- PYRROLIDINE DERIVATIVES AS INHIBITOR OF FIBROBLAST ACTIVATION PROTEIN (FAP) AND PHARMACEUTICAL COMPOSITION INCLUDING THE SAME
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The FAP inhibitor is represented by the following formula X. The present invention relates to a pyrrolidine derivative or a pharmaceutically acceptable salt thereof. Chem. X.
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Paragraph 3508; 3512-3514
(2020/11/24)
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- Synthesis of 2-bromo-and 2-phenyl-neo-confused porphyrins
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Neo-confused porphyrins (neo-CPs), porphyrin isomers with a 1,3-connected pyrrolic subunit, are aromatic structures with a CNNN coordination core. Previously, examples of neo-CPs with fused benzo units or electron-withdrawing ester substituents have been
- Almejbel, Arwa S.,Lash, Timothy D.
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p. 7336 - 7344
(2020/10/13)
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- Design, synthesis and RON receptor tyrosine kinase inhibitory activity of new head groups analogs of LCRF-0004
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New heteroarylcarboxamide head groups substituted with two aromatic rings analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent inhibitors of RON tyrosine kinase with various level of selectivity for c-Met RTK were obtained.
- Raeppel, Franck,Raeppel, Stéphane L.,Therrien, Eric
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p. 3810 - 3815
(2015/08/24)
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- Proton pump inhibitors
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A proton pump inhibitor containing a compound represented by the formula (I) wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 carbon atoms in the main chain, R 1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R 2 , R 3 and R 4 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, R 5 and R 6 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, which has a superior proton pump action and shows an antiulcer activity and the like after conversion to a proton pump inhibitor in the body, or a salt thereof. or a prodrug thereof is provided.
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- Development of a gold-multifaceted catalysis approach to the synthesis of highly substituted pyrroles: Mechanistic insights via Huisgen cycloaddition studies
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A novel gold-catalyzed method for the regioselective synthesis of highly substituted pyrroles directly from oximes and alkynes was developed via independent optimization of two key steps of the process. Importantly, a cationic gold(I) species was shown to activate multiple steps along the reaction pathway and therefore act as a multifaceted catalyst. Initial gold-promoted addition of the oxime oxygen to the activated alkyne afforded the O-vinyloxime in situ. The O-vinyloxime was subsequently transformed into the pyrrole via a gold-catalyzed tautomerization, [3,3]-sigmatropic rearrangement, and cyclodehydration process. Notably, this method provides a functional group handle in the form of an ester at the 3/4-position for further exploitation. The proposed mechanistic pathway is supported by a novel application of the Huisgen cycloaddition click reaction, which was used to probe the relative stability of substituted O-vinyloximes. The intermediacy of N-alkenylhydroxylamine O-vinyl ethers and imino ketones or imino aldehydes along the reaction pathway were determined by high-temperature 1H, 2H{1H}, and 13C{1H} NMR experiments. X-ray crystallographic evidence was used to further support the mechanistic hypothesis.
- Ngwerume, Simbarashe,Lewis, William,Camp, Jason E.
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p. 920 - 934
(2013/04/10)
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- Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3- ylsulfonyl)-1 H -pyrrol-3-yl]- n -methylmethanamine fumarate (tak-438) as a Potassium-Competitive Acid Blocker (P-CAB)
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In our pursuit of developing a novel and potent potassium-competitive acid blocker (P-CAB), we synthesized pyrrole derivatives focusing on compounds with low log"‰D and high ligand-lipophilicity efficiency (LLE) values. Among the compounds synthesized, the compound 13e exhibited potent H +,K+-ATPase inhibitory activity and potent gastric acid secretion inhibitory action in vivo. Its maximum efficacy was more potent and its duration of action was much longer than those of proton pump inhibitors (PPIs). Therefore, compound 13e (1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)- 1H-pyrrol-3-yl]-N-methylmethanamine fumarate, TAK-438) was selected as a drug candidate for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer, and other acid-related diseases.
- Arikawa, Yasuyoshi,Nishida, Haruyuki,Kurasawa, Osamu,Hasuoka, Atsushi,Hirase, Keizo,Inatomi, Nobuhiro,Hori, Yasunobu,Matsukawa, Jun,Imanishi, Akio,Kondo, Mitsuyo,Tarui, Naoki,Hamada, Teruki,Takagi, Terufumi,Takeuchi, Toshiyuki,Kajino, Masahiro
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p. 4446 - 4456
(2012/07/28)
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- Discovery, synthesis, and biological evaluation of novel pyrrole derivatives as highly selective potassium-competitive acid blockers
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To discover a gastric antisecretory agent more potent than existing proton pump inhibitors, novel pyrrole derivatives were synthesized, and their H +,K+-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 17a exhibited selective and potent H +,K+-ATPase inhibitory activity through reversible and K+-competitive ionic binding; furthermore, compound 17c exhibited potent inhibitory action on histamine-stimulated gastric acid secretion in rats and Heidenhain pouch dogs.
- Nishida, Haruyuki,Hasuoka, Atsushi,Arikawa, Yasuyoshi,Kurasawa, Osamu,Hirase, Keizo,Inatomi, Nobuhiro,Hori, Yasunobu,Sato, Fumihiko,Tarui, Naoki,Imanishi, Akio,Kondo, Mitsuyo,Takagi, Terufumi,Kajino, Masahiro
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p. 3925 - 3938
(2012/08/14)
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- Gold-catalysed rearrangement of O-vinyl oximes for the synthesis of highly substituted pyrroles
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O-Vinyl oximes were synthesised from the reaction of oximes with activated alkynes and subsequently rearranged using gold catalysis to afford highly substituted pyrroles in an efficient and regiocontrolled process. Additionally, pyrroles were formed direc
- Ngwerume, Simbarashe,Camp, Jason E.
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supporting information; experimental part
p. 1857 - 1859
(2011/03/23)
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- Synthesis of highly substituted pyrroles via nucleophilic catalysis
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Figure presented. A nucleophilic catalysis method providing a concise synthesis of di-, tri-, and tetrasubstituted pyrroles is described. This regioselective one-pot method relies on nucleophilic catalysis of the intermolecular addition of oximes to activ
- Ngwerume, Simbarashe,Camp, Jason E.
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supporting information; experimental part
p. 6271 - 6274
(2010/11/19)
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- Acid secretion inhibitor
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The present invention provides a compound having a superior acid secretion inhibitory effect and showing an antiulcer activity and the like. The present invention provides a compound represented by the formula (I) wherein R1 is a nitrogen-containing monocyclic heterocyclic group optionally condensed with a benzene ring or a heterocycle, the nitrogen-containing monocyclic heterocyclic group optionally condensed with a benzene ring or a heterocycle optionally has substituent(s), R2 is an optionally substituted C6-14 aryl group, an optionally substituted thienyl group or an optionally substituted pyridyl group, R3 and R4 are each a hydrogen atom, or one of R3 and R4 is a hydrogen atom and the other is an optionally substituted lower alkyl group, an acyl group, a halogen atom, a cyano group or a nitro group, and R5 is an alkyl group or a salt thereof.
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Page/Page column 21
(2008/06/13)
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- PROTON PUMP INHIBITORS
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A proton pump inhibitor containing a compound represented by the formula (I) wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 carbon atoms in the main chain, R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R2, R3 and R4 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, R5 and R6 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, which has a superior proton pump action and shows an antiulcer activity and the like after conversion to a proton pump inhibitor in the body, or a salt thereof. or a prodrug thereof is provided.
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- PROTON PUMP INHIBITORS
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Proton pump inhibitors which have excellent proton pumping activity and which can be converted in vivo into proton pump inhibitors to exhibit antiulcer effect and so on, containing compounds represented by the general formula (I) or salts thereof or prodrugs of the same: (I) wherein X and Y are each independently a free valency or a spacer whose main chain has 1 to 20 carbon atoms; R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; R2, R3 and R4 are each independently hydrogen, an optionally substituted hydrocarbon group, optionally substituted thienyl, optionally substituted benzo[b]thienyl, optionally substituted furyl, optionally substituted pyridyl, optionally substituted pyrazolyl, optionally substituted pyrimidinyl, acyl, halogeno, cyano, or nitro; and R5 and R6 are each independently hydrogen or an optionally substituted hydrocarbon group.
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Page/Page column 97; 285
(2010/10/20)
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- Synthesis of substituted pyrroles from N-vinylic phosphazenes derived from β-amino acids and α-bromo ketones
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Synthesis of di-, tri- and tetrasubstituted pyrroles by reaction of Nvinylic phosphazenes derived from β-amino acids with α-bromo ketones is described.
- Palacios, Francisco,Herran, Esther,Rubiales, Gloria
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- Flash vacuum pyrolysis of N-alkenylbenzotriazoles and N-alkenylisoxazolones
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The flash vacuum pyrolysis of 1-(2-ethoxycarbonylethenyl)benzotriazole has been reinvestigated, and the processes leading to the formation of ethyl indole-3-carboxylate and 2-ethoxyquinolin-4(1H)-one elucidated. Similar pathways are followed in the flash vacuum pyrolysis of the corresponding benzisoxazolone. Some N-ethenylisoxazolones have been pyrolysed to form pyrroles, but rearrangement of the intermediate carbenes may be observed. Photolysis of the isoxazolones gives carbenes that may be captured by solvent or give pyrroles. CSIRO 2000.
- Cox, Matthew,Heidarizadeh, Fariba,Pragei, Rolf H.
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p. 665 - 671
(2007/10/03)
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- Synthesis and dopamine D2-like receptor binding affinity of substituted 5-phenyl-pyrrole-3-carboxamides.
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A series of 5-p-substituted phenyl-pyrrole-3-carboxamide derivatives was designed as hybrid analogs of the dopamine D2-like 5-phenyl-pyrrole and heterocyclic carboxamide antipsychotics. The title compounds were synthesized and evaluated for dopamine D2-like receptor by means of [3H]YM-09151-2 receptor binding assay. The compound bearing a 1-ethyl-2-methyl-pyrrolidine moiety as the basic part of 5-phenyl-pyrrole-3-carboxamide derivative 1a together with its 2-chloro analog 1f were found to possess affinity in the low micromolar range. Substituted phenyl-pyrrolecarboxamides containing groups such as F, Cl, NO2, CH3, at the 4-position of the phenyl ring, gave ligands with lower D2-like affinity.
- Pinna,Curzu,Sechi,Chelucci,Maciocco
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p. 542 - 550
(2007/10/03)
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- 4-Substituted 2-phenyl- and 2-phenyl-3-aryl pyrroles by reaction of tosyl benzyl isocyanide (TosBIC) with Michael acceptors
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Synthesis of 2-phenyl and 2,3-diphenylpyrroles bearing at the 4 position electronwithdrawing groups by reaction of tosylbenzylisocyanide (TosBIC) with various Michael acceptors was investigated. Sodium hydride and n-butyllithium were used as deprotonating agents for the synthesis of monophenyl and diphenylpyrroles, respectively.
- Di Santo,Costi,Massa,Artico
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p. 795 - 802
(2007/10/02)
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