- NOVEL SUBSTITUTED 1,3,8-TRIAZASPIRO[4,5]DECANE-2,4-DIONE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) AND/OR TRYPTOPHAN 2,3-DIOXYGENASE (TDO) INHIBITORS
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Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: (I). Also disclosed herein are uses of a compound disclosed herein in the potential treatment or prevention of an IDO- and/or TDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of a composition in the potential treatment or prevention of an IDO- and/or TDO-associated disease or disorder.
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Page/Page column 30-31
(2021/06/26)
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- PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR
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This invention relates to processes and intermediates for making {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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Paragraph 0107-0108
(2019/08/22)
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- Indolyl Azaspiroketal Mannich Bases Are Potent Antimycobacterial Agents with Selective Membrane Permeabilizing Effects and in Vivo Activity
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The inclusion of an azaspiroketal Mannich base in the membrane targeting antitubercular 6-methoxy-1-n-octyl-1H-indole scaffold resulted in analogs with improved selectivity and submicromolar activity against Mycobacterium tuberculosis H37Rv. The potency enhancing properties of the spiro-fused ring motif was affirmed by SAR and validated in a mouse model of tuberculosis. As expected for membrane inserting agents, the indolyl azaspiroketal Mannich bases perturbed phospholipid vesicles, permeabilized bacterial cells, and induced the mycobacterial cell envelope stress reporter promoter piniBAC. Surprisingly, their membrane disruptive effects did not appear to be associated with bacterial membrane depolarization. This profile was not uniquely associated with azaspiroketal Mannich bases but was characteristic of indolyl Mannich bases as a class. Whereas resistant mycobacteria could not be isolated for a less potent indolyl Mannich base, the more potent azaspiroketal analog displayed low spontaneous resistance mutation frequency of 10-8/CFU. This may indicate involvement of an additional envelope-related target in its mechanism of action.
- Nyantakyi, Samuel Agyei,Li, Ming,Gopal, Pooja,Zimmerman, Matthew,Dartois, Véronique,Gengenbacher, Martin,Dick, Thomas,Go, Mei-Lin
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supporting information
p. 5733 - 5750
(2018/06/20)
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- High-Temperature Boc Deprotection in Flow and Its Application in Multistep Reaction Sequences
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A simplified Boc deprotection using a high-temperature flow reactor is described. The system afforded the qualitative yield of a wide variety of deprotected substrates within minutes using acetonitrile as the solvent and without the use of acidic conditions or additional workups. Highly efficient, multistep reaction sequences in flow are also demonstrated wherein no extraction or isolation was required between steps.
- Bogdan, Andrew R.,Charaschanya, Manwika,Dombrowski, Amanda W.,Wang, Ying,Djuric, Stevan W.
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p. 1732 - 1735
(2016/05/19)
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- Design and synthesis of spirocyclic compounds as HCV replication inhibitors by targeting viral NS4B protein
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Two novel series of spirocyclic piperidine analogs appended to a pyrazolo[1,5-a]pyridine core were designed, synthesized and evaluated for their anti-HCV activity. A series of piperidine ketals afforded dispiro 6p which showed excellent in vitro anti-HCV activities (EC50 of 1.5 nM and 1.2 nM against genotype 1a and 1b replicons, respectively). A series of piperidine oxazolidinones afforded 27c which showed EC50's of 10.9 nM and 6.1 nM against 1a and 1b replicons, respectively. Both compounds 6p and 27c bound directly to non-structural NS4B protein in vitro (IC50's = 10.2 and 30.4 nM, respectively) and exhibited reduced potency in replicons containing resistance mutations encoding changes in the NS4B protein.
- Tai, Vincent W.-F.,Garrido, Dulce,Price, Daniel J.,Maynard, Andrew,Pouliot, Jeffrey J.,Xiong, Zhiping,Seal, John W.,Creech, Katrina L.,Kryn, Luz H.,Baughman, Todd M.,Peat, Andrew J.
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p. 2288 - 2294
(2014/05/20)
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- PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR
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This invention relates to processes and intermediates for making {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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Paragraph 0150
(2014/09/29)
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- PROCESSES AND INTERMEDIATES FOR MAKING A JAK INHIBITOR
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This invention relates to processes and intermediates for making {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, useful in the treatment of diseases related to the activity of Janus kinases (JAK) including inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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Page/Page column 29
(2013/03/26)
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- C-2 arylation of piperidines through directed transition-metal-catalyzed sp3 C-H activation
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All you need is an open vial! The direct α arylation of cyclic alkylamines (see scheme) requires an open vial, as the hydrogen atom involved in the C(sp3)-H-activation process is ultimately released as hydrogen gas. Reports on the formation of hydrogen gas in direct transition-metal- catalyzed functionalizations are still rare. Open-vial reactions proved crucial to this direct arylation procedure as, upon sealing, catalyst deactivation occurs.
- Prokopcova, Hana,Bergman, Sheba D.,Aelvoet, Karel,Smout, Veerle,Herrebout, Wouter,Van Der Veken, Benjamin,Meerpoel, Lieven,Maes, Bert U. W.
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supporting information; experimental part
p. 13063 - 13067
(2011/02/21)
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- 2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
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The present invention has its object to provide a 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented with the Formula (1) , or the pharmaceutically acceptable salt, which is effective as a therapeutic and prophylactic agent for diabetes, diabetic nephropathy, or glomerulosclerosis.
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- THIAZOLE DERIVATIVES AND USE THEREOF
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The present invention is related to thiazole derivatives of Formula (I) in particular for the treatment and/or prophylaxis of autoimmune disorders and/or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplantation, graft rejection or lung injuries.
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- Benzothiazole derivatives with activity as adenosine receptor ligands
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The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
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- Scavenger assisted combinatorial process for preparing libraries of amides, carbamates and sulfonamides
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This invention relates to a novel solution phase process for the preparation of amide, carbamate, and sulfonamide combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Preparation and in Vitro and in Vivo Evaluation of Quinolones with Selective Activity against Gram-Positive Organisms
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A series of quinolones were prepared which contained oximes or substituted oximes as replacements for the amine substituents normally found on the pyrrolidine or piperidine fragments of quinolone antibacterial agents.These substituents led to compounds that had selective activity against Gram-positive organisms.These compounds showed in vivo activity Staphylococcus aureus.Only compound 29 had in vivo activity against Streptococcus pneumoniae.
- Cooper, Curt S.,Klock, Pamela L.,Chu, Daniel T. W.,Hardy, Dwight J.,Swanson, Robert N.,Plattner, Jacob J.
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p. 1393 - 1398
(2007/10/02)
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- SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NEW 7-SUBSTITUTED FLUOROQUINOLONES
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Reaction of substitued 3-carboxyquinolone derivatives IIIa, IIIb, IIIc, and IV with 4-pyridone ethylene ketal in pyridine afforded corresponding 7-substituted derivatives VIa, VIb, VIc, and VIIa, respectively.Acidic deprotecion of these compounds yielded respective oxo derivatives VId, VIe, VIf, and VIIb which were converted to their oximes If, Ig, Ih, and IIb.
- Radl, Stanislav,Kovarova, Lenka
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p. 2406 - 2412
(2007/10/02)
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- Synthesis of the new α- and β-adrenergic antagonist 1-[1-(2-benzodioxanylmethyl)-4-piperidyl]amino-3-(1-naphthoxy)-2- propanol
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The synthesis and in vitro α- and β-adrenergic blocking potency of 1-[1-(2-benzodiaxanylmethyl)-4-piperidyl]amino-3-(1-naphthoxy)-2- propanol (I) are described. Thus, N-benzyl-4piperidone was protected and debenzylated to the carbamate (V), which upon alkaline hydrolysis and acylation gave benzodioxanic amide (IX). Reduction of the amide group, deprotection of the ketone function of (X), and reductive amination gave the 4-aminopiperidine (XIII), which was finally condensed with the appropriate epoxide to yield the aminopropanol (I). Compound (I) is formally derived from a combination of piperoxan (II) and propranolol (III), and was approximately 10 times less potent than each one of these drugs, as an α- and β-adrenergic blocker respectively.
- Mauleon,Antunez,Rosell
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p. 1109 - 1117
(2007/10/02)
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