- Functionalization of 2-Trifluoromethyl-1H-pyrrole: A Convenient Entry into Advanced Fluorinated Building Blocks Including all Isomeric 2-(Trifluoromethyl)prolines
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The synthetic utility of 2-trifluoromethyl-1H-pyrrole as a pharmaceutically relevant platform was demonstrated by the preparation of mono- and bifunctional C-2(5)- or C-3-substituted derivatives, i.e. regioisomeric sulfonyl halides, carboxylic acids, aldehydes, and nitriles. A series of modifications relied on lithiation or electrophilic substitution, which proceeded regioselectively on multigram scale, mostly in protecting-group-free mode. Subsequent catalytic hydrogenation of the pyrrole ring was also performed for synthesis of all isomeric 2-trifluoromethyl α- and β-prolines. These derivatives were considered as promising low-molecular-weight building blocks for synthesis, drug discovery, and agrochemistry.
- Hys, Vasyl Yu.,Shevchuk, Oleksandr I.,Vashchenko, Bohdan V.,Karpenko, Oleksandr V.,Gorlova, Alina O.,Grygorenko, Oleksandr O.
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- IMPROVED METHODS, KITS, COMPOSITIONS AND DOSING REGIMENS FOR THE USE OF HETEROCYCLIC INHIBITORS OF ERK1 AND ERK2
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The present application provides improved compositions, methods, kits and dosing regimens for the use of heterocyclic compounds and pharmaceutically acceptable salts, prodrugs, solvates, hydrates, or stereoisomers thereof. These compositions, methods, kit
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Page/Page column 101-102
(2021/05/07)
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- SULFONAMIDE COMPOUNDS AND THE USE THEREOF IN THE TREATMENT OF CANCER
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The present disclosure relates generally to a class of sulfonamide-based compounds, compositions containing the same and the therapeutic use of the compounds in the treatment of cancer.
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Paragraph 00181
(2021/04/23)
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- Metal-Free Directed C?H Borylation of Pyrroles
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Robust strategies to enable the rapid construction of complex organoboronates in selective, practical, low-cost, and environmentally friendly modes remain conspicuously underdeveloped. Here, we develop a general strategy for the site-selective C?H borylation of pyrroles by using only BBr3 directed by pivaloyl groups, avoiding the use of any metal. The site-selectivity is generally dominated by chelation and electronic effects, thus forming diverse C2-borylated pyrroles against the steric effect. The formed products can readily engage in downstream transformations, enabling a step-economic process to access drugs such as Lipitor. DFT calculations (wB97X-D) demonstrate the preferred positional selectivity of this reaction.
- Wang, Zheng-Jun,Chen, Xiangyang,Wu, Lei,Wong, Jonathan J.,Liang, Yong,Zhao, Yue,Houk, Kendall N.,Shi, Zhuangzhi
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supporting information
p. 8500 - 8504
(2021/03/16)
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- NOVEL OXADIAZOLE COMPOUNDS CONTAINING 5- MEMBERED HETEROAROMATIC RING FOR CONTROLLING OR PREVENTING PHYTOPATHOGENIC FUNGI
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The present invention relates to a compound of formula (I), wherein, R1,A, A5, A6, A7, A8, R12, n and Q are as defined in the detailed description and a process for preparing the compound of formula (I).The present invention also relates to a method for controlling or preventing phytopathogenic fungi.
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Page/Page column 74
(2021/02/26)
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- COMPOUNDS AND USES THEREOF
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The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
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Page/Page column 150
(2020/08/22)
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- Preparation method of 4-ethyl-1H-pyrrole-3-methyl carboxylate
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The invention discloses a preparation method of 4-ethyl-1H-pyrrole-3-methyl carboxylate, and belongs to the field of chemical engineering. The preparation method comprises following steps: 3-pyrrole methyl carboxylate preparation: taking concentrated sulfuric acid as a catalyst, adding 3-pyrrole carboxylic acid into a methanol solution, carrying out reactions for 2 to 4 hours at a temperature of 45 to 65 DEG C, continuously extracting 3-pyrrole methyl carboxylate to obtain 3-pyrrole methyl carboxylate according to the reaction balance principle; taking a mixture composed of anhydrous calcium chloride and nano alumina as a catalyst, heating to a temperature of 80 to 100 DEG C, adding ethane, stirring for 40 to 60 minutes, cooling to a temperature of 5 to 10 DEG C, allowing the system to stand still for 12 to 14 hours, subjecting the reaction liquid to vacuum concentration, re-crystallizing obtained solids in a mixed solvent, which is composed of ether and ethane according to a volume ratio of 1:1-2; and drying to obtain 4-ethyl-1H-pyrrole-3-methyl carboxylate. The preparation is simple, the method and principle are reasonable, and the preparation method is suitable for popularization and application.
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Paragraph 0013-0015
(2019/08/30)
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- HETEROCYCLIC INHIBITORS OF ERK1 AND ERK2 AND THEIR USE IN THE TREATMENT OF CANCER
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The present application provides novel heterocyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful for inhibiting ERK1/2. By administering to a patient in need a
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Paragraph 0459-0460
(2017/01/02)
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- Beneficial Effects of Electrochemistry in Cross-Coupling Reactions: Electroreductive Synthesis of 4-Aryl- or 4-Heteroaryl-6-pyrrolylpyrimidines
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The rarely described 4-(hetero)aryl-6-pyrrolylpyrimidines are prepared by electroreductive nickel-catalysed cross-coupling reactions between aryl halides and chloropyrimidines. Inherent predictable issues of such metal-catalysed reactions that involve or
- Sengmany, Stéphane,Vasseur, Stéphane,Lajnef, Abdelmoumen,Le Gall, Erwan,Léonel, Eric
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supporting information
p. 4865 - 4871
(2016/10/13)
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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, 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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Paragraph 0213
(2015/11/16)
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- FSH RECEPTOR ANTAGONISTS
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The invention relates to FSH receptor antagonist according to general formula (I) or a pharmaceutically acceptable salt thereof and to a pharmaceutical composition containing the same. The compounds can be used for the treatment and prevention of endometriosis, for the treatment and prevention of pre-menopausal and peri-menopausal hormone-dependent breast cancer, for contraception, and for the treatment of uterine fibroids and other menstrual-related disorders
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Page/Page column 92
(2013/04/10)
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- Regioselectivity in the intramolecular heck reaction of a series of cyclic sulfonamides: An experimental and computational study
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Regioselectivity in the intramolecular Heck reaction of a series of N-sulfonyl-2,5-dihydro-3-substituted pyrroles was studied. These substrates are unbiased in terms of the formed ring size of the new heterocycle. Results indicate that high levels of regi
- Geoghegan, Kimberly,Evans, Paul,Rozas, Isabel,Alkorta, Ibon
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supporting information
p. 13379 - 13387
(2012/11/07)
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- Molecular recognition at the active site of catechol-O-methyltransferase (COMT): Adenine replacements in bisubstrate inhibitors
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L-Dopa, the standard therapeutic for Parkinson's disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of an activated methyl group from S-adenosylmethionine (SAM) to its catechol substrates, such as L-dopa, in the presence of magnesium ions. The molecular recognition properties of the SAM-binding site of COMT have been investigated only sparsely. Here, we explore this site by structural alterations of the adenine moiety of bisubstrate inhibitors. The molecular recognition of adenine is of special interest due to the great abundance and importance of this nucleobase in biological systems. Novel bisubstrate inhibitors with adenine replacements were developed by structure-based design and synthesized using a nucleosidation protocol introduced by Vorbrueggen and co-workers. Key interactions of the adenine moiety with COMT were measured with a radiochemical assay. Several bisubstrate inhibitors, most notably the adenine replacements thiopyridine, purine, N-methyladenine, and 6-methylpurine, displayed nanomolar IC50 values (median inhibitory concentration) for COMT down to 6 nM. A series of six cocrystal structures of the bisubstrate inhibitors in ternary complexes with COMT and Mg2+ confirm our predicted binding mode of the adenine replacements. The cocrystal structure of an inhibitor bearing no nucleobase can be regarded as an intermediate along the reaction coordinate of bisubstrate inhibitor binding to COMT. Our studies show that solvation varies with the type of adenine replacement, whereas among the adenine derivatives, the nitrogen atom at position 1 is essential for high affinity, while the exocyclic amino group is most efficiently substituted by a methyl group. Copyright
- Ellermann, Manuel,Paulini, Ralph,Jakob-Roetne, Roland,Lerner, Christian,Borroni, Edilio,Roth, Doris,Ehler, Andreas,Schweizer, W. Bernd,Schlatter, Daniel,Rudolph, Markus G.,Diederich, Francois
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supporting information; experimental part
p. 6369 - 6381
(2011/08/06)
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- Therapeutic Compounds
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Compounds of formula I or pharmaceutically acceptable salts thereof: wherein R1, R2, R3 and R4 are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
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Page/Page column 28
(2011/04/25)
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- INHIBITORS OF AKT ACTIVITY
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Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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Page/Page column 56
(2008/12/08)
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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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- 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 22-23
(2008/06/13)
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- Therapeutic Compounds
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Compounds of formula I or pharmaceutically acceptable salts thereof: wherein R1, R2, R3 and R4 are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
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Page/Page column 28
(2008/06/13)
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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 115-116; 285
(2010/10/20)
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- Syntheses of imidazoles and pyrroles: Betmic and tosmic as complementary reagents
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p-Tolylsulfonylmethyl isocyanide (TosMIC) and benzotriazol-1-yl-methyl isocyanide (BetMIC) were compared as to their synthetic utilities for the synthesis of imidazoles and pyrroles and found to be complementary.
- Katritzky, Alan R.,Cheng, Dai,Musgrave, Richard P.
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- α-(Dialkylamino)-α-pyrrolylacetonitriles. A potpourri of useful synthetic transformations
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α-(Dialkylamino)-α-(pyrrol-2-yl)acetonitriles (3) are versatile intermediates that are readily converted into regiochemically pure 2-bromo-6-dialkylamino-1-azafulvenes and 5-bromo-2-acylpyrroles (acyl= CHO, COR).In addition, 3 (R1= H), 4 (R1= H), and the β-substituted compound 9 are transformed easily and under mild conditions, via the corresponding α-methylthio compounds (e.g., 7a), into the methyl pyrrole carboxylates 8a, 8b, and 10, respectively.
- Bray, Brian L.,Muchowski, Joseph M.
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p. 1305 - 1308
(2007/10/02)
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- Lithiations of 1-Trialkylsilylpyrroles: N to C Silyl Group Rearrangement
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The sites of metallation with alkyl-lithium reagents of 1-trimethylsilyl- and 1-triethylsilyl-pyrroles have been explored under a variety of conditions.With short reaction times, BunLi reacts with 1-trimethylsilylpyrrole in hexane predominantly at the 2-position though with ButLi in pentane the unusual 3-metallated product is preferred.During prolonged reaction of 1-trimethylsilyl- and 1-triethylsilyl-pyrroles with ButLi, the 2-monolithio- and the 2,4- and 2,5-dilithio-intermediates are formed, in which, unexpectedly, the silyl groups migrate to the pyrrole 2-position.Under conditions favouring enhanced ionicity, BunLi cleaves the N-SiMe3 bond in preference to ring metallation.
- Chadwick, Derek J.,Hodgson, Simon T.
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p. 1833 - 1836
(2007/10/02)
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- Antidiabetic pyrrolecarboxylic acids
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Certain pyrrolecarboxylic and pyrroleacetic acid derivatives substituted on the pyrrole ring with thioether groups, acyl groups, phenyl, substituted phenyl, phenoxy, substituted phenoxy, benzyl or halo and optionally substituted on the pyrrole nitrogen with alkyl, and the pharmaceutically acceptable salts thereof, are useful in lowering the blood glucose levels of hyperglycemic animals.
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- Pyrrole chemistry. XXII. A "one-pot" synthesis of some 4-acylpyrrole-2-carboxaldehydes from pyrrole
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The Vilsmeier-Haack intermediates formed from pyrrole and from 1-methylpyrrole may be acylated under normal Friedel-Crafts conditions.Hydrolytic work-up then gives 4-acylpyrrole-2-carboxaldehydes in good yield.The methoxide/methanol treatment of the 4-trichloroacetylated intermediate leads to methyl 2-formylpyrrole-4-carboxylate.These are all "one-pot" syntheses from pyrrole.The formyl group has been removed from several of the products thus affording some 3-acylpyrroles in two operations.
- Anderson, Hugh J.,Loader, Charles E.,Foster, Aidan
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p. 2527 - 2530
(2007/10/02)
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