- Regioselectivity in Forming Dipole-Stabilized Anions. Sites of Metalation of Indolines, Tetrahydroquinolines, and Benzazepines Activated by N-Formimidoyl or N-Boc Groups
-
Metalation of the title compounds indicated that the formamidine-equipped indolines or 1,2,3,4-tetrahydroquinolines give rise solely to C-2 alkylation products (5,6) whereas the corresponding N-t-Boc systems give only ortho aryl alkylation (7,8).
- Meyers, A. I.,Milot, Guy
-
-
Read Online
- Dehydrogenative and Redox-Neutral N-Heterocyclization of Aminoalcohols Catalyzed by Manganese Pincer Complexes
-
A new manganese catalyzed heterocyclization of aminoalcohols has been accomplished. A wide range of heterocycles were synthesized, including 1,2,3,4-tetrahydroquinolines, dihydroquinolinones, and 2,3,4,5-tetrahydro-1H-benzo[b]azepines. The reaction is performed under mild reaction conditions using air and moisture stable manganese catalysts. The desired heterocycles were obtained in good to excellent yields.
- Brzozowska, Aleksandra,Rueping, Magnus,Sklyaruk, Jan,Zubar, Viktoriia
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supporting information
(2022/03/17)
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- Tetrahydroquinoline-Capped Histone Deacetylase 6 Inhibitor SW-101 Ameliorates Pathological Phenotypes in a Charcot-Marie-Tooth Type 2A Mouse Model
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Histone deacetylase 6 (HDAC6) is a promising therapeutic target for the treatment of neurodegenerative disorders. SW-100 (1a), a phenylhydroxamate-based HDAC6 inhibitor (HDAC6i) bearing a tetrahydroquinoline (THQ) capping group, is a highly potent and sel
- Shen, Sida,Picci, Cristina,Ustinova, Kseniya,Benoy, Veronick,Kutil, Zsófia,Zhang, Guiping,Tavares, Maurício T.,Pavlí?ek, Ji?í,Zimprich, Chad A.,Robers, Matthew B.,Van Den Bosch, Ludo,Ba?inka, Cyril,Langley, Brett,Kozikowski, Alan P.
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p. 4810 - 4840
(2021/05/07)
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- Indirect reduction of CO2and recycling of polymers by manganese-catalyzed transfer hydrogenation of amides, carbamates, urea derivatives, and polyurethanes
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The reduction of polar bonds, in particular carbonyl groups, is of fundamental importance in organic chemistry and biology. Herein, we report a manganese pincer complex as a versatile catalyst for the transfer hydrogenation of amides, carbamates, urea derivatives, and even polyurethanes leading to the corresponding alcohols, amines, and methanol as products. Since these compound classes can be prepared using CO2as a C1 building block the reported reaction represents an approach to the indirect reduction of CO2. Notably, these are the first examples on the reduction of carbamates and urea derivatives as well as on the C-N bond cleavage in amides by transfer hydrogenation. The general applicability of this methodology is highlighted by the successful reduction of 12 urea derivatives, 26 carbamates and 11 amides. The corresponding amines, alcohols and methanol were obtained in good to excellent yields up to 97%. Furthermore, polyurethanes were successfully converted which represents a viable strategy towards a circular economy. Based on control experiments and the observed intermediates a feasible mechanism is proposed.
- Liu, Xin,Werner, Thomas
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p. 10590 - 10597
(2021/08/20)
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- Reaction of Vinyl Aziridines with Arynes: Synthesis of Benzazepines and Branched Allyl Fluorides
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We report the cycloaddition between vinyl aziridines and arynes. Depending on the reaction conditions and the choice of the aryne precursor, the aziridinium intermediate can be trapped through two distinct mechanistic pathways. The first one proceeds through a formal [5+2] cycloaddition to furnish valuable multi-substituted benzazepines. In the second pathway, the aziridinium is intercepted by a fluoride ion to afford allylic fluorides in good yields. Both reactions proceed stereospecifically and furnish enantiopure benzazepines and allylic fluorides.
- Kaldas, Sherif J.,Kran, Eva,Mück-Lichtenfeld, Christian,Yudin, Andrei K.,Studer, Armido
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p. 1501 - 1505
(2020/02/05)
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- Mild, Metal-Free Oxidative Ring-Expansion Approach for the Synthesis of Benzo[ b]azepines
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Benzo[b]azepines are important structural motifs for the pharmaceutical industry. However, their syntheses are usually lengthy, involving several steps, transition-metal catalysts, and/or harsh conditions. A novel, general, mild, and metal-free oxidative ring expansion tandem reaction of hydroquinolines with TMSCHN2 as a versatile soft nucleophile to gain access to these valuable compounds in a simple and straightforward manner is presented.
- Stockerl, Sebastian,Danelzik, Tobias,Piekarski, Dariusz G.,García Manche?o, Olga
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p. 4535 - 4539
(2019/06/17)
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- Formal Deoxygenative Hydrogenation of Lactams Using PNHP-Pincer Ruthenium Complexes under Nonacidic Conditions
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A formal deoxygenative hydrogenation of amides to amines with RuCl2(NHC)(PNHP) (NHC = 1,3-dimethylimizadol-2-ylidene, PNHP = bis(2-diphenylphosphinoethyl)amine) is described. Various secondary amides, especially NH-lactams, are reduced with H2 (3.0-5.0 MPa) to amines at a temperature range of 120-150 °C with 1.0-2.0 mol % of PNHP-Ru catalysts in the presence of Cs2CO3. This process consists of (1) deaminative hydrogenation of secondary amides to generate primary amines and alcohols, (2) dehydrogenative coupling of the transient amines with alcohols to generate imines, and (3) hydrogenation of imines to give the formally deoxygenated secondary amine products.
- Ogata, Osamu,Nara, Hideki,Matsumura, Kazuhiko,Kayaki, Yoshihito
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supporting information
p. 9954 - 9959
(2019/12/24)
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- Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines
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The first transition-metal-free catalytic protocol for controlled reduction of amide functions using cheap and bench-stable hydrosilanes as reducing agents has been established. By altering the hydrosilane and solvent, the new method enables the selective cleavage of unactivated C-O bonds in amides and allows the C-N bonds to selectively break via the deacylated cleavage. Overall, this novel process may offer a versatile alternative to current methodologies employing stoichiometric metal systems for the controlled reduction of carboxamides.
- Yao, Wubing,He, Lili,Han, Deman,Zhong, Aiguo
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- Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines
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The first transition-metal-free catalytic protocol for controlled reduction of amide functions using cheap and bench-stable hydrosilanes as reducing agents has been established. By altering the hydrosilane and solvent, the new method enables the selective cleavage of unactivated C-O bonds in amides and allows the C-N bonds to selectively break via the deacylated cleavage. Overall, this novel process may offer a versatile alternative to current methodologies employing stoichiometric metal systems for the controlled reduction of carboxamides.
- Yao, Wubing,He, Lili,Han, Deman,Zhong, Aiguo
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p. 14627 - 14635
(2019/12/02)
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- 4 - Substituted benzene sulfonamide derivative and its preparation method and application
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The present invention discloses a class of new 4-substituted benzene sulfonamide derivatives represented by a formula (I), wherein the 4-substituted benzene sulfonamide derivatives have good antitumor activity, and each group is defined in the specification. The present invention further discloses a preparation method of the derivative, a pharmaceutical composition containing the derivative, and applications of the 4-substituted benzene sulfonamide derivative and the pharmaceutical composition containing the derivative as the antitumor drug. The formula I is defined in the specification.
- -
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Paragraph 0139; 0159-0162
(2018/04/21)
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- LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism
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Oxytocin (OT) and its receptor (OT-R) are implicated in the etiology of autism spectrum disorders (ASD), and OT-R is a potential target for therapeutic intervention. Very few nonpeptide oxytocin agonists have currently been reported. Their molecular and in vivo pharmacology remain to be clarified, and none of them has been shown to be efficient in improving social interaction in animal models relevant to ASD. In an attempt to rationalize the design of centrally active nonpeptide full agonists, we studied in a systematic way the structural determinants of the affinity and efficacy of representative ligands of the V1a and V2 vasopressin receptor subtypes (V1a-R and V2-R) and of the oxytocin receptor. Our results confirm the subtlety of the structure-affinity and structure-efficacy relationships around vasopressin/oxytocin receptor ligands and lead however to the first nonpeptide OT receptor agonist active in a mouse model of ASD after peripheral ip administration.
- Frantz, Marie-Céline,Pellissier, Lucie P.,Pflimlin, Elsa,Loison, Stéphanie,Gandiá, Jorge,Marsol, Claire,Durroux, Thierry,Mouillac, Bernard,Becker, Jér?me A. J.,Le Merrer, Julie,Valencia, Christel,Villa, Pascal,Bonnet, Dominique,Hibert, Marcel
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p. 8670 - 8692
(2018/10/05)
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- Novel nonmetal catalytic bidirectional selective reduction method of tertiary aromatic amide
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The invention relates to a novel effective bidirectional selective environment-friendly method for hydrosilation reduction of tertiary aromatic amide and an organic silicon reagent. The method comprises the following steps: selecting a nonmetal catalytic system, and selectively preparing a secondary or tertiary organic amine compound by successively catalyzing tertiary aromatic amide and cheap PHMS or triethoxysilane under a mild condition. By adopting the method, the bidirectional selective reduction of the tertiary aromatic amide is realized by innovatively utilizing an electronic effect and steric hindrance difference of an organic silicon reagent at first time, so that a brand new strategy is provided for the reduction of amide and derivative of the amide, the defects of the traditional method that the substrate functional group is poor in compatibility, the production cost is high and the like can be overcome, and the application prospect of the amine compound prepared in industrial production or laboratory is promising.
- -
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Paragraph 0098; 0099; 0100; 0101
(2017/10/22)
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- Synthesis, anti-cancer evaluation of benzenesulfonamide derivatives as potent tubulin-targeting agents
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A series of benzenesulfonamide derivatives were synthesized and evaluated for their anti-proliferative activity and interaction with tubulin. These new derivatives showed significant activities against cellular proliferative and tubulin polymerization. Compound BA-3b proved to be the most potent compound with IC50value ranging from 0.007 to 0.036 μM against seven cancer cell lines, and three drug-resistant cancer cell lines, which indicated a promising anti-cancer agent. The target tubulin was also verified by dynamic tubulin polymerization assay and tubulin intensity assay.
- Yang, Jun,Yang, Simin,Zhou, Shanshan,Lu, Dongbo,Ji, Liyan,Li, Zhongjun,Yu, Siwang,Meng, Xiangbao
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p. 488 - 496
(2016/07/19)
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- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
- -
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Paragraph 0658
(2015/09/22)
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- Amino-alcohol cyclization: Selective synthesis of lactams and cyclic amines from amino-alcohols
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By employing an amination catalyst, previously used in the direct synthesis of amines from alcohol with ammonia, n-amino-alcohols could be selectively cyclized to either the amide or the amine. By the addition of water, the amine could be produced as the major product whereas adding a sacrificial ketone as a hydrogen acceptor resulted in the amide as the major product. Without an additive a mixture of both the amine and the amide was observed. N-substituted amino-alcohols solely gave cyclic amines under these conditions. From 2-(n-alkanol) anilines the cyclic amines were produced, where the n-propanol derivative selectively formed quinoline as the major product.
- Pingen, Dennis,Vogt, Dieter
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- Discovery of a tetracyclic quinoxaline derivative as a potent and orally active multifunctional drug candidate for the treatment of neuropsychiatric and neurological disorders
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We report the synthesis and structure-activity relationships of a class of tetracyclic butyrophenones that exhibit potent binding affinities to serotonin 5-HT2A and dopamine D2 receptors. This work has led to the discovery of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H- pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl) -1-(4-fluorophenyl)-butan-1-one 4-methylbenzenesulfonate (ITI-007), which is a potent 5-HT2A antagonist, postsynaptic D2 antagonist, and inhibitor of serotonin transporter. This multifunctional drug candidate is orally bioavailable and exhibits good antipsychotic efficacy in vivo. Currently, this investigational new drug is under clinical development for the treatment of neuropsychiatric and neurological disorders.
- Li, Peng,Zhang, Qiang,Robichaud, Albert J.,Lee, Taekyu,Tomesch, John,Yao, Wei,Beard, J. David,Snyder, Gretchen L.,Zhu, Hongwen,Peng, Youyi,Hendrick, Joseph P.,Vanover, Kimberly E.,Davis, Robert E.,Mates, Sharon,Wennogle, Lawrence P.
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p. 2670 - 2682
(2014/04/17)
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- Enantiocontrolled total synthesis of (-)-mersicarpine
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A racemic synthesis of mersicarpine (1) was achieved by the Mizoroki-Heck reaction and a DIBALH-mediated reductive ring-expansion reaction. Based on a first-generation synthesis, a second-generation enantiocontrolled total synthesis of (-)-mersicarpine (1) was achieved by an 8-pot/11-step sequence in 21 % overall yield from commercially available 2-ethylcyclohexanone. Subjection of a ketoester, which was prepared by an asymmetric Michael addition (according to the protocol by d'Angelo and Desmaele), and phenylhydrazine to modified Fischer indole conditions provided a six-membered tricyclic indole. Benzylic oxidation and subsequent oxime formation provided a ketoxime, which was treated with diisobutylaluminum hydride (DIBALH) to construct the characteristic azepinoindole skeleton in good yield. In the DIBALH-mediated reductive ring-expansion reaction, gradually increasing the reaction temperature and in situ-protection of the nitrogen in an oxygen-sensitive azepinoindole with a benzyloxycarbonyl (Cbz) group were crucial for the high-yielding process. With these methodologies, the short-step and efficient synthesis of (-)-mersicarpine was accomplished. Several synthetic efforts are also described. Copyright
- Iwama, Yusuke,Okano, Kentaro,Sugimoto, Kenji,Tokuyama, Hidetoshi
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p. 9325 - 9334
(2013/07/26)
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- Ring-expansion reaction of oximes with aluminum reductants
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The ring-expansion reactions of heterocyclic ketoximes and carbocyclic ketoximes with several reductants such as AlHCl2, AlH3 (alane), LiAlH4, LiAlH(OtBu)3, and (MeOCH 2CH2O)2AlH2Na (Red-Al) were examined. Among reductants, AlHCl2 (LiAlH4:AlCl 3 = 1:3) in cyclopentyl methyl ether (CPME) has been found to be a suitable reagent for the reaction, and the rearranged cyclic secondary amines were obtained in good to excellent yields.
- Cho, Hidetsura,Iwama, Yusuke,Mitsuhashi, Nakako,Sugimoto, Kenji,Okano, Kentaro,Tokuyama, Hidetoshi
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scheme or table
p. 7348 - 7355
(2012/09/07)
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- A Lewis acid mediated schmidt reaction of benzylic azide: Synthesis of sterically crowded aromatic tertiary amines
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An efficient one-pot synthesis of sterically hindered aromatic tertiary amines through Lewis acid induced intermolecular Schmidt reaction of benzylic azides is described. In the presence of EtAlCl2, benzylic azide underwent a smooth Schmidt reaction to give the corresponding iminium ion, which, upon reduction with NaBH4 in situ, afforded the tertiary amine. The effects of substituents on the aromatic ring and the steric effects of the alkyl side chain have also been studied.
- Murali, Annamalai,Puppala, Manohar,Varghese, Babu,Baskaran, Sundarababu
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supporting information; experimental part
p. 5297 - 5302
(2011/11/12)
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- Regiospecific rearrangement of hydroxylamines to secondary amines using diisobutylaluminum hydride
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A systematic investigation of a reductive ring-expansion reaction of N-monosubstituted hydroxylamines with diisobutylaluminum hydride (DIBALH) was carried out. The reaction regiospecifically provided a variety of bicyclic or tricyclic heterocycles or linear secondary amines containing nitrogen attached to an aromatic ring. The Japan Institute of Heterocyclic Chemistry.
- Cho, Hidetsura,Sugimoto, Kenji,Iwama, Yusuke,Mitsuhashi, Nakako,Okano, Kentaro,Tokuyama, Hidetoshi
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experimental part
p. 1633 - 1644
(2011/05/05)
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- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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- Ionic diamine rhodium complex catalyzed hydroaminomethylation of 2-allylanilines
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Ionic diamine rhodium complexes catalyze the hydroaminomethylation of 2-allylanilines. The reaction involves initial hydroformylation followed by reductive amination, which provides direct access to 1,2,3,4- tetrahydroquinolines and 2,3,4,5-1H-1-benzazepi
- Okuro, Kazumi,Alper, Howard
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scheme or table
p. 4959 - 4961
(2011/01/12)
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- Regioselective synthesis of heterocycles containing nitrogen neighboring an aromatic ring by reductive ring expansion using diisobutylaluminum hydride and studies on the reaction mechanism
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(Chemical Equation Presented) A systematic investigation of the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic ringswith diisobutylaluminum hydride (DIBALH) is described. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring, including indoline, 1,2,3,4,5,6-hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b] [1,4]oxazine, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6- hexahydroazepino[3,2-b]-indole, 2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H-benzothieno[3,2-b]-azepine, 5,6-dihydrophenanthridine, and 5,6,11,12-tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the rearrangement was investigated on the basis of the restricted Becke three-parameter plus Lee-Yang-Parr (B3LYP) density functional theory (DFT) with the 6-31G (d) basis set. It was found that the reaction proceeds through a three-centered transition state via a stepwise mechanism because the potential energy curve along the intrinsic reaction coordinate (IRC) had twomaxima (saddle points; TS1 and TS2) and the partial phenonium cation intermediate C. In addition to cyclic ketoximes fused to aromatic rings, the reactions of various cyclic and acyclic ketoximeswere examined to investigate preference of migrating group. It was found that themore electron-rich group migrated preferentially to give the corresponding secondary amines.
- Cho, Hidetsura,Iwama, Yusuke,Sugimoto, Kenji,Mori, Seiji,Tokuyama, Hidetoshi
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scheme or table
p. 627 - 636
(2010/04/29)
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- COMPOUND HAVING 11 ?-HSD1 INHIBITORY ACTIVITY
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The present invention provides compounds having excellent 11β-HSD1 inhibitory activity. A compound represented by the following formula (I): [wherein X1 represents an oxygen atom, or the formula -(CR11R12)p-, etc., Y1 represents a hydrogen atom, a hydroxyl group, etc., Z1 represents an oxygen atom or the formula -(NR14)-, R1 represents a hydrogen atom, a halogen atom, a cyano group, a C1-4 alkyl group, a C1-4 alkyl group substituted with 1 to 3 halogen atoms, a C1-4 alkoxy group, a C1-4 alkoxycarbonyl group, a carboxyl group, a carbamoyl group, or an amino group, and m represents an integer of 1 or 2, and R2 represents a hydrogen atom or a C1-4 alkyl group, and n represents an integer of 1 or 2].
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Page/Page column 12
(2010/04/25)
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- Regiospecific synthesis of unsubstituted basic skeletons of heterocycles containing nitrogen neighboring an aromatic ring by the reductive ring expansion reaction using diisobutylaluminum hydride
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A systematic investigation of reductive ring expansion reaction of oximes with diisobutylaluminum hydride (DIBAH) was performed. The reaction regiospecifically provided a variety of unsubstituted bicyclic heterocycles 3a-3g or tricyclic heterocycles 3h, 3j-3l that contained nitrogen attached to an aromatic ring.
- Cho, Hidetsura,Iwama, Yusuke,Sugimoto, Kenji,Kwon, Eunsang,Tokuyama, Hidetoshi
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experimental part
p. 1183 - 1190
(2009/11/30)
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- QUINOLONE AND TETRAHYDROQUINOLONE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
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The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.
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Page/Page column 72
(2008/12/08)
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- Pharmaceutical Compositions Comprising Nitrogen-Containing Fused Ring Coumpounds
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[Problems] The present invention provides pharmaceutical composition which is effective for the prophylaxis or treatment of pathology showing involvement of uric acid (hyperuricemia, gouty tophus, acute gout arthritis, chronic gout arthritis, gouty kidney, urolithiasis, renal function disorder, coronary arterial disease, ischemic heart disease and the like) and the like, and is superior in the time-course stability and dissolution property (disintegration property). [Solving Means] The pharmaceutical composition of the present invention is a pharmaceutical composition comprising a nitrogen-containing fused ring compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable additives, wherein the nitrogen-containing fused ring compound or a pharmaceutically acceptable salt thereof is not in contact with a basic additive: wherein each symbol is as described in the specification.
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- Production Method of Nitrogen-Containing Fused Ring Compounds
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[Problems] The present invention provides a superior production method and a superior purification method of compounds effective for the treatment or prophylaxis of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like. [Means] A compound represented by the following formula [2] or a pharmaceutically acceptable salt thereof can be produced by reacting a compound represented by the following formula [3] or a salt thereof with a compound represented by the following formula [4], a salt thereof or a reactive derivative thereof. Moreover, crystallization of a compound represented by the formula [2] can be performed with industrially superior workability, and high quality crystals of a compound represented by the formula [2] can be obtained. wherein each symbol is as defined in the description.
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Page/Page column 52
(2010/11/30)
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- LXR modulators
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A compound of formula I wherein A, X, q, R1, R2a, R2b, R2c, R3a, and R3b are defined herein.
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Page/Page column 47
(2010/11/26)
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- Nitrogen-containing fused ring compounds and use thereof
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A URAT1 activity inhibitor containing a nitrogen-containing fused ring compound represented by the following formula [1]: wherein each symbol is as defined in the description. The present invention is useful for the prophylaxis or treatment of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like.
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Page/Page column 88-89
(2010/11/25)
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- Synthesis of tetrahydrobenzazepinesulfonamides and their rearrangement to diarylsulfones
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A new class of diarylsulfones, in which tetrahydrobenzazepine comprises one of the aromatic moieties, has been synthesized via the acid-catalyzed rearrangement of several substituted benzazepinesulfonamides. The rearrangement is normally ortho but in at l
- Ren, Hui,Zanger, Murray,McKee, James R.
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p. 355 - 363
(2007/10/03)
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- Compounds
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The present invention provides a compound of formula I comprising: a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof.
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Page/Page column 15
(2010/02/15)
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- COMPOUNDS FOR MODULATING TRPV3 FUNCTION
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The present application relates to compounds and methods for treating pain and other conditions related to TRPV3.
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Page/Page column 125
(2008/06/13)
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- Facile rearrangement of O-silylated oximes on reduction with boron trifluoride/borane
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Aromatic O-triisopropylsilyl ketoximes were efficiently rearranged to cyclic and acyclic aniline derivatives on reduction with BF3- ethearate /borane. The bulk of the substituents on the silicon atom, the size of the aliphatic ring, and the presence of alkoxy substituents on the aryl group all play an important role in the aniline.
- Ortiz-Marciales, Margarita,Rivera, Luis D.,De Jesus, Melvin,Espinosa, Sandraliz,Benjamin, Josue A.,Casanova, Orlando E.,Figueroa, Irving G.,Rodriguez, Sheila,Correa, Wilbert
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p. 10132 - 10134
(2007/10/03)
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- Substituted heterocycle fused gamma-carbolines
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The present invention is directed to methods of treating addictive behavior and sleep disorders by administering compounds represented by structural Formula (I) or pharmaceutically acceptable salt forms thereof, wherein R1, R5, R6a, R6b, R7, R8, R9, X, b, k, m, and n, and the dashed lines are described herein. The compounds used in the method of treatment of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including addictive behavior and sleep disorders.
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- Novel synthetic strategy of N-arylated heterocycles via sequential palladium-catalyzed intra- and inter-arylamination reactions
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The use of an in situ generated Pd(0) catalyst associated to N,N′-bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene (SIPr) as a ligand and t-BuONa as the base for sequential intra- followed by intermolecular aryl animation is described. The method has been applied to the synthesis of N-arylated five-, six- and seven-membered nitrogen heterocycles.
- Omar-Amrani, Rafik,Schneider, Raphael,Fort, Yves
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p. 2527 - 2534
(2007/10/03)
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- Piperadinyl-substituted pyridylalkane, alkene and alkine carboxamides
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The invention relates to new piperidinyl-substituted pyridyl carboxamides of the general formula (I), wherein the structure element E has meanings (E1) or (E2) and whereby the heterocyclic ring can optionally have a double bond. These substances have especially high cytostatic activities and pronounced immunosuppressive properties which make them suitable for therapeutic treatment in broad tumor spectrum.
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- Substituted heterocycle fused gamma-carbolines
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The present invention is directed to certain novel compounds represented by structural Formula (I) or pharmaceutically acceptable salt forms thereof, wherein R1, R5, R6a, R6b, R7, R8, R9, X, b, k, m, and n, and the dashed lines are described herein. The invention is also concerned with pharmaceutical formulations comprising these novel compounds as active ingredients and the use of the novel compounds and their formulations in the treatment of certain disorders. The compounds of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including obesity, anxiety, depression, psychosis, schizophrenia, sleep disorders, sexual disorders, migraine, conditions associated with cephalic pain, social phobias, and gastrointestinal disorders such as dysfunction of the gastrointestinal tract motility.
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- PURINE DERIVATIVES AS KINASE INHIBITORS
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The present invention provides kinase inhibitors of Formula I.
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Page/Page column 32-33
(2008/06/13)
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- Synthesis and biological evaluation of benzazepine oxazolidinone antibacterials
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Novel benzazepine oxazolidinone antibacterials were synthesized and evaluated against clinically relevant susceptible and resistant organisms. The effect of ring nitrogen position and N-substitution on antibacterial activity is examined.
- Johnson, Paul D.,Aristoff, Paul A.,Zurenko, Gary E.,Schaadt, Ronda D.,Yagi, Betty H.,Ford, Charles W.,Hamel, Judith C.,Stapert, Douglas,Moerman, Judy K.
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p. 4197 - 4200
(2007/10/03)
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- Efficient nickel-mediated intramolecular amination of aryl chlorides
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(Matrix presented) The use of an in situ generated Ni(0) catalyst associated with 2,2′-bipyridine or N,N′ -bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene (SIPr) as a ligand and NaO-t-Bu as the base for the intramolecular coupling of aryl chlorides with amines is described. The procedure has been applied to the formation of five-, six-, and seven-membered rings.
- Omar-Amrani, Rafik,Thomas, Antoine,Brenner, Eric,Schneider, Raphael,Fort, Yves
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p. 2311 - 2314
(2007/10/03)
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- Oxidative cyclization of amino alcohols catalyzed by a Cp*lr complex. Synthesis of indoles, 1,2,3,4-tetrahydroquinolines, and 2,3,4,5-tetrahydro-1-benzazepine
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A new iridium-catalyzed oxidative cyclization of amino alcohols has been revealed. Indole derivatives are synthesized in good to excellent yields from 2-aminophenethyl alcohols by means of a [Cp*IrCl2]2/K2CO3 catalytic system. The present catalytic system is also effective for syntheses of 1,2,3,4-tetrahydroquinolines from 3-(2-aminophenyl)propanols and 2,3,4,5-tetrahydro-1-benzazepine from 4-(2-aminophenyl)butanol.
- Fujita, Ken-Ichi,Yamamoto, Kazunari,Yamaguchi, Ryohei
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p. 2691 - 2694
(2007/10/03)
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- 4-heterocyclyl-substituted quinazoline derivatives, processes for their preparation and their use as anti-cancer agents
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This invention relates to certain 4-aminoquinazolines and the pharmaceutically acceptable salts and stereoisomers thereof, the formula whereof are described herein. The compounds are useful for the treatment of hyperproliferative diseases, particularly as anti-cancer agents.
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- Effect of ring size or an additional heteroatom on the potency and selectivity of bicyclic benzylamine-type inhibitors of phenylethanolamine N- methyltransferase
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In the search for potent and selective inhibitors of the enzyme phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28), we examined the effect of ring size or an additional heteroatom in the conformationally- restricted benzylamine-type PNMT inhibitors. Based on semiempirical calculations (MNDO) and molecular modeling studies, PNMT-inhibitory activity of these compounds seemed to be dependent on (a) the torsion angle between the plane of the aromatic ring and the endo N atom lone pair (τ2 angle), with the optimal value of τ2 being about -75°, and (b) the amount of steric bulk about the 3-position of 1,2,3,4-tetrahydroisoquinoline (5, THIQ). 2,3,4,5-Tetrahydro-1H-2-benzazepine (6) was found to have the highest selectivity (PNMT K(i) = 3.34 μM, α2 K(i) = 11 μM, selectivity = 3.2) as compared to other homologues of THIQ (PNMT K(i) = 9.67 μM, α2 K(i) = 0.35 μM, selectivity = 0.036). The higher PNMT-inhibitory activity of 6 was attributed to favorable steric interactions of the puckered methylene groups in the putative bioactive conformation of 6 at the PNMT active site, whereas unfavorable interactions of these puckered methylene groups at the α2- adrenoceptor were thought to be the cause of reduced α2 affinity of 6. No further enhancement of the selectivity of the benzazepine ring system could be obtained via introduction of a second heteroatom (N, O, S) at the 5- position in this ring system.
- Grunewald, Gary L.,Dahanukar, Vilas H.,Ching, Piao,Criscione, Kevin R.
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p. 3539 - 3546
(2007/10/03)
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- Microbiological Transformations, Part 6. Microbiological Transformations of Acyl Derivatives of Indoline, 1,2,3,4-Tetrahydroquinoline, 1,2,3,4-Tetrahydroisoquinoline and 2,3,4,5-Tetrahydro-1H-1-benzazepine with the Fungus Cunninghamella elegans
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Incubation of N-benzoyl and N-(p-toluoyl)indoline with Cunninghamella elegans resulted in reductive cleavage with the formation of indoline and the corresponding benzyl alcohol.N-Acetylindoline underwent normal benzylic hydroxylation ond open chain analogues of N-(p-toluoyl)indolines were hydroxylated at the aryl methyl group by C. elegans.The fungus effected benzylic oxidation at the 4-position on N-benzoyl-1,2,3-tetrahydroquinoline and in N-benzoyl-1,2,3,4-tetrahydroisoquinoline derivatives.N-(p-Toluoyl)-1,2,3,4-tetrahydroquinoline and N-(p-ethylbenzoyl)-1,2,3,4-tetrahydroisoquinoline were, however, hydroxylated at the alternative 4'-benzylic position.Incubation of N-(p-toluoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine with C. elegans gave 5-hydroxy-N-(p-toluoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine
- Crabb, Trevor,Soilleux, Stephanie L.
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p. 1381 - 1386
(2007/10/02)
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- Photoreactions of α-Amino Ketones Derived from Heterocyclic Secondary Amines
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The photochemical behaviour of N-phenacyl nitrogen heterocycles varies with the size of the heterocyclic ring.U.v. irradiation of 1-phenacylindoline and 2,3,3-trimethyl-1-phenacylindoline resulted in type-II fission to give acetophenone and indole or 2,3,3-trimethyl-3H-indole, respectively.Indole was also produced, along with 2,3-diphenylbutane-2,3-diol, when indoline was irradiated with acetophenone.Both 1-phenacyl- and 1-(2-oxocyclohexyl)-1,2,3,4-tetrahydroquinoline underwent type-II cyclisation to azetidinol derivatives; fission was a minor process.In contrast, on irradiation of 5,6-dihydro-5- phenacylphenanthridine, type-II fission occurred to give acetophenone and phenanthridine.Irradiation of 2,3,4,5-tetrahydro-1-phenacyl-1H-benzazepine resulted in direct homolysis of the N-CH2CO bond to yield 2,3,4,5-tetrahydro-1H-benzazepine as the major product.
- Hill, John,Zakaria, Marwan M.,Mumford, David
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p. 2455 - 2458
(2007/10/02)
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- DIISOBUTYLALUMINIUM HYDRIDE A NOVEL REAGENT FOR THE REDUCTION OF OXIMES
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A simple procedure for converting oximes to rearranged secondary amines is described.
- Sasatani, Satoru,Miyazaki, Tohru,Maruoka, Keiji,Yamamoto, Hisashi
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p. 4711 - 4712
(2007/10/02)
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