- Cu-Catalyzed C-H Allylation of Benzimidazoles with Allenes
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CuH-catalyzed intramolecular cyclization and intermolecular allylation of benzimidazoles with allenes have been described. The reaction proceeded smoothly with the catalytic system of Cu(OAc)2/Xantphos and catalytic amount of (MeO)2MeSiH. This protocol features mild reaction conditions and a good tolerance of substrates bearing electron-withdrawing, electron-donating, or electron-neutral groups. A new catalytic mechanism was proposed for this copper hydride catalytic system.
- Dong, Yaxi,Breit, Bernhard
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p. 6765 - 6769
(2021/09/11)
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- Lysophosphatidic acid receptor antagonists and preparation method thereof
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The invention belongs to the technical field of medicinal chemistry, and particularly relates to lysophosphatidic acid receptor antagonists and a preparation method thereof. The applicant surprisinglyfinds that compounds provided by the invention have high LPAR1 antagonistic activity and selectivity, low toxicity, good metabolic stability and good drug development prospect, and can be used for preventing or treating diseases or symptoms related to LPAR1. The applicant also accidentally finds that the IC50 value of part of the compounds can be as low as 300 nM or below and even 50 nM or below.Moreover, the compounds disclosed by the invention have better safety, and the CC50 range of the compounds can reach 200 [mu]M or above. In addition, the compounds of the present invention have goodmetabolic stability in humans, rats, and mice, such excellent inhibitory activity being very desirable for their use as LPAR1 inhibitors in the above diseases or disorders. In addition, the preparation method of the compounds is simple, mild in reaction condition, high in product yield and suitable for industrial production.
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Paragraph 0681-0682; 0683-0685
(2020/07/29)
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- INHIBITORS OF VAP-1
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Provided herein are compounds and methods of use thereof for the modulation of VAP-1 activity.
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Paragraph 0446
(2020/05/12)
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- ERBB RECEPTOR INHIBITORS
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Disclosed are compounds inhibiting ErbBs (e. g. HER2), pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compound and the pharmaceutical composition can effectively treat diseases associated ErbBs (especially HER2), including cancer.
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Page/Page column 55
(2019/11/28)
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- Development of a Selective Inhibitor of Protein Arginine Deiminase 2
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Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis, and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the
- Muth, Aaron,Subramanian, Venkataraman,Beaumont, Edward,Nagar, Mitesh,Kerry, Philip,McEwan, Paul,Srinath, Hema,Clancy, Kathleen,Parelkar, Sangram,Thompson, Paul R.
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supporting information
p. 3198 - 3211
(2017/04/19)
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- Amino Azaxylylenes Photogenerated from o-Amido Imines: Photoassisted Access to Complex Spiro-Poly-Heterocycles
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Upon irradiation, cyclic imines containing o-amido groups are shown to produce reactive intermediates, amino azaxylylenes, which undergo intramolecular cycloadditions to tethered unsaturated pendants to yield complex N,O-heterocycles having an additional spiro-connected nitrogen heterocyclic moiety. Modular assembly of the photoprecursors allows expeditious increase of the complexity of the target poly-heterocyclic scaffolds with a minimal number of experimentally simple reaction steps. The photocyclization and subsequent postphotochemical transformations are accompanied by an increase of Lovering's fsp3 factor, thus producing unprecedented three-dimensional molecular architectures, and offering extended sampling of chemical space. Rings in three dimensions: Cyclic imines containing an o-amido group undergo excited-state intramolecular proton transfer to generate amino azaxylylenes. The amino azaxylylenes undergo intramolecular cycloadditions to tethered unsaturated pendants to yield complex heterocyclic three-dimensional molecular architectures.
- Mukhina, Olga A.,Kuznetsov, Dmitry M.,Cowger, Teresa M.,Kutateladze, Andrei G.
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supporting information
p. 11516 - 11520
(2015/11/03)
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- IRE-1α INHIBITORS
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PROBLEM TO BE SOLVED: To provide compounds which directly inhibit inositol requiring enzyme 1 (IRE-1α activity) in vitro, prodrugs, and pharmaceutically acceptable salts thereof. SOLUTION: The present invention provides a compound represented by formula (A) [R3 and R4 are H or the like; Q5-Q8, together with the benzene ring to which they are attached, form a benzofused ring, where at least one of Q5-Q8 is a heteroatom selected from N, O, and S. COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 1318; 1319
(2016/10/07)
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- ALDOSTERONE SYNTHASE INHIBITORS
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The invention involves compounds of structural Formula (I) and the pharmaceutically acceptable salts thereof. The compounds of the invention are effective at selectively inhibiting CYP11B2, and are therefore useful for the treatment or prophylaxis of disorders that are associated with elevated aldosterone levels, including, but not limited to, hypertension and heart failure.
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Page/Page column 95
(2012/02/05)
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- Benzimidazole- and benzothiazole-quinones: Excellent substrates for NAD(P)H:quinone oxidoreductase 1
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A series of benzimidazole- and benzothiazole-quinones has been synthesized. The ability of these heterocyclic quinones to act as substrates for recombinant human NAD(P)H:quinone oxidoreductase (NQO1), a two-electron reductase upregulated in tumour cells,
- Newsome, Jeffery J.,Colucci, Marie A.,Hassani, Mary,Beall, Howard D.,Moody, Christopher J.
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p. 3665 - 3673
(2008/09/21)
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- Therapeutic diphenyl ether ligands
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This invention is directed to compounds of formula Ia, Ib or Ic and to pharmaceutical compositions thereof: or a prodrug thereof and a pharmaceutically acceptable carrier, wherein the R groups are defined in the specification; and, in which the dashed line represents an optional double bond. The invention is also directed to methods of treating, diagnosing, and preventing disorders of the central nervous system that are associated with 5HT receptors, including obesity, attention deficit disorder, migraine, depression, epilepsy, anxiety, Alzheimer's disease, withdrawal from drug abuse, pain, schizophrenia, stress-related disorders, panic disorder, sleep disorders, phobias, obsessive compulsive disorder, post-traumatic-stress syndrome, immune system depression, stress-induced gastrointestinal dysfunction, stress-induced cardiovascular dysfunction, and sexual dysfunction.
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Page/Page column 35
(2010/10/20)
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- Selective one-pot N-monomethylation of 2-nitroanilines under PTC conditions
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Direct PTC methylation of 2-nitroanilines with dimethyl sulfate gave selectively N-monomethylated products. A variety of N-methyl-2-nitroanilines were prepared in this way.
- Voskresensky,Makosza
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p. 3523 - 3526
(2007/10/03)
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- Benzimidazole derivatives, their preparation and their therapeutic use
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Compounds of formula (I): STR1 [wherein: X represents an optionally substituted benzimidazole group; Y represents an oxygen or sulfur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxooxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethlyl group; R represents hydrogen, alkyl, alkoxy, halogen, hydroxy, nitro, amino or aralkyl; and m is an integer from 1 to 5]; have valuable activity for the treatment and/or prophylaxis of a variety of disorders, including one or more of: hyperlipemia, hyperglycemia, obesity, impaired glucose tolerance (IGT), insulin resistance and diabetic complications.
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- Synthesis and stability of 5-, 7- and 8-substituted benzo-1,2,3,5-tetrazepin-4-ones
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In order to determine the effect of substituents on the stability of benzo-fused 1,2,3,5-tetrazepin-4-ones, 5-, 7- and 8-substituted derivatives (6a-d), and (10) were synthesized. The stability of the tetrazepinones increased with the electron withdrawing character of the substituents at the benzene ring. Bulky groups at the 5 position destabilize the tetrazepinone ring. The unstable tetrazepinones (6b, 10 and 14) decomposed in chloroform at room temperature to benzotriazole derivatives (11, 12 and 15). X-Ray diffraction of nitrobenzotetrazepinone (6d) showed that despite the elctron withdrawing effect of the nitro group para to the triazene chain, N3 exhibited a significant pyramidal character. In 6d, the 1,2,3,5-tetrazepinone cycle has an almost perfect seven-membered ring boat shape.
- Jean-Claude, Bertrand J.,Just, George
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p. 1347 - 1363
(2007/10/03)
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- Thermal decomposition of arylnitramines
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The thermal decomposition of various substituted N-methyl-N-nitroanilines dissolved in indifferent solvents and piperidine has been investigated. Activation volumes and product analyses support evidence that the rate-determining step is the reversible homolysis of the nitramine bond. The activation volumes range from +18 to +36 ml mol-1. A non-linear Hammett relationship is attributed to an increase in secondary caged reactions, namely rearrangement and oxidation. Arylnitramines with electron-donating substituents yield greater amounts of the thermal rearrangement products than those with electron-deactivating groups at ambient pressures. Decomposition of arylnitramines with electron-donating substituents under high pressures (ca. 1.2 GPa) favours caged reactions over separative diffusion.
- Naud, Darren L.
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p. 1321 - 1324
(2007/10/03)
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- Benzimidazole derivatives, their preparation and their therapeutic use
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Compounds of formula (I): [in which: X represents an optionally substituted benzimidazole group; Y represents an oxygen or sulphur atom; Z represents a 2,4-dioxothiazolidin-5-ylidenylmethyl, 2,4-dioxothiazolidin-5-ylmethyl, 2,4-dioxo-oxazolidin-5-ylmethyl, 3,5-dioxooxadiazolidin-2-ylmethyl or N-hydroxyureidomethyl group; R represents hydrogen, alkyl, alkoxy, halogen, hydroxy, nitro, amino or aralkyl; and mis an integer from 1 to 5]; have valuable activity for the treatment and/or prophylaxis of a variety of disorders, including one or more of: hyperlipemia, hyperglycemia, obesity, impaired glucose tolerance (IGT), insulin resistance and diabetic complications.
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- A 'one-pot' phase transfer alkylation/hydrolysis of o-nitrotrifluoroacetanilides. A convenient route to N-alkyl o-phenylenediamines
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A variety of o-nitrotrifluoroacetanilides undergo a one-pot alkylation/hydrolysis to give N-alkyl o-nitroanilines in 40-94% yield. Dimethylsulfate, benzyl bromide and 1-bromo-propane were used as the electrophiles.
- Brown, Samuel A.,Rizzo, Carmelo J.
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p. 4065 - 4080
(2007/10/03)
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- New Routes to Selectively Methylated Benzimidazoles
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The use of intermediate benzotriazol-1-yl derivatives simplified the procedures for the preparation of 5-methoxy-1-methylbenzimidazole and 6-methoxy-1-methylbenzimidazole starting from 4-methoxy-2-nitroaniline.This strategy represents a novel and potentia
- Katritzky, Alan R.,Rachwal, Stanislaw,Ollmann, Richard
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p. 775 - 780
(2007/10/02)
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- Investigation of the Potential of Molybdenum(VI) Hydrazido(2-) Complexes as Sources of Nitrenium Ions: Cleavage of the N-N Bond and Incorporation of the β-Nitrogen Group into Solvent Molecules
-
Photolyis or thermolysis of bis(N,N-dimethyldithiocarbamato)bismolybdenum(VI) complexes in 1,1,2,2-tetrachloroethane results predominantly in transfer of the hydrazido group to the solvent with formation of dichloroacetohydrazides.A small amount of the corresponding dichloroacetamides are produced by N-N cleavage and N(R)Ph transfer.In contrast, the latter process dominates the reaction of dichlorobis(N,N-dimethyldithiocarbamato)mono-molybdenum(VI) complexes with silver nitrate in alcohols occuring concomitantly with ring methoxylation and nitration and N-nitrosation.Neither transfer of N(R)Ph appears to involve free nitrenium ions.
- Baum, Marc M.,Smith, Edward H.
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p. 2513 - 2520
(2007/10/02)
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- Reaction of a Molybdenum Hydrazido(2-) Complex with Silver Nitrate in Alcohols. Novel Variant of the Bamberger Reaction involving Concomitant N-Nitrosation
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Treatment of dichlorobis(dimethyldithiocarbamato)molybdenum(VI) with silver nitrate (3.3 equiv.) in alcoholic solvents results in cleavage of the hydrazido ligand from the metal to form p-alkoxyaniline derivatives.
- Baum, Marc M.,Smith, Edward H.
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p. 431 - 432
(2007/10/02)
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- Intramolecular Hydrogen Bonding in Some ortho-Substituted N-Methyl-, N-Benzyl- and N-Aryl-4-nitroanilines: a Proton Magnetic Resonance Study
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1H n.m.r. spectra of a wide variety of N-methyl, N-benzyl and N-aryl 2-substituted 4-nitroanilines where the 2-substituent is an electron-withdrawing group, namely acetyl, cyano, formyl or methoxycarbonyl, reveal that long-range coupling (5J 0.65-0.70 Hz) occurs between the NH proton and the 5-proton of the nitroaryl ring in (D)chloroform solution; coupling is absent when the 2-substituent is trifluoromethyl.However, for some compounds (the nature of the 2-substituent is critical), NH,H5 coupling is absent in (D6)dimethyl sulfoxide solution.An examination of these phenomena leads to the conclusion (a) that intramolecular hydrogen bonding occurs between the NH group and the 2-substituent and (b) that, for these N,2-substituted 4-nitroanilines, the intramolecular hydrogen bond strength decreases in the following order: NH...COOCH3 > NH...NO2 ca.NH...COCH3 > NH...CHO > NH...CN A parallel study involving some N-methyl 4-substituted 2-nitroanilines where the 4-substituent is an electron-donating group, namely t-butyl, methyl and methoxy, revealed long-range NH,H5 coupling in both (D)chloroform and (D6)dimethyl sulfoxide solution; when the substituent is dimethylamino, NH,H5 coupling could not be detected in either solvent.
- Wilshire, John F. K.
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p. 2497 - 2504
(2007/10/02)
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