- Excited state tautomerization of azaindole
-
Fluorescent tryptophan analogs, like azatryptophan, offer an advantage for exploring protein and peptide structure and dynamics. The chromophoric moieties, azaindole, of the azatryptophan analogs are investigated for their potential as fluorescent probes. The photophysical properties of 4-azaindole (4AI) and 5-azaindole (5AI) and their tautomers are characterized through computational and experimental methods. Both 4AI and 5AI undergo excited state tautomerization in the presence of 1 M NaOH. The protonated forms of 4AI and 5AI have a fluorescence emission of 415 and 410 nm, respectively, while the tautomers of 4AI and 5AI have a fluorescent emission of 480 and 450 nm, respectively. Gas phase computations (B3LYP/6-31+G**) show that the N1H azaindole tautomer is lower in energy in the ground state by as much as 12.5 kcal mol-1, while the N″H azaindole tautomer is lower in energy in the excited state by as much as 18.1 kcal mol-1. Solvent effects on the tautomer energy differences were computed using the isodensity polarized continuum model (IPCM). The polarity of the solvent helps to reduce the energy difference between the tautomers in the ground state by as much as 5.8 kcal mol-1, but not enough to reverse the ground state tautomer preference. The Royal Society of Chemistry 2005.
- Cash, Michael T.,Schreiner, Peter R.,Phillips, Robert S.
-
-
Read Online
- Selective ortho methylation of nitroheteroaryls by vicarious nucleophilic substitution
-
(Chemical Equation Presented) An efficient and scalable three-step one-pot approach to 6-methyl-5-nitroisoquinoline (1) from inexpensive 5-nitroisoquinoline, utilizing the vicarious nucleophilic substitution (VNS) as a key step, is described. The optimized reaction conditions can be applied to a limited number of other aromatic and heteroaromatic nitro compounds. Attempts to understand the observed selectivity in the VNS step led to the discovery of two new reaction pathways under VNS conditions, one leading to an isoxazole and the other resulting in the formal cyclopropanation of an aromatic nitro compound.
- Achmatowicz, Michal,Thiel, Oliver R.,Gorins, Gilles,Goldstein, Corinne,Affouard, Caroline,Jensen, Randy,Larsen, Robert D.
-
-
Read Online
- Method for preparing nitro compound by using graphene to catalyze nitric oxide
-
The invention discloses a method for preparing a nitro compound by using graphene to catalyze nitric oxide. A graphene oxide carbon material is used for catalysis of a reaction of nitric oxide and a nitrification substrate such as an aromatic compound to prepare the nitro compound. The method is used for replacing a traditional nitric acid/sulfur acid method to prepare the nitro compound, so thatthe atom utilization rate of the reaction is increased, the energy is saved, and the emission is reduced; and the method has the characteristic of atom economy during industrial preparation of the nitro compound.
- -
-
Paragraph 0043; 0044
(2018/06/16)
-
- Discovery and bioactivity of 4-(2-arylpyrido[3′,2′:3,4] pyrrolo[1,2-f][1,2,4]triazin-4-yl) morpholine derivatives as novel PI3K inhibitors
-
PI3K is a promising therapeutic target for cancer. With PI-103 as the lead compound, we designed and synthesized 4-(2-arylpyrido[3′,2′:3,4] pyrrolo[1,2-f][1,2,4]triazin-4-yl)morpholine derivatives. 9, 10a, 10d, 10e had the IC50 against PI3Kα comparable with PI-103. All of the compounds showed selectivity over 15 tested protein kinases and anti-proliferative activity at micromolar concentration against several cancer cell lines.
- Wang, Jia,Wang, Xiang,Chen, Yanhong,Chen, Simeng,Chen, Guang,Tong, Linjiang,Meng, Linghua,Xie, Yuyuan,Ding, Jian,Yang, Chunhao
-
scheme or table
p. 339 - 342
(2012/03/11)
-
- Nitrosation of aryl and heteroaryltrifluoroborates with nitrosonium tetrafluoroborate
-
Organotrifluoroborates have emerged as an alternative to toxic and air- and moisture-sensitive organometallic species for the synthesis of functionalized aryl and heteroaryl compounds. It has been shown that the trifluoroborate moiety can be easily converted into a variety of different substituents in a late synthetic stage. In this paper, we disclose a mild, selective, and convenient method for the ipso-nitrosation of organotrifluoroborates using nitrosonium tetrafluoroborate (NOBF4). Aryl- and heteroaryltrifluoroborates were converted into the corresponding nitroso products in good to excellent yields. This method proved to be tolerant of a broad range of functional groups.
- Molander, Gary A.,Cavalcanti, Livia N.
-
experimental part
p. 4402 - 4413
(2012/06/18)
-
- Novel 3-azaindolyl-4-arylmaleimides exhibiting potent antiangiogenic efficacy, protein kinase inhibition, and antiproliferative activity
-
Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.
- Ganser, Christopher,Lauermann, Eva,Maderer, Annett,Stauder, Torsten,Kramb, Jan-Peter,Plutizki, Stanislav,Kindler, Thomas,Moehler, Markus,Dannhardt, Gerd
-
p. 9531 - 9540
(2013/01/16)
-
- Chemical development of the casein kinase i - Epsilon inhibitor: 3-(3-fluorophenyl)sulfanyl-1 H -pyrrolo[3,2- b pyridine-2-carboxylic acid amide
-
The development of a scalable process for 3-arylsulfanyl-1H-pyrrolo[3,2- bpyridine-2-carboxylic acid amides (1), potent casein kinase I inhibitors, is described. The rapid identification of suitable reaction conditions expedited the lab scale synthesis of drug substances for early toxicological evaluations. Further improvements were made to achieve a safe and cost-effective process to meet increasing demands for drug substances to support clinical studies. This paper describes the synthesis at multikilogram scale.
- Huang, Bao-Guo,Kubiak, Gregory,Shay, John J.,Pemberton, Clive,Peers, James,Hanna, Reda G.,Powers, Matthew R.,Gamboa, Juan A.,Gelormini, Ann M.,Yarabe, Hyacinthe,Rudisill, Duane E.
-
experimental part
p. 1040 - 1045
(2011/12/21)
-
- Facile one-pot direct arylation and alkylation of nitropyridine N -oxides with grignard reagents
-
Facile arylation and alkylation of nitropyridine N-oxides were developed through the reactions of Grignard reagents with nitropyridine N-oxides. For the same 4-nitropyridine N-oxide, arylation occurred at the 2- (or 6-) position, whereas alkylation occurred at the 3-position in an adjustably site-selective manner. The cooperative action of the two groups was discovered in the reactions of 3-nitropyridine N-oxides. This protocol can find wide applications in building various pyridine compounds as illustrated in total syntheses of Emoxipin and Caerulomycin A and E.
- Zhang, Fang,Duan, Xin-Fang
-
supporting information; scheme or table
p. 6102 - 6105
(2012/01/06)
-
- 3-(INDOLYL)- OR 3-(AZAINDOLYL)-4-ARYLMALEIMIDE COMPOUNDS AND THEIR USE IN TUMOR TREATMENT
-
The present invention relates to a compound of formula (I) wherein R, R and R are as defined in the description and the physiologically acceptable salts thereof as well as the physiologically acceptable solvates of the compounds of formula I and of the salts thereof. The compounds of formula I are suitable for treating tumors
- -
-
Page/Page column 34
(2011/07/07)
-
- 3-(indolyl)- or 3-(azaindolyl)-4-arylmaleimide derivatives for use in the treatment of colon and gastric adenocarcinoma
-
The present invention relates to the use of a compound of formula (I) wherein R1, and R3 are as defined in the description and R2 is a phenyl group which is substituted with 2 or 3 C1-G6 alkoxy groups, or a physiologically acceptable salt thereof, or a solvate of the compound of formula (I) or of the salt thereof, for treatment of colorectal or gastric adenocarcinoma.
- -
-
-
- HETEROCYCLIC COMPOUNDS AND THEIR USES
-
Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.
- -
-
Page/Page column 12
(2011/07/06)
-
- Site-selective azaindole arylation at the azine and azole rings via N-oxide activation
-
Subjection of N-methyl 6-and 7-azaindole N-oxides to a Pd(OAc) 2/DavePhos catalyst system enables regioselective direct arylation of the azine ring. Following deoxygenation, 7-azaindole substrates undergo an additional regioselective azole direct arylation event in good yield.
- Huestis, Malcolm P.,Fagnou, Keith
-
supporting information; scheme or table
p. 1357 - 1360
(2009/09/05)
-
- 3' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
-
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein Q, R1, R4, m and Ar are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
- -
-
Page/Page column 136-137
(2009/04/25)
-
- INHIBITORS OF FOCAL ADHESION KINASE
-
The invention provides inhibitors of focal adhesion kinase, an enzyme involved in the attachment of the cytoskeleton of a cell to an extracellular matrix, which has been implicated in processes such as cell migration, cell proliferation, and cell survival. The inhibitors are derivatives of a 5-substituted 2,4-diaminopyridine wherein the substituents are as defined herein. The invention also provides a method of using the inhibitors in treatment of cancer, and methods of preparation of the inhibitors by use of coupling reactions.
- -
-
Page/Page column 117
(2008/12/07)
-
- THIENO[2,3-D]PYRIMIDIN-4(3H)-ONE, ISOXAZOLO[5,4-D]PYRIMIDIN-4(5H)-ONE AND ISOTHIAZOLO[5,4-D]PYRIMIDIN-4(5H)-ONE DERIVATIVES AS CALCIUM RECEPTOR ANTAGONISTS
-
The present invention is directed to novel thieno[2,3-d]pyrimidin-4(3H)-one, isoxazolo[5,4-d]pyrimidin-4(5H)-one and isothiazolo[5,4-d]pyrimidin-4(5H)-one derivatives and pharmaceutically acceptable salts thereof of structural formula (I), wherein the variables R1, R2, R3, X and Z are as described herein. Also provided are pharmaceutical compositions comprising the compounds of formula I as well as methods of treatment employing compounds of formula I to treat a disease or disorder characterized by abnormal bone or mineral homeostasis such as hypoparathyroidism, osteoporosis, osteopenia, periodontal disease, Paget's disease, bone fracture, osteoarthritis, rheumatoid arthritis, and humoral hypercalcemia of malignancy.
- -
-
Page/Page column 52
(2009/03/07)
-
- Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists
-
We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.
- Giordanetto, Fabrizio,Karlsson, Olle,Lindberg, Jan,Larsson, Lars-Olof,Linusson, Anna,Evertsson, Emma,Morgan, David G.A.,Inghardt, Tord
-
p. 4232 - 4241
(2008/12/21)
-
- PYRROLO[2,3-C]PYRIDINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF
-
The present invention provides novel pyrrolo[2,3-c]pyridine derivatives or pharmaceutically acceptable salts thereof, processes for the preparation thereof, and compositions comprising the same. The pyrrolo[2,3-c]pyridine derivatives or pharmaceutically acceptable salts thereof of the present invention have excellent proton pump inhibition effects and possess the ability to attain a reversible proton pump inhibitory effect.
- -
-
Page/Page column 12
(2010/10/20)
-
- PYRROLO[2,3-c]PYRIDINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF
-
The present invention provides novel pyrrolo[2,3-c]pyridine derivatives or pharmaceutically acceptable salts thereof, processes for the preparation thereof, and compositions comprising the same. The pyrrolo[2,3-c]pyridine derivatives or pharmaceutically acceptable salts thereof of the present invention have excellent proton pump inhibition effects and possess the ability to attain a reversible proton pump inhibitory effect.
- -
-
Page/Page column 9
(2010/10/20)
-
- Substituted 1H-pyrrolo[3,2-b, 3,2-c, and 2,3-c]pyridine-2-carboxamides and related analogs as inhibitors of casein kinase lepsilon
-
The present invention discloses and claims compounds of formula (I) as inhibitors of human casein kinase IF, and methods of using said compounds of formula (I) for treating central nervous system diseases and disorders including mood disorders and sleep disorders. Pharmaceutical compositions comprising compounds of formula (I) and methods for the preparation of compounds of formula (I) are also disclosed and claimed.
- -
-
Page/Page column 13
(2008/06/13)
-
- PYRAZOLE COMPOUND AND MEDICINAL COMPOSITION CONTAINING THE SAME
-
The present invention provides a novel compound having an excellent JNK inhibitory effect. That is, it provides a compound represented by the following formula, a salt thereof or a hydrate of them. Wherein R1 designates -(CO)h-(NRa)j-(CRb=CRc)k-Ar (wherein Ra, Rb and Rc each independently designate a hydrogen atom, a halogen atom, hydroxyl group, an optionally substituted C1-6 alkyl group or the like; Cy designates a 5- or 6-membered heteroaryl; and V each independently designate the formula -L-X-Y (wherein L designates a single bond, an optionally substituted C1-6 alkylene group or the like; X designates a single bond or the formula -A- (wherein A designates NR2, O, CO, S, SO or SO2) and so on; and Y designates a hydrogen atom, a halogen atom, nitro group or the like).
- -
-
Page/Page column 134
(2008/06/13)
-
- PYRROLOPYRIDINE-2-CARBOXYLIC ACID AMIDE INHIBITORS OF GLYCOGEN PHOSHORYLASE
-
Compounds represented by Formula (I): or pharmaceutically acceptable salts thereof, are inhibitors of glycogen phosphorylase and are useful in the prophylactic or therapeutic treatment of diabetes, hyperglycemia, hypercholesterolemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis or tissue ischemia e.g. myocardial ischemia, and as cardioprotectants.
- -
-
-
- Synthesis of 2-aryl-1-hydroxyazaindoles and 2-arylazaindoles via oxidation of o-hydroxyaminostyrylpyridines
-
2-Aryl-1-hydroxyazaindoles (pyrrolopyridin-1-ols) are prepared via an oxidation/cyclization of o-hydroxyaminostyrylpyridines with DDQ. Reduction of the N-OH bond affords the corresponding 2-arylazaindoles (1H-pyrrolopyridines). The scope of the cyclization is explored via (i) the condensation of 4-methyl-3-nitropyridine with various aryl aldehydes to afford 2-aryl substituted 6-azaindoles and, (ii) the synthesis of 2-phenyl-4-, 5- and 7-azaindoles.
- Kuzmich, Daniel,Mulrooney, Carol
-
p. 1671 - 1678
(2007/10/03)
-
- B-alkyl suzuki-miyaura cross-coupling reactions with air-stable potassium alkyltrifluoroborates
-
The palladium-catalyzed cross-coupling reaction of substituted potassium alkyltrifluoroborates with aryl halides and aryl triflates proceeds readily with moderate to good yields. The potassium alkyltrifluoroborates 1, 2, and 3a-e were easily synthesized and obtained as air-stable crystalline solids that can be stored for long periods of time. All of the cross-couplings proceed under the same reaction conditions using PdCl2(dppf)·CH2cl2 as catalyst in THF-H2O in the presence of 3 equiv of Cs2CO3 as base.
- Molander, Gary A.,Yun, Chang-Soo,Ribagorda, Maria,Biolatto, Betina
-
p. 5534 - 5539
(2007/10/03)
-
- Practical methylation of aryl halides by Suzuki-Miyaura coupling
-
A number of aryl halides (X = Cl, Br, I) can be converted to the corresponding toluenes in an operationally simple manner using trimethylboroxine (TMB) as a partner for palladium-catalysed Suzuki-Miyaura coupling. (C) 2000 Elsevier Science Ltd.
- Gray,Andrews,Hook,Kitteringham,Voyle
-
p. 6237 - 6240
(2007/10/03)
-
- Process for the synthesis of ribonucleotide reductase inhibitors 3-AP and 3-AMP
-
The present invention relates to improved, efficient chemical syntheses of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (3-AMP).
- -
-
-
- Pyridylcarbamates, process and intermediates for their preparation, and their use
-
A pyridylcarbamate compound of the formula I STR1 wherein R' is hydrogen; opt. subst. alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkylcarbonyl and alkoxycarbonyl; R" is opt. subst. alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl; or is hydrogen when V is nitrogen; V is O, S or N; X is cyano; nitro; halogen; opt. subst. alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, or an opt. subst. bridge which is bonded to two adjacent C atoms of the pyridyl ring; n is 0, 1, 2 or 3; R is halogen; OH; SH; NH; CHO; CO2 H; CONH2 ; opt. subst. alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl or hetaryl, each being bonded directly or via O, S, N, CO2 or CONH; or together with X and the pyridyl ring to which they are bonded an opt. subst. bicyclus, its manufacture, and pesticidal and fungicidal compositions containing I.
- -
-
-
- Synthesis of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP)
-
Palladium-catalyzed cross-coupling of methylboronic acid with 2-chloro- 3-nitropyridine produced 2-methyl-3-nitropyridine 4 in one step in high yield. Oxidation of 4 with selenium dioxide gave aldehyde 5. Alternatively, condensation of 4 with DMFDMA followed by oxidation gave 5 in a two step higher yielding conversion. Subsequent direct coupling of 5 with thiosemicarbazide followed by reduction of the nitro group using stannous chloride or sodium sulfide provided 3-AP (3). Reduction with sodium hydrosulfite gave 3-HAP (8). Finally a route which avoids the reduction of a nitro function was devised. Thus direct coupling of styrene with 2-chloro-3- aminopyridine 9 under Heck reaction conditions gave 16 which was converted to 17, oxidized to the aldehyde 18 and converted to 3-AP (3) with in situ deblocking of the t-Boc functionality.
- Niu, Chuansheng,Li, Jun,Doyle, Terrence W.,Chen, Shu-Hui
-
p. 6311 - 6318
(2007/10/03)
-
- Reactions of thioamides with metal carboxylates in organic media
-
Reactions of thioamides with metal carboxylates in organic solvents are described. These processes enable the selective preparation of nitriles, imides or amides depending on the substitution pattern of the starting material. Mechanistic hypotheses supported by experimental evidences, including the unequivocal synthesis of bis(thioacetanilide)mercury(II) as a key reaction intermediate, are also proposed.
- Avalos, Martin,Babiano, Reyes,Cintas, Pedro,Duran, Carlos J.,Higes, Francisco J.,Jimenez, Jose L.,Lopez, Ignacio,Palacios, Juan C.
-
p. 14463 - 14480
(2007/10/03)
-
- Nitration of Aromatic and Heteroaromatic Compounds by Dinitrogen Pentaoxide
-
Nitration of benzene and monosubstituted benzenes in liquid SO2 by dinitrogen pentaoxide at - 11 deg C gave the corresponding nitroarenes with substitution patterns similar to those obtained by nitrations with HNO3-H2SO4.For acetophenone an o/m ratio of 0.94 was obtained.The yields were dependent on the substituents.With a 1:1 ratio of arene: N2O5 the yields varied from 73percent for toluene to 0.4percent for nitrobenzene as substrates.From competition experiments and the nitration of bibenzyl it was concluded that the reaction was faster than the macroscopic rate of mixing.The qualitative order of reactivity for PhX was X = OCH3>CH3>H>Cl>CH3CO>NO2.Nitration with N2O5 in liquid CO2 gave similar results.Nitration of pyrimidine, pyrrole, imidazole and indole with N2O5-SO2 gave no nitrated products.With thiophene, 2- (34percent) and 3-nitrothiophene (5percent) together with 2,4-(16percent) and 2,5-dinitrothiophene (8percent) were obtained.With pyridine, mono- and di-methylpyridines, quinoline, isoquinoline and 4-phenylpyridine nitration of the pyridine ring was obtained.The yields varied from ca. 70percent to 16percent, except for 3,5-, 2,5- and 2,6-dimethylpyridine for which only traces of nitro-dimethylpyridines were obtained.The reaction with the pyridines appears to be intramolecular both in the SO2 phase and in the water phase used for quenching the reaction.The reaction was proposed to proceed by a complex formed in liquid SO2:
- Bakke, Jan M.,Hegbom, Ingrid,Oevreeide, Elin,Aaby, Kjersti
-
p. 1001 - 1006
(2007/10/02)
-
- Synthesis of Pyrrolopyridines (Azaindoles)
-
Improved, convenient, and reliable routes for synthesis of 4-,5-,6-, and 7-azaindole, 7-methyl-4-azaindole, 7-methyl-6-azaindole, and the hithero unreported 7-amino-4-azaindole are described.The syntheses have been accomplished either by significant modifications to established procedures or by new methods with afford the compounds in improved yields.
- Mahadevan,Indumathy,Rasmussen, Malcolm
-
p. 359 - 367
(2007/10/02)
-
- A One-pot Synthesis of 3-Nitro- and 3,5-Dinitro-2-picolines
-
3-Nitro- and 3,5-dinitro-2-picoline were each prepared in a one-pot synthesis in high yield by treatment of the respective 2-chloro-3-nitro- and 2-chloro-3,5-dinitropyridines with diethyl sodiomalonate, followed by hydrolysis and decarboxylation with 50percent sulfuric acid.
- Liu, Mao-Chin,Lin, Tai-Shun,Sartorelli, Alan C.
-
p. 2965 - 2970
(2007/10/02)
-
- OXIDATIVE DEMETHYLATION OF SOME METHYLNITROPYRIDINE 1-OXIDES
-
3-Nitropyridine 1-oxide and 5-methyl-3-nitropyridine 1-oxide are produced readily by oxidative demethylation using SeO2 of 2-methyl- and 2,5-dimethyl-3-nitropyridine 1-oxides.
- Achremowicz, Lucjan
-
p. 2433 - 2434
(2007/10/02)
-
