- Synthesis of nitric oxide probes with fluorescence lifetime sensitivity
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We present the rationale, synthesis and evaluation of the first activatable fluorescent probe that utilizes fluorescence lifetime change for detection of nitric oxide. The new probe DAP-LT1 features a near-infrared polymethine skeleton with a diaminobenzene functionality incorporated into the meso-position. The probe is partially quenched, and upon reaction with nitric oxide shows an increase in the fluorescence lifetime from 1.08 ns to 1.24 ns.
- Zhegalova, Natalia G.,Gonzales, Garrett,Berezin, Mikhail Y.
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Read Online
- Spiroconjugated Tetraaminospirenes as Donors in Color-Tunable Charge-Transfer Emitters with Donor-Acceptor Structure
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Charge-transfer emitters are attractive due to their color tunability and potentially high photoluminescence quantum yields (PLQYs). We herein present tetraaminospirenes as donor moieties, which, in combination with a variety of acceptors, furnished 12 charge-transfer emitters with a range of emission colors and PLQYs of up to 99 %. The spatial separation of their frontier molecular orbitals was obtained through careful structural design, and two DA structures were confirmed by X-ray crystallography. A range of photophysical measurements supported by DFT calculations shed light on the optoelectronic properties of this new family of spiro-NN-donor-acceptor dyes.
- Grenz, David C.,Rose, Daniel,W?ssner, Jan S.,Wilbuer, Jennifer,Adler, Florin,Hermann, Mathias,Chan, Chin-Yiu,Adachi, Chihaya,Esser, Birgit
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supporting information
(2021/12/22)
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- 1H-BENZO[D]IMIDAZOLE DERIVATIVES AS TLR9 INHIBITORS FOR THE TREATMENT OF FIBROSIS
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The present invention relates to lH-benzo[d]imidazole derivatives of formula (I) or a salt thereof. The present compounds are inhibitors of TLR9 and useful in treating preventing, or slowing fibrotic diseases, such as e.g. liver fibrosis, renal fibrosis, biliary fibrosis or pancreatic fibrosis, nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC), or idiopathic pulmonary fibrosis (IPF).
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Page/Page column 74-75; 88
(2022/03/07)
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- INHIBITORS OF FIBROBLAST GROWTH FACTOR RECEPTOR KINASES
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Provided herein are heteroaryl inhibitors of fibroblast growth factor receptor kinases, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
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Paragraph 00546-00547
(2021/12/30)
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- 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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- 1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to 1,3,4-oxadiazole derivative compounds having a histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, a use thereof in preparation of a medicament, a pharmaceutical composition comprising the same, a therapeutic method using the composition, and a method for preparing the same, and the 1,3,4-oxadiazole derivative compounds are represented by a following chemical formula (I).
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Page/Page column 422-423
(2020/12/11)
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- Benzimidazole derivatives as potent and isoform selective tumor-associated carbonic anhydrase IX/XII inhibitors
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We describe the synthesis of a series of 2-arylbenzimidazole derivatives bearing sulfonamide functionality (4a–d, 7a–c and 10) as well as hydroxamic acid (15a–b), carboxylic acid (16a–b), carboxamide (17a–b) and boronic acid (22a–b and 26) functionalities, which act as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. The newly synthesized benzimidazole derivatives were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IX, and XII), and especially the sulfonamide-containing benzimidazoles demonstrated intriguing inhibitory activity against tumor associated CA IX and XII with KI values in the range of 5.2–29.3 nM and 9.9–41.7 nM, respectively. Notably, compound 4c was the most potent and selective CA IX (KI = 6.6 nM) and XII (KI = 9.9 nM) inhibitor with a significant selectivity ratio over cytosolic CA I and II isoforms in the range of 3.4–25.2. In addition, compounds having hydroxamic acid (15a-b) or carboxylic acid (16a-b) functionalities resulted in greater selectivity ratios for CA IX/XII over CAI/II in the range of 4.1–121.5 although with KI values in lower micromolar potency (KIs = 0.36–0.85 μM for CA IX/XII).
- ?al??kan, Burcu,Banoglu, Erden,Gür Maz, Tu??e,Nocentini, Alessio,Supuran, Claudiu T.,Uslu, Azize Gizem
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supporting information
(2020/01/08)
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- 1-CYANO-PYRROLIDINE DERIVATIVES AS DUB INHIBITORS
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The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R1a, R1b, R1c, R1d, R1e and R1f each independently represent hydrogen, optionally substituted C1-C6 alkyl or optionally substituted C3-C4 cycloalkyl, or R1b and R1c together form an optionally substituted C3-C6 cycloalkyl ring, or R1d and R1e together form an optionally substituted C3-C6 cycloalkyl ring; R2 represents hydrogen or optionally substituted C1-C6 alkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom.
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Paragraph 0810-0811
(2020/11/30)
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- SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE
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The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof. They are useful in preventing, managing, treating or lessening the severity of a protein kinase-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.
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Paragraph 000553
(2019/06/05)
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- BIS-BENZIMIDAZOLE COMPOUNDS AND METHODS OF USING SAME
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Provided herein are compounds and methods for modulating abnormal repeat expansions of gene sequences. More particularly, provided are inhibitors of RNA and the uses of such inhibitors in regulating nucleotide repeat expansions, e.g., to treat Myotonic Dystrophy Type 1 (DM1 ), Myotonic Dystrophy Type 2 (DM2), Fuchs dystrophy, Huntington Disease, Amyotrophic Lateral Sclerosis, or Frontotemporal Dementia.
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Paragraph 00500-00502
(2019/06/05)
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- Compound Shape Effects in Minor Groove Binding Affinity and Specificity for Mixed Sequence DNA
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AT specific heterocyclic cations that bind in the DNA duplex minor groove have had major successes as cell and nuclear stains and as therapeutic agents which can effectively enter human cells. Expanding the DNA sequence recognition capability of the minor
- Guo, Pu,Farahat, Abdelbasset A.,Paul, Ananya,Harika, Narinder K.,Boykin, David W.,Wilson, W. David
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supporting information
p. 14761 - 14769
(2018/11/02)
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- PYRAZOLO[1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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The invention provides substituted pyrazolo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidinyl carboxamide compounds described herein include 2-heterocyclyl-4-alkyl-pyrazolo[1,5-a]pyrirnidine-3-carboxarnide compounds and variants thereof.
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Paragraph 00742
(2017/11/06)
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- Benzimidazole derivative and preparation method therefor.
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The invention discloses a benzimidazole derivative and a preparation method therefor. The benzimidazole derivative is 1-methyl-2-phenyl-5-bromo-1(i)H(/i)-benzimidazole, and is an intermediate for preparing anticancer medicines and organic electroluminesce
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Paragraph 0023-0028
(2017/02/09)
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- SUBSTITUTED 2-AZA-BICYCLO[2.2.1]HEPTANE-3-CARBOXYLIC ACID (BENZYL-CYANO-METHYL)-AMIDES INHIBITORS OF CATHEPSIN C
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This invention relates to 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid (benzyl-cyano-methyl)- amides of formula (1) and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.
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Page/Page column 231
(2014/09/29)
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- SUBSTITUTED 2-AZA-BICYCLO[2.2.1]HEPTANE-3-CARBOXYLIC ACID (BENZYL-CYANO-METHYL)-AMIDES INHIBITORS OF CATHEPSIN C
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This invention relates to 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid(benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.
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Paragraph 0624; 0625
(2014/09/29)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 206-207
(2012/09/21)
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- INHIBITORS OF 11beta-HYDROXYSTEROID DEHYDROGENASE 1
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This invention relates to novel compounds of the Formula (I), (Ia1-10), (Ib1-10), (Ic1-10), (Id1-7), (Ie1-5) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.
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Page/Page column 26
(2012/05/07)
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- NITROGENATED HETEROCYCLIC RING DERIVATIVE AND ORGANIC ELECTROLUMINESCENT ELEMENT COMPRISING SAME
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A nitrogen-containing heterocyclic derivative represented by the following formula (1): wherein any "12-a" groups of R1 to R12 are independently a hydrogen atom, a fluorine atom, a substituted or unsubstituted aryl group having 6 to 30 ring carbon atoms or a substituted or unsubstituted heterocyclic group having 5 to 30 ring atoms; any "a" groups of R1 to R12 are independently a single bond which is bonded to L1; L1 is a single bond, a "b+1" valent substituted or unsubstituted hydrocarbon ring group having 6 to 30 ring carbon atoms or a "b+1" valent substituted or unsubstituted heterocyclic group having 5 to 30 ring atoms; HAr is a substituted or unsubstituted nitrogen-containing heterocyclic group; and "a" and "b" are independently an integer of 1 to 4, and at least one of "a" and "b" is 1. Also disclosed is a nitrogen-containing heterocyclic derivative represented by the following formula (21) or (31):
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Page/Page column 32
(2012/12/13)
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- Exploration of larger central ring linkers in furamidine analogues: Synthesis and evaluation of their DNA binding, antiparasitic and fluorescence properties
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The effects of replacing the central furan ring of furamidine with indole and benzimidazole on their DNA binding affinity, antiparasitic activity and fluorescence are reported. The bis-cyanophenylindoles required to make the corresponding amidines were prepared by sequential Stille and/or Suzuki coupling reactions. The bis-cyanophenylbenzimidazoles were obtained by coupling 4-cyanobenzaldehydes with the appropriate cyano substituted phenylenediamine. The bis-nitriles were converted to the diamidines by reaction with LiN[Si(CH3)3]2 or by Pinner methodology. Specifically, we have prepared new series of 2,6- and 2,5-diaryl indoles (6a,b, 12 and 17a-d) and the related benzimidazoles (24, 30 and 35). The new compounds bind in the DNA minor groove in DNA AT base pair sequences and eight of the ten new analogues exhibit ΔTm values comparable to or higher than that of furamidine. Six of ten of the new compounds exhibit lower IC 50 values against Trypanosoma brucei rhodesiense (T. b. r.) and eight of ten exhibit lower IC50 values against Plasmodium falciparum (P. f.) than furamidine. Four of the ten show greater efficacy than furamidine in the rigorous T. b. r. STIB900 mouse model for African trypanosomiasis. Generally, the fluorescence properties of the new analogues are similar to that of DAPI.
- Farahat, Abdelbasset A.,Paliakov, Ekaterina,Kumar, Arvind,Barghash, Alaa-Eldin M.,Goda, Fatma E.,Eisa, Hassan M.,Wenzler, Tanja,Brun, Reto,Liu, Yang,Wilson, W. David,Boykin, David W.
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scheme or table
p. 2156 - 2167
(2011/05/06)
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- ANTIBACTERIAL COMPOUNDS
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Disclosed are compounds of formula (I), which are of use in the treatment of bacterial diseases and infections, to compositions containing those compounds and to methods of treating bacterial diseases and infections using the compounds. In particular, the compounds are useful for the treatment of infection with, and diseases caused by, Clostridium difficile.
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Page/Page column 52
(2010/06/20)
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- The development of benzimidazoles as selective rho kinase inhibitors
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Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC50 10 nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA).
- Sessions, E. Hampton,Smolinski, Michael,Wang, Bo,Frackowiak, Bozena,Chowdhury, Sarwat,Yin, Yan,Chen, Yen Ting,Ruiz, Claudia,Lin, Li,Pocas, Jennifer,Schr?ter, Thomas,Cameron, Michael D.,LoGrasso, Philip,Feng, Yangbo,Bannister, Thomas D.
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scheme or table
p. 1939 - 1943
(2010/09/03)
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- COMPOUNDS AND COMPOSITIONS AS MICROSOMAL PROSTAGLANDIN E SYNTHASE-1 INHIBITORS
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Provided herein are compounds, and pharmaceutical compositions comprising such compounds, wherein the compounds are inhibitors of mPGES-1 activity. Also provided herein are methods of using such compounds and composition to treat or prevent diseases or di
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Page/Page column 108-109
(2010/11/17)
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- Fused bicyclic mTOR inhibitors
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Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.
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Page/Page column 68
(2008/06/13)
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- Highly chemoselective nitration of aromatic amines using the Ph3P/Br2/AgNO3 system
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The use of PPh3/Br2/AgNO3 provides a new reagent system for the novel and highly chemoselective nitration of aromatic amines under mild reaction conditions.
- Iranpoor, Nasser,Firouzabadi, Habib,Nowrouzi, Najmeh,Firouzabadi, Dena
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p. 6879 - 6881
(2007/10/03)
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- NITROGENOUS HETEROCYCLE DERIVATIVE AND ORGANIC ELECTROLUMINESCENT ELEMENT EMPLOYING THE SAME
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Provided is a material for an organic EL device realizing an organic EL device capable of having a high current efficiency even at a low voltage. Provided is a derivative of heterocyclic compound having a nitrogen atom represented by the following general formula (A-1) or (A-2). In the formulae, R 1a to R 5a each represent a substituent, Ar 1a to Ar 3a each represent a single bond or a divalent connecting group, and HAr represents a group represented by a general formula (A-3) or (A-4). R 6a to R 10a each represent a substituent.
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Page/Page column 44-45
(2008/06/13)
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- NITROGEN-CONTAINING HETEROCYCLE DERIVATIVE AND ORGANIC ELECTROLUMINESCENT ELEMENT USING THE SAME
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A novel derivative of heterocyclic compound having nitrogen atom with a structure made by bonding special groups to benzimidazole, a material for an organic electroluminescence (EL) device comprising the derivative of heterocyclic compound having nitrogen atom and an organic electroluminescence device comprising at least one organic compound layer containing a light emitting layer sandwiched between a pair of electrodes, wherein the device contains the derivative of heterocyclic compound having nitrogen atom. An organic EL device achieving elevation of luminance and of efficiency in light emission even under low driving voltage is obtainable by an employment of the derivative of heterocyclic compound having nitrogen atom for at least one layer composing organic compound layers of the EL device.
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Page/Page column 39
(2010/02/14)
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- CALCIUM RECEPTOR MODULATING ARYLALKYLAMINES
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The compounds of the invention are represented by the following general structure (I) or a pharmaceutically acceptable salt thereof, and compositions containing them, wherein the variables are defined herein, and their use to reduce or inhibit PTH secretion, including methods for reducing or inhibiting PTH secretion and methods for treatment or prophylaxis of diseases associated with bone disorders, such as osteoporosis, or associated with excessive secretion of PTH, such as hyperparathyroidism. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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- Efficient solution phase synthesis of 2-(N-acyl)-aminobenzimidazoles
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An efficient solution phase protocol for the synthesis of 2-(N-acyl)-aminobenzimidazoles is reported. The 2-(N-acyl)-aminobenzimidazole ring system was assembled using SNAr reactions, nitro group reduction, acylthiourea formation and cyclization with EDC. The acyl protected 2-aminobenzimidazole derivatives were obtained in high yield and purity without purification of intermediates or final products. This reaction sequence eliminates the use of highly toxic cyanogen bromide, a reagent commonly used to prepare the 2-aminobenzimidazole ring system.
- Seth, Punit P.,Robinson, Dale E.,Jefferson, Elizabeth A.,Swayze, Eric E.
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p. 7303 - 7306
(2007/10/03)
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- Antithrombotic quinoxazolines
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Quinoxazolines having antithrombotic activity. Exemplary of those disclosed are: 4-{[6-(N-carboxymethyl-quinolin-8-yl-sulphonylamino)-1-methyl-2-oxo-1,2-dihydroquinoxalin-3-yl]-methyl}-benzamidine, 4-{[6-(1-(N-cyclopentyl-carboxymethylcarbonylamino)-cyclo-propyl)-1-methyl-2-oxo-1,2-dihydroquinoxalin-3-yl]-methyl}-benzamidine, and 4-{[7-(N-carboxymethylaminocarbonyl-ethylamino)-4-methyl-quinolin-2-yl]-oxo}-benzamidine.
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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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