- Process Optimization for the Large-Scale Preparation of (2 S,3 aR,7 aS)- tert-Butyl Hexahydro-2,5-methanopyrrolo[3,2- c]pyridine-1(4 H)-carboxylate, an Intermediate for Nicotinic Acetylcholine Receptor Agonists
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An optimized large-scale synthesis of (2S,3aR,7aS)-tert-butyl hexahydro-2,5-methanopyrrolo[3,2-c]pyridine-1(4H)-carboxylate (1A), an important intermediate for nicotinic acetylcholine receptor agonists, is described. The key feature of the synthesis involves three transformations in a one-pot process, including debenzylation and ring hydrogenation of two fused bicyclic rings. Multihundred gram quantities of 1A were prepared.
- Jarugu, Lokesh Babu,Reddy, China Anki,Chikkananjunda, Nanjundaswamy Kanikahalli,Krishnamoorthy, Suresh,Sarvanakumar, Pon,Sankar, Ulaganathan,Arunachalam, Pirama Nayagam,McDonald, Ivar M.,Olson, Richard E.,Rampulla, Richard,Mathur, Arvind,Gupta, Anuradha
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supporting information
p. 1276 - 1281
(2018/09/25)
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- A threonine turnstile defines a dynamic amphiphilic binding motif in the AAA ATPase p97 allosteric binding site
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The turnstile motion of two neighboring threonines sets up a dynamic side chain interplay that can accommodate both polar and apolar ligands in a small molecule allosteric protein binding site. A computational model based on SAR data and both X-ray and cr
- Burnett, James C.,Lim, Chaemin,Peyser, Brian D.,Samankumara, Lalith P.,Kovaliov, Marina,Colombo, Raffaele,Bulfer, Stacie L.,LaPorte, Matthew G.,Hermone, Ann R.,McGrath, Connor F.,Arkin, Michelle R.,Gussio, Rick,Huryn, Donna M.,Wipf, Peter
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supporting information
p. 4096 - 4114
(2017/07/10)
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- AMIDO-BENZYL SULFONE AND SULFOXIDE DERIVATIVES
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The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.
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Page/Page column 133; 134
(2013/09/12)
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- PYRIDINYL AND PYRIMIDINYL SULFOXIDE AND SULFONE DERIVATIVES
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Disclosed are certain pyridinyl and pyrimidinyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds and methods of treatment using such compounds.
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Page/Page column 85
(2013/09/12)
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- AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES
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Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.
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Page/Page column 146; 147
(2013/09/12)
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- AMIDO-BENZYL SULFONE AND SULFONAMIDE DERIVATIVES
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Disclosed are certain amido-benzyl sulfone and sulfonamide compounds, pharmaceutical compositions comprising such compounds, land methods of treatment using such compounds.
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Page/Page column 63
(2013/09/12)
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- AMIDO-BENZYL SULFOXIDE DERIVATIVES
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The present invention relates to certain amido-benzyl sulfoxide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment of an NAMPT-mediated disease or condition in a subject, selected from solid or liquid tumor, rheumat
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Paragraph 0183
(2013/09/12)
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- ALKYL-AND DI-SUBSTITUTED AMIDO-BENZYL SULFONAMIDE DERIVATIVES
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The present invention relates to certain alkyl- and di-substituted amido-benzyl sulfonamide compounds, pharmaceutical compositions comprising such compounds, and to methods of treatment of NAMPT-mediated disorders, such as diabetes, rheumatoid arthritis,
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Paragraph 0191
(2013/09/12)
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- Potassium 4-iodylbenzenesulfonate: Preparation, structure, and application as a reagent for oxidative iodination of arenes
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A new hypervalent iodine(V) compound, potassium 4-iodylbenzenesulfonate, was prepared by the oxidation of 4-iodobenzensulfonic acid with Oxone in water. This potassium salt can be further converted into 4-iodylbenzenesulfonic acid by treatment with the acidic form of Amberlyst 15 in water. A single-crystal X-ray structure of potassium 4-iodylbenzenesulfonate revealed the presence of polymeric chains in the solid state due to a combination of numerous intra- and intermolecular interactions. Potassium 4-iodylbenzenesulfonate will likely find many practical applications as a thermally stable and water-soluble hypervalent iodine-based oxidant, particularly useful as a reagent for oxidative iodination of aromatic substrates. This reagent can be effectively recovered from the reaction mixture (92 % recovery) by treatment of the aqueous layer with Oxone at 60°C for 2 h, followed by filtration of the precipitate. A new hypervalent iodine(V) compound, potassium 4-iodylbenzenesulfonate, was prepared by oxidation of 4-iodobenzenesulfonic acid with Oxone in water. This new reagent promises many practical applications as a thermally stable, water-soluble and recyclable hypervalent iodine oxidant, particularly useful for oxidative iodination of aromatic substrates.
- Yusubov, Mekhman S.,Yusubova, Roza Y.,Nemykin, Victor N.,Maskaev, Andrey V.,Geraskina, Margarita R.,Kirschning, Andreas,Zhdankin, Viktor V.
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p. 5935 - 5942,8
(2020/09/02)
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- Palladium-catalyzed synthesis of 2,3-disubstituted 5-azaindoles via heteroannulation reaction and of 2-substituted 5-azaindoles through domino sila-Sonogashira/5-endo cyclization
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A general and efficient procedure for the synthesis of 2,3-disubstituted 5-azaindoles through the palladium-catalyzed heteroannulation of 4-acetamido-3-iodopyridines and diaryl-, dialkyl-, or arylalkylalkynes is described along with a study of the reactio
- Livecchi, Marion,Calvet, Geraldine,Schmidt, Frederic
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experimental part
p. 5006 - 5016
(2012/07/03)
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- Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis
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Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor-directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan- and tryptamine-derived natural product pathways.
- Lee, Hyang-Yeol,Yerkes, Nancy,O'Connor, Sarah E.
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scheme or table
p. 1225 - 1229
(2010/07/10)
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- AZA-BETA-CARBOLINES AND METHODS OF USING SAME
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Provided are compounds having the general structure according to Formula (I): Further provided are pharmaceutical compositions comprising these compounds. The invention still further provides methods of treating alcoholism, methods of reducing alcohol intake, methods of treating anhedonia, and methods of treating anxiety using theses compounds or the compositions containing them.
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Page/Page column 6-7; sheet 12
(2009/12/24)
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- INHIBITORS OF TRYPTASE
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The present invention related to certain inhibitors of tryptase that are inhibitors of tryptase, pharmaceutical composition comprising these compounds and method of treating asthma, allergic rhinitis, and/or Chronic Obstructive Pulmonary Disease utilizing these compounds.
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Page/Page column 153
(2008/06/13)
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- TETRACYCLIC INHIBITORS OF JANUS KINASES
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The present invention provides compounds that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases and cancer.
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Page/Page column 96
(2008/06/13)
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- Substituted pyrroline kinase inhibitors
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The present invention is directed to novel substituted pyrroline compounds useful as kinase or dual-kinase inhibitors and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.
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- Substituted oxoazaheterocyclyl compounds
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This invention is directed to oxoazaheterocycyl compounds which inhibit Factor Xa, to oxoazaheterocycyl compounds which inhibit both Factor Xa and Factor IIa, to pharmaceutical compositions comprising these compounds, to intermediates useful for preparing these compounds, to a method of directly inhibiting Factor Xa and to a method of simultaneously directly inhibiting Factor Xa and Factor IIa..
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Page/Page column 85-86
(2008/06/13)
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- CYCLOALKANEPYRROLOPYRIDINES AS DP RECEPTOR ANTAGONISTS
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Novel cycloalkanepyrrolopyridine derivatives are antagonists of prostaglandins, and as such are useful for the treatment of prostaglandin mediated diseases.
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- Discovery of an orally efficacious inhibitor of coagulation factor Xa which incorporates a neutral P1 ligand
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The discovery and SAR of ketopiperazino methylazaindole factor Xa inhibitors are described. Structure-activity data suggesting that this class of inhibitors does not bind in the canonical mode were confirmed by an X-ray crystal structure showing the neutral haloaromatic bound in the S1 subsite. The most potent azaindole, 33 (RPR209685), is selective against related serine proteases and attains higher levels of exposure upon oral dosing than comparable benzamidines and benzamidine isosteres. Compound 33 was efficacious in the canine AV model of thrombosis.
- Choi-Sledeski, Yong Mi,Kearney, Robert,Poli, Gregory,Pauls, Henry,Gardner, Charles,Gong, Yong,Becker, Michael,Davis, Roderick,Spada, Alfred,Liang, Guyan,Chu, Valeria,Brown, Karen,Collussi, Dennis,Leadley Jr., Robert,Rebello, Sam,Moxey, Phillip,Morgan, Suzanne,Bentley, Ross,Kasiewski, Charles,Maignan, Sebastien,Guilloteau, Jean-Pierre,Mikol, Vincent
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p. 681 - 684
(2007/10/03)
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- Azaindole derivatives and their use as therapeutic agents
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The present invention relates to compounds of the formula (I): wherein: Het represents a heterocyclic residue selected from: where the dotted line in (b) represents an optional double bond; A completes a fused pyridine ring; and B completes a fused benzene or pyridine ring. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migaine, emesis or postherpetic neuralgia.
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- Synthesis of novel heteroaromatics structurally related to ellipticine alkaloids via thermolysis of pyridannulated enyne-carbodiimides
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New synthetic pathways to the 5H-pyrido[3',4':4,5]pyrrolo[2,3-b]quinolines 6, the 6H-pyrido[3',4':4,5]pyrrolo[2,3-b] [1,6]naphthyridines 7, and the 11H-pyrido[43,3': 4,5]pyrrolo[2,3-b]quinolines 8 via thermolysis of the pyridannulated enyne-carbodiimides 14, 19, and 23 were established. These novel heteroaromatic systems are structurally related to ellipticine alkaloids and could serve as DNA- intercalating agents.
- Lu, Xiaoling,Petersen, Jeffrey L.,Wang, Kung K.
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p. 5412 - 5415
(2007/10/03)
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- 2-Aryl indole NK1 receptor antagonists: Optimisation of indole substitution
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The synthesis and biological evaluation of a series of 2-aryl indoles with high affinity for the human neurokinin-1 (hNK1) receptor are reported, concentrating on optimisation of the indole substitution.
- Cooper, Laura C.,Chicchi, Gary G.,Dinnell, Kevin,Elliott, Jason M.,Hollingworth, Gregory J.,Kurtz, Marc M.,Locker, Karen L.,Morrison, Denise,Shaw, Duncan E.,Tsao, Kwei-Lan,Watt, Alan P.,Williams, Angela R.,Swain, Christopher J.
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p. 1233 - 1236
(2007/10/03)
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- Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds
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The compounds of formula I herein exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More specifically, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, for treating a patient suffering from, or subject to, a physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.
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- Synthesis of new melatoninergic ligands including azaindole moiety
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A novel series of melatonin analogues, based on the azaindole nucleus is described. These compounds are prepared in several steps directly from the commercial available 7-azaindole or from substituted amino-, iodo- or/and nitropyridines using a catalysed palladium reaction or vicarious nucleophilic substitution of hydrogen (VNS) in order to elaborate the 6-, 5- and 4- azaindole derivatives respectively.
- Mazéas, Daniel,Guillaumet, Gérald,Viaud, Marie-Claude
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p. 1065 - 1080
(2007/10/03)
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