrun, Michel,Jeannin, Laurent,Toupet, Loic,Laronze, Jean-Yves
-
p. 3051 - 3057
(2007/10/03)
-
- ENZYMATIC ALDOL CONDENSATION AS A ROUTE TO HETEROCYCLES: SYNTHESIS OF 1,4-DIDEOXY-1,4-IMINO-D-ARABINITOL, FAGOMINE, 1-DEOXYNOJIRIMYCIN AND 1-DEOXYMANNOJIRIMYCIN
-
1,4-Dideoxy-1,4-imino-D-arabinitol, fagomine (1,2,5-trideoxy-1,5-imino-D-arabinohexitol), 1-deoxynojirimycin (1,5-dideoxy-1,5-imino-D-glucitol) and 1-deoxymannojirimycin (1,5-dideoxy-1,5-imino-D-mannitol) have been prepared via fructose-1,6-diphosphate aldolase catalyzed condensation followed by catalytic intramolecular reductive amination.
- Pederson, Richard L.,Wong, Chi-Huey
-
p. 477 - 480
(2007/10/02)
-
- Synthesis of Analogues of 1,3-Dihydroxyacetone Phosphate and Glyceraldehyde 3-Phosphate for Use in Studies of Fructose-1,6-diphosphate Aldolase
-
This paper describes the synthesis of five analogues of dihydroxyacetone phosphate (3-azidohydroxyacetone 1-phosphate (5), 3-(acetylamino)hydroxyacetone 1-phosphate (12), (R)-1,3-dihydroxy-2-butanone 1-phosphate (18), (+/-)-1,3-dihydroxy-2-butanone 3-phosphate (26), and phosphonomethyl glycolate (31)).The syntheses of 18 and 26 are based on a new reaction: that is, the introduction of the phosphate group by the reaction of a diazo ketone with dibenzyl phosphate.These methods provide easy access to a number of compounds that are potential substrates for the synthetically useful enzyme aldolase (fructose-1,6-diphosphate aldolase from rabbit muscle, EC 4.1.2.13, RAMA) and perhaps for other enzymes of glycolysis.This paper also describes syntheses of 14 aldehydes for examination as substrates for aldolase.When the precursor was available, ozonolysis of vinyl groups proved to be the best route to the corresponding aldehydes.
- Bischofberger, Norbert,Waldmann, Herbert,Saito, Tohru,Simon, Ethan S.,Lees, Watson,et al.
-
p. 3457 - 3465
(2007/10/02)
-