- Synthesis of Arylethylamines via C(sp3)-C(sp3) Palladium-Catalyzed Cross-Coupling
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Substituted arylethylamines represent a key structural motif in natural, pharmaceutical, and agrochemical compounds. Access to such scaffolds has been the subject of long-standing synthetic interest. Herein, we report the synthesis of such scaffolds via a palladium-catalyzed C(sp3)-C(sp3) coupling between (chloromethyl)aryls and air-/moisture-stable N,N-dialkylaminomethyltrifluoroborate salts. Rapid hit identification was achieved using microscale high-throughput experimentation and was followed by millimolar-scale reaction parameter optimization. A range of structurally and electronically varied arylethylamine products were obtained in moderate to excellent yields (27-96%, >60 examples). The reaction mechanism is proposed to proceed via formation of a trialkylbenzylammonium species prior to oxidative addition.
- Lippa, Rhys A.,Battersby, David J.,Murphy, John A.,Barrett, Tim N.
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p. 3583 - 3604
(2021/02/27)
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- Halogen-substituted latrotinib compound
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The invention relates to a halogen-substituted latrotinib compound. The halogen-substituted latrotinib compound comprises a latrotinib bisulfate compound labeled by a radioactive halogen atom or a non-radioactive halogen atom. The compound comprises a (R,
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Paragraph 0119; 0122-0125
(2021/02/10)
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- MONOCARBOXYLIC ACID TRANSPORTER 4 (MCT4) MODULATORS AND USES THEREOF
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Disclosed herein are compounds, compositions, and methods for modulating the monocarboxylic acid transporter 4 (MCT4) with the compounds and compositions disclosed herein. Also described are methods of treating diseases or conditions that are mediated by
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Paragraph 0223-0224
(2021/11/26)
-
- Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities
-
Accumulation of cytotoxic lipofuscin bisretinoids may contribute to atrophic age-related macular degeneration (AMD) pathogenesis. Retinal bisretinoid synthesis depends on the influx of serum all-trans-retinol (1) delivered via a tertiary retinol binding protein 4 (RBP4)-transthyretin (TTR)-retinol complex. We previously identified selective RBP4 antagonists that dissociate circulating RBP4-TTR-retinol complexes, reduce serum RBP4 levels, and inhibit bisretinoid synthesis in models of enhanced retinal lipofuscinogenesis. However, the release of TTR by selective RBP4 antagonists may be associated with TTR tetramer destabilization and, potentially, TTR amyloid formation. We describe herein the identification of bispecific RBP4 antagonist-TTR tetramer kinetic stabilizers. Standout analogue (±)-44 possesses suitable potency for both targets, significantly lowers mouse plasma RBP4 levels, and prevents TTR aggregation in a gel-based assay. This new class of bispecific compounds may be especially important as a therapy for dry AMD patients who have another common age-related comorbidity, senile systemic amyloidosis, a nongenetic disease associated with wild-type TTR misfolding.
- Cioffi, Christopher L.,Muthuraman, Parthasarathy,Raja, Arun,Varadi, Andras,Racz, Boglarka,Petrukhin, Konstantin
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p. 11054 - 11084
(2020/11/09)
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- Copper-Catalyzed Cross-Coupling between Alkyl (Pseudo)halides and Bicyclopentyl Grignard Reagents
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The development of a copper-catalyzed cross-coupling between primary and secondary (pseudo)halides and bicyclopentyl Grignard reagents is reported. Highly strained bicyclopentanes can be cross-coupled with a large panel of primary alkyl mesylates and secondary alkyl iodides. The catalytic system is simple and cheap, and the reaction is general and chemoselective.
- Andersen, Claire,Bernardelli, Patrick,Cossy, Janine,Daumas, Marc,Ferey, Vincent,Guérinot, Amandine
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supporting information
(2020/08/05)
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- Alkynyl-substituted heterocyclic compound, preparation method therefor and medical use therefor for effectively treating and/or preventing FGFR-related diseases such as tumors
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The present invention relates to an alkynyl-substituted heterocyclic compound serving as an FGFR inhibitor, a preparation method therefor and a medical use therefor. In particular, the present invention relates to a compound represented by the general formula (I) and its pharmaceutically acceptable salt, a pharmaceutical composition including the compound or its pharmaceutically acceptable salt, a method for treating and/or preventing FGFR-related diseases, particularly tumors, by using the compound or its pharmaceutically acceptable salt, and a preparation method of the compound or its pharmaceutically acceptable salt. The present invention also relates to an use of the compound or its pharmaceutically acceptable salt, or an pharmaceutical composition including the compound or its pharmaceutically acceptable salt in the preparation of a drug for treating and/or preventing FGFR-related diseases, particularly tumors, wherein the definition of each substituent in the general formula (I) is the same as that in the specification.
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Page/Page column 28-29
(2020/02/18)
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- C-3 NOVEL TRITERPENONE WITH C-28 AMIDE DERIVATIVES AS HIV INHIBITORS
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The invention relates to C-3 novel triterpenone with C-28 amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases (formula 1).
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-
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- SUBSTITUTED 5-CYANOINDOLE COMPOUNDS AND USES THEREOF
-
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for the treatment of lysine (K)-specific demethylase 1A (LSD1) - mediated diseases or disorders, Formula (I), wherein R1, R2, R3, R4, and R5 are as defined herein.
- -
-
Paragraph 00274; 00327
(2019/01/10)
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- Stereocontrolled C(sp3)-P bond formation with non-activated alkyl halides and tosylates
-
The C(sp3)-P bond is formed via the reaction between P-H compounds and non-activated alkyl electrophiles, especially secondary alkyl halides and tosylates. This reaction proceeds via an SN2 mechanism with inversion of configuration, so it can be used to form C-P bonds with stereocontrol from chiral secondary alcohols.
- Yang, Chu-Ting,Han, Jun,Liu, Jun,Li, Yi,Zhang, Fan,Gu, Mei,Hu, Sheng,Wang, Xiaolin
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p. 24652 - 24656
(2017/07/11)
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- HETEROAROMATIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
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Disclosed are heteroaryl derivatives, pharmaceutical composition and uses in the manufacture of a medicine for treating respiratory diseases, especially for chronic obstructive pulmonary disease (COPD).
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Paragraph 00468
(2016/05/02)
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- Aromatic heterocyclic derivatives and applications of aromatic heterocyclic derivatives in medicines
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The present invention discloses aromatic heterocyclic derivatives and applications of the aromatic heterocyclic derivatives in medicines, and specifically provides a class of aromatic heterocyclic compounds or stereoisomers, geometric isomers, tautomers, racemic bodies, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, and pharmaceutical compositions containing the compounds. The present invention further discloses uses of the compounds or pharmaceutical compositions in drug preparation, wherein the drug is used for treatment of respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).
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-
Paragraph 1487-1489
(2016/10/09)
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- 2-AMINO-BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS 5-LIPOXYGENASE AND/OR PROSTAGLANDIN E SYNTHASE INHIBITORS
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The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X1 and X2 are independently, at each occurrence, CR5 or N; Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups; R1 is selected from the group consisting of hydrogen, halogen, C1-C6 alkoxy, -NH2, -NHR6, -NR7R8 and -NH-(R9)n-R10, n being 0 or 1; R2 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, -NH2, -NHR6, - NR7R8 and -NH-(R9)n-R10; R3 is selected from the group consisting of hydrogen, hydroxyl, OR11, -NR7R8, C1-C6 alkoxy, C1-C6 alkyl, C3-C10 cycloalkyl, C1-C3 haloalkyl, -C(O)NHR11, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups; and R4 is selected from the group consisting of -NH2, -N(R12)(V)pR13, - NH(V)p-OR14, -NHC(O)R15, and groups of formula la shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease.
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Page/Page column 49; 50
(2016/03/12)
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- BIARYL COMPOUNDS USEFUL FOR THE TREATMENT OF HUMAN DISEASES IN ONCOLOGY, NEUROLOGY AND IMMUNOLOGY
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The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
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-
Paragraph 0407
(2015/06/25)
-
- Synthesis, characterization, and biological assessment of the four stereoisomers of the H3 receptor antagonist 5-fluoro-2-methyl-N-[2- methyl-4-(2-methyl[1,3′]bipyrrolidinyl-1′-yl)phenyl]benzamide
-
This Letter describes the asymmetric synthesis of the four stereoisomers (8a-8d) of a potent and highly selective histamine H3 receptor (H3R) antagonist, 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1, 3′]bipyrrolidinyl-1′-yl) phenyl]be
- Gao, Zhongli,Hurst, William J.,Guillot, Etienne,Nagorny, Raisa,Pruniaux, Marie-Pierre,Hendrix, James A.,George, Pascal G.
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p. 4044 - 4047
(2013/07/25)
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- A new solvent system (Cyclopentyl methyl ether-water) in process development of darifenacin HBr
-
Darifenacin is a potent and competitive M3 selective receptor antagonist (M3SRA), and its hydrobromide salt (1) is the active ingredient of pharmaceutical formulations for oral treatment of urinary incontinence. The present work demonstrates an efficient, commercial manufacturing process for darifenacin hydrobromide (1).
- Pramanik, Chinmoy,Bapat, Kiran,Chaudhari, Ashok,Tripathy, Narendra K.,Gurjar, Mukund K.
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p. 1591 - 1597
(2013/02/23)
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- Pyrimidine compounds and methods of making and using same
-
Disclosed herein are pyrimidinyl compounds that are contemplated to be modulators of cystic fibrosis transmembrane regulators (CFTR), and methods of making and using same. Also provided are pharmaceutical compositions and methods of treating disorders associated with cystic fibrosis transmembrane regulators, such as airway inflammation, cystic fibrosis, and the like.
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Page/Page column 57
(2013/02/27)
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- SUBSTITUTED N-HETEROARYL SPIROLACTAM BIPYRROLIDINES, PREPARATION AND THERAPEUTIC USE THEREOF
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The present invention discloses and claims a series of substituted N-heteroaryl spirolactam bipyrrolidines of formula ( Wherein R1, R2, Q1, Q2, Q3, Q4, X, m, n, p and s are as described her
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Page/Page column 33
(2011/12/02)
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- SUBSTITUTED N-PHENYL SPIROLACTAM BIPYRROLIDINES, PREPARATION AND THERAPEUTIC USE THEREOF
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The present invention discloses and claims a series of substituted N-phenyl spirolactam bipyrrolidines of formula (I). (Formula (I)) Wherein R1, R2, R3, R4, m, n, p and s are as described herein. More specifical
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Page/Page column 27
(2011/12/02)
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- SUBSTITUTED N-HETEROCYCLOALKYL BIPYRROLIDINYLPHENYL AMIDE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
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The present invention discloses and claims a series of substituted N- heterocycloalkyl bipyrrolidinylphenyl amide derivatives of formula (I). (Formula (I)) Wherein R, R1, R2, R3, R4, X, m, n and p are as describ
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Page/Page column 21-22
(2011/12/02)
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- SUBSTITUTED N-HETEROARYL BIPYRROLIDINE CARBOXAMIDES, PREPARATION AND THERAPEUTIC USE THEREOF
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The present invention discloses and claims a series of substituted N-heteroaryl bipyrrolidine carboxamides of formula (I). Wherein R1 R2, R3, R4, Q1, Q2, Q3, Q4, X, m
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Page/Page column 21-22
(2011/12/02)
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- SUBSTITUTED N-HETEROARYL TETRAHYDRO-ISOQUINOLINE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
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The present invention discloses and claims a series of substituted N-heteroaryl tetrahydro-isoquinoline derivatives of Formula (I). Wherein R, R1, R2, X, m, n and p are as described herein. More specifically, the compounds of this in
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Page/Page column 20-21
(2011/12/02)
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- SUBSTITUTED N-ALKYL AND N-ACYL TETRAHYDRO-ISOQUINOLINE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
-
The present invention discloses and claims a series of substituted N-alkyl and N-acyl tetrahydro-isoquinoline derivatives of formula (I). Wherein R, R1, R2, X, m, n and p are as described herein. More specifically, the compounds of t
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Page/Page column 23-24
(2011/12/02)
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- SUBSTITUTED PIPERIDINE SPIRO PYRROLIDINONE AND PIPERIDINONES USED AS H3 MODULATORS
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The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I), wherein R1, R2, R3, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptor
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Page/Page column 28-29
(2010/06/20)
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- HETEROCYCLIC COMPOUND
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The present invention relates to wherein each symbol is as defined in the specification. The compound of the present invention has a superior RBP4-lowering action, and is useful as a medicament for the prophylaxis or treatment of disease and condition mediated by increased RBP4.
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Page/Page column 46
(2010/07/08)
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- SUBSTITUTED TETRAHYDROPYRAN SPIRO PYRROLIDINONE AND PIPERIDINONE, PREPARATION AND THERAPEUTIC USE THEREOF
-
The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I) Wherein R1, R2, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefor.
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Page/Page column 34
(2010/06/20)
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- PROCESS FOR PREPARATION OF DARIFENACIN AND INTERMEDIATES USED IN THE PROCESS
-
Disclosed herein is a process for the preparation of darifenacin and physiologically acceptable salts thereof. Also disclosed is a compound of formula X: wherein R is linear or branched C 1-10 alkyl, phenyl, tolyl, ortho-, meta- or para- xylyl
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Page/Page column 19-20
(2010/04/25)
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- PROCESS FOR PRODUCING ESTER OR ALCOHOL
-
Provided is a process for producing an ester or alcohol using a fluoroimidinium sulfonate derivative represented by the general formula (9) or a fluoroimidinium carboxylate derivative represented by the general formula (6) and using as a raw material alcohol involving inversion of steric configuration. Further provided are a fluoroimidinium sulfonate derivative represented by the general formula (9), and a process for producing the same.
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Page/Page column 40-41
(2009/04/23)
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- SUBSTITUTED N-PHENYL-BIPYRROLIDINE CARBOXAMIDES AND THERAPEUTIC USE THEREOF
-
The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I), Wherein R, R1, R2, R3 and R4 are as described herein. More specifically, the compounds of th
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Page/Page column 31
(2009/05/28)
-
- SUBSTITUTED N-PHENYL-BIPYRROLIDINE UREAS AND THERAPEUTIC USE THEREOF
-
The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine ureas of formula (I) as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceuti
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Page/Page column 15; 25-26
(2009/05/28)
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- SUBSTITUTED N-PHENYL-BIPYRROLIDINE CARBOXAMIDES AND THERAPEUTIC USE THEREOF
-
The present invention discloses and claims a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I) as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as phar
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Page/Page column 15; 26-27
(2009/05/28)
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- METHOD AND COMPOSITIONS FOR TREATING HIV INFECTIONS
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Described herein are compounds and compositions that are useful in the treatment of HIV, AIDS, and AIDS-related diseases. In addition, compounds are described herein that are capable of inhibiting the dimerization of HIV proteases.
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Page/Page column 40
(2008/12/08)
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- INHIBITORS OF 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE 1
-
The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salts or solvates thereof, wherein n, X, Y, R1, R2, R3 and R4 are as described in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating conditions that are mediated by the modulation of 11 βHSD1 , the method comprising administering to a mammal an effective amount of a compound of formula (I).
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Page/Page column 28
(2010/11/25)
-
- Pyrrolopyrimidines as therapeutic agents
-
Chemical compounds having structural formula I and physiologically acceptable salts and metabolites thereof, are inhibitors of serine/threonine and tyrosine kinase activity. Several of the kinases, whose activity is inhibited by these chemical compounds, are involved in immunologic, hyperproliferative, or angiogenic processes. Thus, these chemical compounds can ameliorate disease states where angiogenesis or endothelial cell hyperproliferation is a factor. These compounds can be used to treat cancer and hyper proliferative disorders, rheumatiod arthritis, disorders of the immune system, trasplant refections and imflammatory disorders.
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-
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- Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them
-
A compound selected from the group consisting of a compound of the formula wherein A is selected from the group consisting of and the other substituents are defined in the specification having an inhibitory activity of NO-synthase enzymes producing nitrogen mono-oxide and/or an activity which traps the reactive oxygen species.
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Page column 102
(2008/06/13)
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- Heterocyclic compounds useful as NMDA receptor selective subtype blockers
-
The invention relates to compounds of formula wherein Ar1 is pyridyl or phenyl, substituted by hydroxy, lower alkyl, halogen, amino, nitro, benzyloxy or lower alkoxy-lower alkoxy, or is the group wherein Z1 is a five membered heteroc
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-
-
- 1-methylcarbapenem derivatives
-
A 1-methylcarbapenem compound represented by the following formula: STR1 [wherein R1 represents a hydrogen atom or a lower alkyl group, R2 represents a hydrogen atom or a lower alkyl group, R3 represents a hydrogen atom, a
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-
-
- Preparative and structural chemistry of chiral 3-(diphenylphosphanyl)pyrrolidines and their palladium(II) complexes
-
The preparation of both enantiomers of 3-diphenylphosphanylpyrrolidine (2) and several N-substituted derivatives together with two Pd complexes of this ligand is reported. From L-malic acid and L-hydroxyproline both enantiomers of 3-hydroxypyrrolidine are prepared without any problems due to epimerization. KPPh2 in the presence of LiCl is shown to be the most effective reagent for the synthesis of 2. The reported X-ray structure determinations of PdI2 complexes show a rather rigid bicyclic hetero-norbornane skeleton. The flexibility of the other parts of the molecules is obvious in several polymorphs revealed by this method. This polymorphism is additionally investigated by a 31P-CP-MAS study. From solution 'H-, 13C- and 31P-NMR studies it is concluded that the bicyclic hetero-norbornane skeleton is retained in solution. VCH Verlagsgesellschaft mbH.
- Nagel, Ulrich,Nedden, Hans Guenter
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p. 385 - 397
(2007/10/03)
-