- Increasing Complexity: A Practical Synthetic Approach to Three-Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties
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A short synthetic approach with broad scope to access five- to seven-membered cyclic sulfoximines in only two to three steps from readily available thiophenols is reported. Thus, simple building blocks were converted to complex molecular structures by a s
- Boulard, Emilie,Ganzer, Ursula,Lücking, Ulrich,Lienau, Philip,Oertel, Luisa,Sch?fer, Martina,Zibulski, Vivien
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- Synthesis of α-Cyano and α-Sulfonyl Cyclic Ethers via Intramolecular Reactions of Peroxides with Sulfone- And Nitrile-Stabilized Carbanions
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The intramolecular reaction of carbon nucleophiles with oxygen-centered electrophiles has been little explored outside of nucleophilic epoxidation. We now report the synthesis of sulfonyl- and cyano-substituted oxacycles via intramolecular reaction of sul
- Horn, Alissa,Dussault, Patrick H.
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p. 14611 - 14626
(2019/11/13)
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- Pummerer Synthesis of Chromanes Reveals a Competition between Cyclization and Reductive Chlorination
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The competition between an unprecedented reductive chlorination and the Pummerer reaction was studied and applied to the synthesis of benzofused oxygen heterocycles including 3-aminochromanes and in the intramolecular chlorination of activated aromatic ri
- Acosta-Guzmán, Paola,Rodríguez-López, Alvaro,Gamba-Sánchez, Diego
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supporting information
p. 6903 - 6908
(2019/09/30)
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- NR2B SELECTIVE NMDA-RECEPTOR ANTAGONISTS FOR TREATMENT OF IMMUNE-MEDIATED INFLAMMATORY DISEASES
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The present invention provides novel means and methods for treatment auf immunemediated inflammatory diseases.
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-
Paragraph 160
(2017/03/21)
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- Scandium(III) Triflate-Catalyzed anti-Markovnikov Hydrothiolation of Functionalized Olefins
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Scandium(III) triflate promoted highly selective addition of thiols to functionalized olefins under mild conditions. The addition follows anti-Markovnikov regioselectivities, which are unusual for Lewis acids-catalyzed hydrothiolation. This reaction marks broad functional groups tolerance, which opens a beneficial synthetic route to functionalized and biologically active thio-compounds. This method is broadly applicable and offers a simple work-up in the green manner.
- Kuciski, Krzysztof,Pawluc, Piotr,Hreczycho, Grzegorz
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p. 3936 - 3942
(2016/01/25)
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- Gas-phase S-alkylation of benzenethiol with aliphatic alcohols, ethers, esters, alkyl halides and olefins over halide cluster catalysts of Groups 5 and 6 transition metals
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Benzenethiol was reacted with methanol under a hydrogen stream over [(Nb6Cl12)Cl2(H2O) 4]·6H2O supported on silica gel. Catalytic activity of the cluster commenced above 250 °C, yielding methyl phenyl sulfide. The selectivity was 98% at 400 °C. Molybdenum, tantalum and tungsten halide clusters with the same octahedral metal framework also catalyzed the reaction. Primary alcohols with shorter alkyl chains were effective reagents for the S-alkylation. Aliphatic ethers, dialkyl carbonates, orthoesters and alkyl halides were effective reagents for the S-alkylation. When 1-hexene was applied to the reaction, spontaneous and catalytic S-alkylation proceeded simultaneously above 200 °C, yielding n-hexyl phenyl sulfide. When alkyl acetates were subjected to this reaction, the niobium cluster afforded S-phenyl thioacetate, and the other clusters afforded alkyl phenyl sulfides selectively. A Br?nsted acid site attributable to a hydroxo ligand, which is formed on the cluster complex by thermal activation, is proposed as the active site of the catalysts.
- Nagashima, Sayoko,Kudo, Kentaro,Yamazaki, Hitomi,Kamiguchi, Satoshi,Chihara, Teiji
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- NR2B-SELECTIVE NMDA-RECEPTOR ANTAGONISTS
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The present invention relates to compounds according to general formula (I) and pharmaceutical compositions comprising compounds according to general formula (I).
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Page/Page column 46
(2010/11/05)
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- Diastereoselective synthesis of tetrahydrofurans from Aryl 3-chloropropylsulfoxides and aldehydes
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Carbanions of aryl 3-chloropropylsulfoxides react with nonenolizable aldehydes to give 2,3-disubstituted tetrahydrofurans. Deprotonation of the sulfoxides carried out in the presence of aldehydes results in the addition of the carbanions to the carbonyl group of the aldehydes, followed by 1,5-intramolecular substitution of the resulting aldol-type anion to produce the tetrahydrofuran ring. The 2-aryl and 3-arylsulfinyl substituents are always in trans relation, and the reaction proceeds with high diastereoselectivity also in respect to the chiral sulfur atom. The diastereoselectivity is attributed to the cyclic transition state of the aldol addition and increases when the aromatic ring of the sulfoxide contains electron-withdrawing substituents, whereas that of the aldehyde has electron-donating groups.
- Komsta, Zofia,Barbasiewicz, Michal,Makosza, Mieczyslaw
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supporting information; experimental part
p. 3251 - 3259
(2010/08/19)
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- Synthesis and QSAR studies on hypotensive 1-[3-(4-substituted phenylthio) propyl]-4-(substituted phenyl) piperazines
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A series of 1-[3-(4-substituted phenylthio) propyl]-4-(substituted phenyl) piperazines has been synthesized and evaluated for hypotensive activity. The QSAR studies indicate that resonance and hydrophobic parameters of the aryl substituents are important
- Saxena, Anil K.,Rao, Jyoti,Chakrabarty, Ruchika,Saxena, Mridula,Srimal
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p. 1708 - 1712
(2007/10/03)
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- Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT4 receptor agonists
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It is thought that selective 5-HT4 receptor agonists-such as 4-amino-5-chloro-2-methoxy-N-[1-(6-oxo-6-phenylhexyl)piperidin-4-ylmethyl] benzamide (2)-have the ability to enhance both upper and lower gastrointestinal motility without any significant adverse effects. Modification of 2 was performed. Variation of the piperidin-4-ylmethyl moiety of 2 led to a decrease in the binding affinity for the 5-HT4 receptor. Following conversion of the carbonyl group on the benzoyl part to a hydroxyl or sulfoxide group, the binding affinity for the 5-HT4 receptor was retained although the effect on defecation was reduced. Many of the 4-amino-5-chloro-2-methoxy-N- (piperidin-4-ylmethyl)benzamides that had a ether or sulfide moiety in the side-chain part at the 1-position of the piperidine exhibited high affinity for the 5-HT4 receptor. Among these, phenylthio 41c and benzylthio derivative 44 were selective 5-HT4 receptor agonists, and had a similar effect on defecation to compound 2.
- Sonda, Shuji,Kawahara, Toshio,Katayama, Kenichi,Sato, Noriko,Asano, Kiyoshi
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p. 3295 - 3308
(2007/10/03)
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- SUBSTITUTED ANILINIC PIPERIDINES AS MCH SELECTIVE ANTAGONISTS
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This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therepeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier.
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Page column 138; 139
(2010/02/06)
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- Synthesis and pharmacological properties of benzamide derivatives as selective serotonin 4 receptor agonists
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A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamides with a polar substituent group at the 1-position of the piperidine ring was synthesized and evaluated for its effect on gastrointestinal motility. The benzoyl, phenylsulfonyl, and benzylsulfonyl derivatives accelerated gastric emptying and increased the frequency of defecation. One of them, 4-amino-N-[1-[3-(benzylsulfonyl)propyl]piperidin-4-ylmethyl]-5-chloro-2- methoxybenzamide (13a, Y-36912), was a selective 5-HT4 receptor agonist offering potential as a novel prokinetic with reduced side effects derived from 5-HT3- and dopamine D2 receptor-binding affinity. In the oral route of administration, this compound enhanced gastric emptying and defecation in mice, and has a possibility as a prokinetic agent, which is effective on both the upper and the lower gastrointestinal tract.
- Sonda, Shuji,Katayama, Kenichi,Kawahara, Toshio,Sato, Noriko,Asano, Kiyoshi
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p. 2737 - 2747
(2007/10/03)
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- Functionalized organolithium compounds of DTBB-catalyzed sulfur-lithium exchange
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The successive reaction of β- or γ-hydroxy or amino phenyl thioethers (1,4) with butyllithium and an excess of lithium powder in the presence of a catalytic amount of DTBB in THF at - 78°C leads to the formation of the corresponding β- or γ-functionalized organolithium compounds 2 or 5, respectively, which by treatment with different electrophiles [D2O, t- BuCHO, PhCHO, Me2CO, (CH2)4CO, (CH2)5CO] at temperatures ranging between - 78°C and room temperature yields, after hydrolysis with water, the expected functionalized alcohols or amines 3 or 6, respectively, in a completely regioselective manner.
- Foubelo, Francisco,Gutiérrez, Ana,Yus, Miguel
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p. 503 - 514
(2007/10/03)
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- N-substituted imidazol derivative
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The present invention is to provide novel imidazole derivatives effectual as an antihyperlipemic agent and therapeutic and preventive drugs for arteriosclerosis, and to provide methods for manufacturing the said derivatives. More particularly, the present invention is directed to the compounds represented by the following general formula [I]; STR1 wherein R1 is hydrogen or lower alkyl, n is 0 or 1, X is N-r1 wherein r1 is hydrogen or lower alkyl, O, S, SO, SO2, CH2, CH(CH3), CONH or C(r2)=NO wherein r2 is hydrogen or lower alkyl, m is 0 or an integer of from 1 to 12, and A is methyl or a group represented by the following general formula; STR2 wherein Y is N-r3 wherein r3 is hydrogen or lower alkyl, N(r4)SO2 wherein r4 is hydrogen or lower alkyl, O, S, SO, SO2, CH2, CH(CH3), CONH or C(r5)=NO wherein r5 is hydrogen or lower alkyl, R2 is a halogen, a lower alkyl, a lower alkoxy, a cycloalkyl or COOr6 wherein r6 is hydrogen or a lower alkyl, and l is 0, 1, 2 or 3, however, m denotes an integer of from 6 to 9 when A is methyl, or m denotes 0 or an integer of from 1 to 6 when A is a group represented by the following general formula; STR3 and X and Y are each independently CH2 when m is 0, the pharmaceutically-acceptable salts thereof and methods for manufacturing the said compounds and the pharmaceutically-acceptable salts thereof.
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- BENZOIC ACID COMPOUNDS AND USE THEREOF AS MEDICAMENTS
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Benzoic acid compounds of the formula STR1 wherein each symbol is as defined in the specification, optical isomers thereof and pharmaceutically acceptable salts thereof; pharmaceutical composition comprising this compound and pharmaceutically acceptable additive; and serotonin 4 receptor agonists, gastrointestinal prokinetic agents and therapeutic agents for various gastrointestinal diseases, which comprise this compound as active ingredient. The compounds of the present invention have high and selective affinity for serotonin 4 receptor, and show agonistic effects thereon. Accordingly, they are useful medications for the prophylaxis and treatment of various gastrointestinal diseases, central nervous disorders, cardiac function disorders, urinary diseases, and the like, as well as useful anti-nociceptors for analgesic use which increase threshold of pain.
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- A novel synthesis of 1,2,3,4-tetrahydroquinolines via Pummerer-type reaction of N-aryl-N-[(phenylsulfinyl)propyl]formamide
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A synthesis of 1,2,3,4-tetrahydroquinolines (TQs) 13 with two and three methoxyl groups on the benzene ring, was achieved via intramolecular cyclization of N-aryl-N-[(phenylsulfinyl)propyl]formamides 7 utilizing the Pummerer reaction as a key step. The reaction was carried out by using trifluoroacetic anhydride (TFAA) (method A) or TFAA-BF3 · Et2O (method B). The cyclization to 4-PhSTQs 8 proceeded effectively when the reaction center at the benzene ring was electronically activated by a methoxyl group. In the reaction of sulfoxide 7e having two OMe groups in the ortho- and para- positions, a different cyclization reaction leading to 1,5-benzothiazepine derivative 9 was observed, indicating that the high nucleophilicity of the benzene ring caused the unexpected reaction prior to cyclization to 4-PhSTQs 8. This route starting from methoxyanilines provides an efficient and convenient method of TQ synthesis.
- Toda, Jun,Sakagami, Michiya,Sano, Takehiro
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p. 1269 - 1275
(2007/10/03)
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- BENZOIC ACID COMPOUNDS AND MEDICINAL USE THEREOF
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A benzoic acid compound of the formula wherein each symbol is as defined in the specification, an optical isomer thereof and a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising this compound and a pharmaceutically acceptable additive, a serotonin 4 receptor agonist comprising this compound as an active ingredient, a gastrointestinal prokinetic agent and a therapeutic agent for gastrointestinal diseases. The compound of the present invention shows selective and high affinity for serotonin 4 receptors, activates same, is useful as a pharmaceutical agent for the prophylaxis and treatment of gastrointestinal diseases (e.g., reflux esophagitis; gastroesophageal reflux such as that accompanying cystic fibrosis; Barrett syndrome; intestinal pseudoileus; acute or chronic gastritis; gastric or duodenal ulcer; Crohn's disease; non-ulcer dyspepsia; ulcerative colitis; postgastrectomy syndrome; postoperative digestive function failure; delayed gastric emptying caused by gastric neurosis, gastroptosis, diabetes, and the like; gastrointestinal disorders such as indigestion, meteorism, abdominal indefinite complaint, and the like; constipation such as atonic constipation, chronic constipation, and that caused by spinal cord injury, pelvic diaphragm failure and the like; and irritable bowel syndrome), central nervous disorders (e.g., schizophrenia, depression, anxiety, disturbance of memory and dementia), cardiac function disorders (e.g., cardiac failure and myocardial ischemia), urinary diseases (e.g., dysuria caused by urinary obstruction, ureterolith, prostatomegaly, spinal cord injury, pelvic diaphragm failure, etc.), and shows superior absorption.
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- α-Fluorination of methyl phenyl sulfoxide and related compounds by molecular fluorine: A novel method for the introduction of fluorine into sulfoxides bearing α-H atoms
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Direct formation of α-fluorosulfones from sulfoxides bearing α-H atoms merely by reaction with molecular fluorine (5% F2/N2) is reported, and a novel non-Pummerer-type mechanism is proposed for this α-fluorination reaction.
- Toyota, Akemi,Ono, Yoshinori,Chiba, Jun,Sugihara, Takumichi,Kaneko, Chikara
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p. 703 - 708
(2007/10/03)
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- 3-Lithiopropyl tert-Butyl Thioether: A New γ-Functionalised Organolithium Compound (d3-Reagent) in Synthetic Organic Chemistry
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The reaction of 3-bromo or 3-chloropropyl tert-butyl thioether (1a or 1'a) with and excess of lithium powder and a catalytic amount of naphthalene (2.5 mol percent) in THF at -78 deg C followed by treatment with an electrophile (H2O, D2O, Me2S2, CO2) at the same temperature leads, after hydrolysis, to the expected products 2.ALternatively the process can be carried out under Barbier-type reaction conditions tCHO, PhCHO, Me2CO, (CH2)4CO, (CH2)5CO, PhCOMe, c-C3H5COPh> and using DTBB as the arene catalyst at 0 deg C.De-tert-butylation of products 2 with mercury(II) acetate and sulfhydric acid yields different sulfurated derivatives depending on the structure of the starting thioether.
- Almena, Juan,Foubelo, Francisco,Yus, Miguel
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p. 11883 - 11890
(2007/10/02)
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- Hexitol derivatives having vasodilative activity
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Disclosed is a hexitol derivative represented by the formula (I): STR1 wherein Q represents a formula selected from the group consisting of STR2 wherein a represents NH, O or S; each of b, c and d independently represents CH or N; each of R1, R2, R3 and R4 independently represents hydrogen, lower alkyl, trifluoromethyl, aryl, lower alkanoyloxy, amino, lower alkylamino, lower alkanoylamino, lower alkanoyl, aroyl, halogen, nitro, (CH2)m OR 7, (CH2)m SR7, (CH2)m CO2 R7 where R7 represents hydrogen or lower alkyl and m represents an integer of 0 to 3; each of R5 and R6 independently represents hydrogen or lower alkyl; U represents >N-- or STR3 W represents a single bond, --O-- or --S--; X represents STR4 wherein each of Y1 and Y2 independently represents hydrogen, lower alkyl, hydroxyl, lower alkanoyloxy, nitrile or phenyl; or Y1 and Y2 are combined together to form oxygen; each of Y3 and Y4 independently represents hydrogen or lower alkyl; and l is an integer of 0 to 6, and where l is an integer of 2 to 6, each STR5 may be the same or different; Z represents hydrogen or nitro; and, n is 2 or 3 or a pharmaceutically acceptable salt thereof. The compounds show prominent coronary vasodilative activities, and are useful in treating angina pectoris and myocardial infarction.
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- New Antihistaminic Theophylline or Theobromine Derivatives
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A series of 3,4-dihydro-1,3-dimethyl-7--1H-purine-2,6-diones and 3,7-dihydro-3,7-dimethyl-1--1H-purine-2,6-diones was synthesized and evaluated for antihistaminic activity.Some of them displayed good inhibition of both histamine-induced bronchospasm in the anesthetized guinea pig at 10 μ/kg by the intravenous route and of passive cutaneous anaphylaxis in the rat at 10 mg/kg by the oral route.Comparison of the two most active compounds revealed a higher antihistaminic activity with the compounds containing a (phenylthio)propyl group (1 and 2) as compared with that containing a phenoxy group.Compound 2 piperazin-1-yl>-2-hydroxypropyl>-1H-purine-2,6-dione> was selected for clinical trials on the basis of a comparative pharmacological study with chloropheniramine, ketotifen, promethazine, and theophylline.
- Pascal, Jean-Claude,Beranger, Serge,Pinhas, Henri,Poizot, Alain,Desiles, Jean-Pierre
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p. 647 - 652
(2007/10/02)
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- CARBON-SULFUR BOND CLEAVAGE BY BENZYNE GENERATED FROM 2-CARBOXYBENZENEDIAZONIUM CHLORIDE
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The reaction of cyclic sulfides with benzyne generated from 2-carboxybenzenediazonium chloride affords ω-chloroalkyl phenyl sulfides in good yields.A similar type of reaction was also observed with acyclic sulfides.
- Nakayama, Juzo,Hoshino, Keiichi,Hoshino, Masamatsu
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p. 677 - 678
(2007/10/02)
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- THE COMPATIBILITY OF THE CYANO AND ALKYL CHLORIDE FUNCTIONS IN PHENYLTHIOALKYLATION REACTIONS OF O-SILYLATED ENOLATES
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The compatibility of the cyano group and of chlorides with the conditions of phenylthioalkylation of O-silylated enolates has been demonstrated.
- Lee, Thomas V.,Visani, Naina
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p. 5559 - 5560
(2007/10/02)
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- Piperazine derivatives of theophylline
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New compounds of the formula STR1 and the pharmaceutically acceptable acid addition salts thereof, wherein Z1 and Z2 are each independently selected from the group consisting of CH2, CHOB and C=O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z1 is CHOB; m is an integer from 0-4 but cannot be zero when Z2 is CHOB; and R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; are antihistamines and are therefore useful in the treatment of respiratory diseases including asthma, hay fever, allergies and the common cold.
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- Piperazine derivatives of theophylline
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New compounds of the formula STR1 and the pharmaceutically acceptable acid addition salts thereof, wherein M is selected from the group consisting of hydrogen, morpholino, benzylamino, di-n-lower alkylamine, n-lower alkylamine, and aryl piperazino; Z1 and Z2 are each independently selected from the group consisting of CH2, CHOB and C=O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z1 is CHOB; m is an integer from 0-4 but cannot be zero when Z2 is CHOB, or when m is hydrogen; R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; and R4 and R5 are each independently lower alkyl, with the proviso that both R4 and R5 cannot be methyl when M is hydrogen; are antihistamines and are therefore useful in the treatment of respiratory diseases including asthma, hay fever, allergies and the common cold. They are also vasodilators.
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- Piperazine alkanols
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This invention relates to variously substituted piperazine derivatives. S compounds possess therapeutically useful vasodilator properties.
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