bluuebunny/crossref_metadata_2025_split huggingface dataset:
4‐Hydroxy‐benzoic acid (4‐diethylamino‐2‐hydroxy‐benzylidene)hydrazide: DFT, antioxidant, spectroscopic and molecular docking studies with BSA
Authors: Sharma Vibha , Arora Ekta Kundra , Cardoza Savio 
Published: September 2015

AbstractThe Schiff base 4‐hydroxy‐benzoic acid (4‐diethylamino‐2‐hydroxy‐benzylidene) hydrazide (SL) was synthesized and characterized. Its antioxidant activity was evaluated using 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) free radical scavenging action. Being a potent antioxidant its binding ability to the transport protein bovine serum albumin (BSA) was studied using fluorescence quenching and circular dichroism (CD) studies. The binding distance has been calculated by fluorescence resonance energy transfer (FRET) to be 1.85 Å and the Stern–Volmer quenching constant has been calculated to be (3.23 ± 0.45) × 105 M–1. Quantum chemical analysis was carried out for the Schiff base using DFT with B3LYP and 6–311G** and related to the experimentally obtained results. For a deeper understanding of the mechanism of the interaction, the experimental data were complemented by protein–Schiff base docking calculations using Argus Lab. Copyright © 2015 John Wiley & Sons, Ltd.
Prognostic value of serum CYFRA21‐1 and CEA for non‐small‐cell lung cancer
Authors: Zhang Zhi‐Hui , Han Yun‐Wei , Liang Hui , Wang Le‐Min 
Published: September 2015

AbstractThe aim of the study was to assess the clinical prognostic value of serum cytokeratin 19 fragment (CYFRA21‐1) and carcinoembryonic antigen (CEA) for non‐small‐cell lung cancer (NSCLC) patients. Literatures related to effects of serum CYFRA21‐1 and CEA on the prognosis of lung cancer patients were retrieved from databases such as PubMed, Springer Link, Embase, Wanfang, and CNKI. Meta‐analysis was carried out using RevMan 5.1 software. Ten literatures involving 1990 NSCLC patients were selected in this study. Total survive estimation merging hazard ratio (HR) in all NSCLC patients with high‐level serum CYFRA21‐1 was 1.64 (95% CI 1.46–1.84, P < 0.001) and that in all NSCLC patients with high level serum CEA was 1.46 (95% CI 1.28–1.65, P < 0.001). Serum CYFRA21‐1 and CEA can be used as prognostic factors of NSCLC patients. Combinative detection of the two indices will be more reliable.
Prenatal diagnosis of a 46,XX male following noninvasive prenatal testing
Authors: Mansfield Nerida , Boogert Tom , McLennan Andrew 
Published: September 2015

Key Clinical messageCase report involving a normal female by NIPT with male external genitalia on routine fetal morphology assessment. QF‐PCR, CGH microarray, and FISH revealed an unbalanced translocation, involving the short arms of the X and Y chromosomes. This case demonstrates the possible limitations of correctly identifying sex chromosome abnormalities via NIPT.
Blue Electrogenerated Chemiluminescence from Water‐Soluble Iridium Complexes Containing Sulfonated Phenylpyridine or Tetraethylene Glycol Derivatized Triazolylpyridine Ligands
Authors: Kerr Emily , Doeven Egan H. , Barbante Gregory J. , Connell Timothy U. , Donnelly Paul S. , Wilson David J. D. , Ashton Trent D. , Pfeffer Frederick M. , Francis Paul S. 
Published: September 2015

AbstractIncorporating phenylpyridine‐ and triazolylpyridine‐based ligands decorated with methylsulfonate or tetraethylene glycol (TEG) groups, a series of iridium(III) complexes has been created for green and blue electrogenerated chemiluminescence under analytically useful aqueous conditions, with tri‐n‐propylamine as a coreactant. The relative electrochemiluminescence (ECL) intensities of the complexes were dependent on the sensitivity of the photodetector over the wavelength range and the pulse time of the applied electrochemical potential. In terms of the integrated area of corrected ECL spectra, with a pulse time of 0.5 s, the intensities of the IrIII complexes were between 18 and 102 % that of [Ru(bpy)3]2+ (bpy=2,2′‐bipyridine). However, when the intensities were measured with a typical bialkali photomultiplier tube, the signal of the most effective blue emitter, [Ir(df‐ppy)2(pt‐TEG)]+ (df‐ppy=2‐(2,4‐difluorophenyl)pyridine anion, pt‐TEG=1‐(2‐(2‐(2‐(2‐hydroxyethoxy)ethoxy)ethoxy)ethyl)‐4‐(2‐pyridyl)‐1,2,3‐triazole), was over 1200 % that of the orange–red emitter [Ru(bpy)3]2+. A combined experimental and theoretical investigation of the electrochemical and spectroscopic properties of the IrIII complexes indicated that the greater intensity from [Ir(df‐ppy)2(pt‐TEG)]+ relative to those of the other IrIII complexes resulted from a combination of many factors, rather than being significantly favored in one area.
Initiation Chemistries in Hydrocarbon (Aut)Oxidation
Authors: Sandhiya Lakshmanan , Zipse Hendrik 
Published: September 2015

AbstractFor the (aut)oxidation of toluene to benzyl hydroperoxide, benzyl alcohol, benzaldehyde, and benzoic acid, the thermochemical profiles for various radical‐generating reactions have been compared. A key intermediate in all of these reactions is benzyl hydroperoxide, the heat of formation of which has been estimated by using results from CBS‐QB3, G4, and G3B3 calculations. Homolytic OO bond cleavage in this hydroperoxide is strongly endothermic and thus unlikely to contribute significantly to initiation processes. In terms of reaction enthalpies the most favorable initiation process involves bimolecular reaction of benzyl hydroperoxide to yield hydroxy and benzyloxy radicals along with water and benzaldehyde. The reaction enthalpy and free energy of this process is significantly more favorable than those for the unimolecular dissociation of known radical initiators, such as dibenzoylperoxide or dibenzylhyponitrite.
Facile Synthesis of a Furan–Arylamine Hole‐Transporting Material for High‐Efficiency, Mesoscopic Perovskite Solar Cells
Authors: Krishna Anurag , Sabba Dharani , Yin Jun , Bruno Annalisa , Boix Pablo P. , Gao Yang , Dewi Herlina A. , Gurzadyan Gagik G. , Soci Cesare , Mhaisalkar Subodh G. , Grimsdale Andrew C. 
Published: September 2015

AbstractA novel hole‐transporting molecule (F101) based on a furan core has been synthesized by means of a short, high‐yielding route. When used as the hole‐transporting material (HTM) in mesoporous methylammonium lead halide perovskite solar cells (PSCs) it produced better device performance than the current state‐of‐the‐art HTM 2,2′,7,7′‐tetrakis‐(N,N‐di‐p‐methoxyphenylamine)‐9,9′‐spirobifluorene (spiro‐OMeTAD). The F101‐HTM‐based device exhibited both slightly higher Jsc (19.63 vs. 18.41 mA cm−2) and Voc (1.1 vs. 1.05 V) resulting in a marginally higher power conversion efficiency (PCE) (13.1 vs. 13 %). The steady‐state and time‐resolved photoluminescence show that F101 has significant charge extraction ability. The simple molecular structure, short synthesis route with high yield and better performance in devices makes F101 an excellent candidate for replacing the expensive spiro‐OMeTAD as HTM in PSCs.
ChemInform Abstract: Identification of Novel Cu, Ag, and Au Ternary Oxides from Global Structural Prediction.
Authors: Cerqueira Tiago F. T. , Lin Sun , Amsler Maximilian , Goedecker Stefan , Botti Silvana , Marques Miguel A. L. 
Published: September 2015

AbstractAb initio global structural prediction and specifically, the minima hopping method combined with high‐throughput calculations are used to explore the periodic table in search of novel oxide phases.
ChemInform Abstract: Influence of Valence Electron Concentration on Laves Phases: Structures and Phase Stability of Pseudo‐Binary MgZn2‐xPdx.
Authors: Thimmaiah Srinivasa , Miller Gordon J. 
Published: September 2015

AbstractThe series of title compounds (0.15 ≤ x ≤ 1.0) is synthesized from the elements (Ta tubes, Ar, 750 °C, 18 h, followed by annealing at 400 °C for 5 d, 90—95% yields) and characterized by single crystal XRD and TB‐LMTO‐ASA electronic structure calculations to analyze the effect of valence electron concentration on MgZn2.
ChemInform Abstract: Asymmetric Synthesis of Quaternary α‐Fluoro‐β‐keto‐amines via Detrifluoroacetylative Mannich Reactions.
Authors: Xie Chen , Dai Yanling , Mei Haibo , Han Jianlin , Soloshonok Vadim A. , Pan Yi 
Published: September 2015

AbstractA simple procedure is elaborated for the synthesis of α‐fluoro‐β‐keto‐amines (III) and (VI) by detrifluoroacetylative Mannich reaction of keto‐hydrates (I) and (V) with imines (II).
ChemInform Abstract: Remote Stereoinduction in the Organocuprate‐Mediated Allylic Alkylation of Allylic gem‐Dichlorides: Highly Diastereoselective Synthesis of (Z)‐Chloroalkene Dipeptide Isosteres.
Authors: Kobayakawa Takuya , Narumi Tetsuo , Tamamura Hirokazu 
Published: September 2015

AbstractThe allylic alkylation of isomeric dichlorides (I) and (IV) with organocuprates proceeds via 1,4‐asymmetric induction to afford corresponding (Z)‐chloroalkene dipeptide isosteres with high diastereoselectivity.
ChemInform Abstract: Formaldehyde N,N‐Dialkylhydrazones as Neutral Formyl Anion Equivalents in Iridium‐Catalyzed Asymmetric Allylic Substitution.
Authors: Breitler Simon , Carreira Erick M. 
Published: September 2015

AbstractFormaldehyde N,N‐dialkylhydrazones like (II) can be used as neutral C1‐nucleophiles in two different iridium‐catalyzed substitution reactions of allylic carbonates: either for kinetic resolution or, alternatively, for a stereospecific substitution.
ChemInform Abstract: Tuning Radical Reactivity Using Iodine in Oxidative C(sp3)—H/C(sp)—H Cross‐Coupling: An Easy Way Toward the Synthesis of Furans and Indolizines.
Authors: Tang Shan , Liu Kun , Long Yue , Qi Xiaotian , Lan Yu , Lei Aiwen 
Published: September 2015

AbstractIodine‐catalyzed oxidative cross‐coupling/cyclization for the synthesis of furans and indolizines is reported.
ChemInform Abstract: Selective Hydrogenolysis of Phenols and Phenyl Ethers to Arenes Through Direct C—O Cleavage over Ruthenium—Tungsten Bifunctional Catalysts.
Authors: Huang Yao‐Bing , Yan Long , Chen Meng‐Yuan , Guo Qing‐Xiang , Fu Yao 
Published: September 2015

AbstractThe recyclable bifunctional catalyst exhibits high catalytic activity for the hydrogenolysis of a wide range of phenols and aryl ethers, including dimeric lignin model compounds and simple phenols from lignin pyrolysis.
ChemInform Abstract: Copper‐Catalyzed γ‐Cyanation of Aza‐Baylis—Hillman Adducts Using Trimethylsilyl Cyanide.
Authors: Yadav Arvind K. , Yadav Lal Dhar S. 
Published: September 2015

AbstractThe cyanation of aza‐BH adducts with a conjugated double bond proceeds via an iminium ion.
ChemInform Abstract: A Transition‐Metal‐Free Heck‐Type Reaction Between Alkenes and Alkyl Iodides Enabled by Light in Water.
Authors: Liu Wenbo , Li Lu , Chen Zhengwang , Li Chao‐Jun 
Published: September 2015

AbstractUnder basic aqueous conditions and irradiation with UV light, various alkenes couple with non‐activated alkyl iodides.
ChemInform Abstract: Unprecedented One‐Pot Multicomponent Synthesis of Propargylamines Using Amberlyst A‐21 Supported CuI under Solvent‐Free Conditions.
Authors: Bosica Giovanna , Gabarretta John 
Published: September 2015

AbstractCuI supported on Amberlyst A‐21 is shown to be a highly efficient heterogeneous catalyst for the three‐component coupling of amines with various aliphatic or aromatic aldehydes and terminal alkynes leading to propargylamines.
ChemInform Abstract: CuBr2‐Catalyzed Enantioselective Routes to Highly Functionalized and Naturally Occurring Allenes.
Authors: Ma Shengming , et al.  
Published: September 2015

AbstractThe CuBr2‐catalyzed reaction of alkynes with aldehydes in the presence of (S)‐diphenylprolinol (PRO) allows an easy access to functionalized chiral allenes including the naturally occurring allene (VIIId).
ChemInform Abstract: Difluoromethylation and gem‐Difluorocyclopropenation with Difluorocarbene Generated by Decarboxylation.
Authors: Deng Xiao‐Yun , Lin Jin‐Hong , Zheng Jian , Xiao Ji‐Chang 
Published: September 2015

AbstractDifluoromethylene phosphobetaine (PDFA, II) is found to be an efficient difluorocarbene precursor in the difluoromethylation of the activated X—H bonds (X = N, O, S), aliphatic thiols (IV), and gem‐difluorocyclopropenation of alkynes.
ChemInform Abstract: (Chloromethyl)magnesium Chloride—Lithium Chloride: A Chemoselective Reagent for the Synthesis of Functionalized Aromatic Chlorohydrins.
Authors: Nishimura Rodolfo H. V. , Murie Valter E. , Soldi Rafael A. , Clososki Giuliano C. 
Published: September 2015

AbstractAryl and hetaryl aldehydes are efficiently transformed to the corresponding chlorohydrins.
ChemInform Abstract: N‐Methylation of Amines with Methanol at Room Temperature.
Authors: Tsarev Vasily N. , Morioka Yuna , Caner Joaquim , Wang Qing , Ushimaru Richiro , Kudo Akihiko , Naka Hiroshi , Saito Susumu 
Published: September 2015

AbstractThe title reaction undergoes under UV‐vis light irradiation using Ag/TiO2 as photocatalyst.
ChemInform Abstract: Stereoselective Reaction of 2‐Carboxythioesters‐1,3‐dithiane with Nitroalkenes: An Organocatalytic Strategy for the Asymmetric Addition of a Glyoxylate Anion Equivalent.
Authors: Massolo Elisabetta , Benaglia Maurizio , Genoni Andrea , Annunziata Rita , Celentano Giuseppe , Gaggero Nicoletta 
Published: September 2015

AbstractThe enantioselective organocatalyzed conjugate addition of a newly activated thioester acting as an acyl anion mimic is presented using a chiral bifunctional catalyst to control the stereochemistry.
ChemInform Abstract: A Silver(I)‐Catalyzed Intramolecular Ficini′s [2 + 2] Cycloaddition Employing Ynamides.
Authors: Wang Xiao‐Na , Ma Zhi‐Xiong , Deng Jun , Hsung Richard P. 
Published: September 2015

AbstractThe thermally driven [2 + 2] cycloaddition of substrates (I) and (IV) represents the first examples of an intramolecular Ficini reaction.
ChemInform Abstract: Falling‐Solid Flash Vacuum Pyrolysis: An Efficient Preparation of Arylacetylenes.
Authors: Wentrup Curt , Becker Juergen , Winter Hans‐Wilhelm 
Published: September 2015

AbstractStarting from 3‐methylisoxazolones and aryl aldehydes, 4‐arylmethylidene‐5(4H)‐isoxazolone or bis(isoxazolyl)methane derivatives are prepared.
ChemInform Abstract: Aerobic Oxidation of Cyclohexanones to Phenols and Aryl Ethers over Supported Pd Catalysts.
Authors: Zhang Zhenzhong , Hashiguchi Taishin , Ishida Tamao , Hamasaki Akiyuki , Honma Tetsuo , Ohashi Hironori , Yokoyama Takushi , Tokunaga Makoto 
Published: September 2015

AbstractA facile protocol for the direct oxidation of cyclohexanones to phenols using Pd on ZrO2 as catalyst and oxygen as terminal oxidant is developed.
ChemInform Abstract: Heterogeneously Catalyzed Direct C—H Thiolation of Heteroarenes.
Authors: Vasquez‐Cespedes Suhelen , Ferry Angelique , Candish Lisa , Glorius Frank 
Published: September 2015

AbstractAn operationally simple general methodology for the arylthiolation of heteroarenes including thiophene, benzothiophene, benzofuran, and indole derivatives is elaborated.
ChemInform Abstract: Rhodium(I)‐Catalyzed Regiospecific Dimerization of Aromatic Acids: Two Direct C—H Bond Activations in Water.
Authors: Gong Hang , Zeng Huiying , Zhou Feng , Li Chao‐Jun 
Published: September 2015

AbstractAn environmentally friendly, operationally simple and scalable synthesis of diaryl acids is elaborated.
ChemInform Abstract: Transition‐Metal‐Free, Ambient‐Pressure Carbonylative Cross‐Coupling Reactions of Aryl Halides with Potassium Aryltrifluoroborates.
Authors: Jin Fengli , Han Wei 
Published: September 2015

AbstractA series of biaryl ketones, e.g. fenofibrate (IVd), is prepared by an unprecedented carbonylative cross‐coupling of aryl iodides with aryltrifluoroborates (II).
ChemInform Abstract: Regioselective 1,2‐Addition of Organometallic Reagents to Unprotected Juglones.
Authors: Parker Kathlyn A. , Mindt Thomas L. 
Published: September 2015

AbstractJuglones (I) undergo regioselective 1,2‐addition with alkyllithium and alkyl Grignard reagents at the non‐hydrogen bonded carbonyl group to produce quinol adducts.
ChemInform Abstract: Palladium‐Catalyzed Asymmetric Reductive Heck Reaction of Aryl Halides.
Authors: Yue Guizhou , Lei Kaining , Hirao Hajime , Zhou Jianrong Steve 
Published: September 2015

AbstractAlkylammonium salts in glycol are used as hydrogen‐bond donors to promote halide dissociation under mild conditions.
ChemInform Abstract: An Efficient One Pot Three‐Component Nanocatalyzed Synthesis of Spiroheterocycles Using TiO2 Nanoparticles as a Heterogeneous Catalyst.
Authors: Tailor Yogesh Kumar , Khandelwal Sarita , Kumari Yogita , Awasthi Kamlendra , Kumar Mahendra 
Published: September 2015

AbstractStructurally diverse spiroheterocycles, spiroannulated with imidazothiazole and imidazothiadiazole, are obtained by an environmentally benign isocyanide based domino protocol involving the three‐component reaction of benzothiazole (I)/thiadiazole (IX), isocyanides (II), and isatins (IV)/cyclic carbonyl compounds (V)/(VII).
ChemInform Abstract: Visible‐Light‐Promoted Vinylation of Tetrahydrofuran with Alkynes Through Direct C—H Bond Functionalization.
Authors: Li Jing , Zhang Jing , Tan Haibo , Wang David Zhigang 
Published: September 2015

AbstractThe title reaction uses eosin Y as the catalyst, tBuOOH as the external oxidant, and a 45 W household lightbulb as the light source.
ChemInform Abstract: One‐Pot Green Synthesis of Novel Polysubstituted 1,2‐Dihydronaphtho[2,1‐b]furans.
Authors: Sadeghpour Mahdieh , Olyaei Abolfazl , Lotfiyan Jamshid , Rajabi Fatemeh 
Published: September 2015

AbstractA first one‐pot synthesis of the title compounds is presented.
ChemInform Abstract: Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters.
Authors: Engl Oliver D. , Fritz Sven P. , Wennemers Helma 
Published: September 2015

AbstractBoth enantiomers of oxindoles with adjacent tetrasubstituted cyclic and acyclic stereogenic centers can be obtained with excellent stereoselectivities by using either a cinchona alkaloid derivative (EDC) as catalyst or Takemoto′s catalyst in conjugate addition reactions of monothiomalonates (II) to isatin‐derived N‐Cbz ketimines.
ChemInform Abstract: A Heteropolyacid‐Based Ionic Liquid Immobilized onto Fibrous Nano‐Silica as an Efficient Catalyst for the Synthesis of Cyclic Carbonate from Carbon Dioxide and Epoxides.
Authors: Sadeghzadeh Seyed Mohsen 
Published: September 2015

AbstractThe fibrous nano‐silica supported heteropolyacid‐based ionic liquid is simply and cost‐effectively synthesized and exhibits high catalytic activity in the synthesis of cyclic carbonates (III) under mild and solvent‐free conditions.
ChemInform Abstract: Merger of Visible Light Induced Oxidation and Enantioselective Alkylation with a Chiral Iridium Catalyst.
Authors: Wang Chuanyong , Zheng Yu , Huo Haohua , Roese Philipp , Zhang Lilu , Harms Klaus , Hilt Gerhard , Meggers Eric 
Published: September 2015

AbstractChiral octahedral iridium(III) complex IBH having Δ‐configuration gives α‐diarylaminomethylated imidazolyl benzyl/alkyl ketones (III), (V) and (VII) in high yields with excellent enantioselectivities by photochemical reaction of corresponding imidazolyl derivatives with N,N‐diarylaminomethyltrimethylsilane (II).
ChemInform Abstract: Exploiting Amphiphilicity: Facile Metal Free Access to Thianthrenes and Related Sulfur Heterocycles.
Authors: Pawliczek Martin , Garve Lennart K. B. , Werz Daniel B. 
Published: September 2015

AbstractA series of thianthrenes is readily prepared by reaction of dithioloimines (I) with arynes derived from precursors (II).
ChemInform Abstract: One‐Pot Syntheses of 1H‐Pyrazolo[1,2‐B]phthalazine‐5,10‐diones and 2‐H‐Indazolo[2,1‐B]phthalazine‐1,6,11(13‐H)‐triones in Water by Auto Catalysis.
Authors: Reddy Y. Dathu , Kumar P. Praveen , Devi B. Rama , Reddy Venkata Ramana Ch. , Dubey P. K. 
Published: September 2015

AbstractThe title compounds are synthesized in an one‐pot, four component reaction of phthaloyl dichloride (I) , hydrazine hydrate, various aryl aldehydes (II) and malononitrile (III), ethyl cynoacetate (V) or dimedone (VII) in refluxing water.
ChemInform Abstract: Controlled Synthesis of 1,3,5‐Oxadiazin‐2‐ones and Oxazolones Through Regioselective Iodocyclization of Ynamides.
Authors: Huang Hai , Zhu Xiaolin , He Guangke , Liu Qi , Fan Junzhen , Zhu Hongjun 
Published: September 2015

AbstractThe title synthesis is controlled by the solvent.
ChemInform Abstract: Synthesis of 4‐Silaspiro[3.4]octa‐1,5‐diene Derivatives: Hybrid Spiro Compounds.
Authors: Khan Ezzat , Wrackmeyer Bernd , Kempe Rhett , Glatz Germund 
Published: September 2015

AbstractThe title compounds are obtained by combining consecutive intermolecular 1,2‐dihydroboration and intramolecular 1,1‐carboboration reactions starting from trialkynyl(vinyl)silanes and 9‐BBN.
ChemInform Abstract: Leishmania Cell Wall as a Potent Target for Antiparasitic Drugs. A Focus on the Glycoconjugates
Authors: Cabezas Yari , Legentil Laurent , Robert‐Gangneux Florence , Daligault Franck , Belaz Sorya , Nugier‐Chauvin Caroline , Tranchimand Sylvain , Tellier Charles , Gangneux Jean‐Pierre , Ferrieres Vincent 
Published: September 2015

AbstractReview: 115 refs.
Use of a Novel Sub‐2 µm Silica Hydride Vancomycin Stationary Phase in Nano‐Liquid Chromatography. II. Separation of Derivatized Amino Acid Enantiomers
Authors: Rocchi Silvia , Fanali Chiara , Fanali Salvatore 
Published: September 2015

AbstractA novel vancomycin silica hydride stationary phase was synthesized and the particles of 1.8 µm were packed into fused silica capillaries of 75 µm internal diameter (I.D.). The chiral stationary phase (CSP) was tested for the separation of some derivatized amino acid enantiomers by using nano‐liquid chromatography (nano‐LC). Some experimental parameters such as the type and the content of organic modifier, the pH, and the concentration of the buffer added to the mobile phase were modified and the effect on enantioselectivity, retention time, and enantioresolution factor was studied. The separation of selected dansyl amino acids (Dns‐AAs), e.g., Asp, Glu, Leu, and Phe in their enantiomers was initially achieved utilizing a mobile phase containing 85% (v/v) methanol (MeOH) and formate buffer measuring the enantioresolution factor and enantioselectivity in the range 1.74–4.17 and 1.39–1.59, respectively. Better results were obtained employing a more polar organic solvent as acetonitrile (ACN) in the mobile phase. Optimum results (Rs 1.41–6.09 and α 1.28–2.36) were obtained using a mobile phase containing formate buffer pH 2.5/water/MeOH/ACN 6:19:12.5:62.5 (v/v/v/v) in isocratic elution mode at flow rate of 130 nL/min. Chirality 27:767–772, 2015. © 2015 Wiley Periodicals, Inc.
Potent and Selective Human Neutrophil Elastase Inhibitors with Novel Equatorial Ring Topology: in vivo Efficacy of the Polar Pyrimidopyridazine BAY‐8040 in a Pulmonary Arterial Hypertension Rat Model
Authors: von Nussbaum Franz , Li Volkhart M. , Meibom Daniel , Anlauf Sonja , Bechem Martin , Delbeck Martina , Gerisch Michael , Harrenga Axel , Karthaus Dagmar , Lang Dieter , Lustig Klemens , Mittendorf Joachim , Schäfer Martina , Schäfer Stefan , Schamberger Jens 
Published: September 2015

AbstractHuman neutrophil elastase (HNE) is a key driver of inflammation in many cardiopulmonary and systemic inflammatory and autoimmune conditions. Overshooting high HNE activity is the consequence of a disrupted protease–antiprotease balance. Accordingly, there has been an intensive search for potent and selective HNE inhibitors with suitable pharmacokinetics that would allowing oral administration in patients. Based on the chemical probe BAY‐678 and the clinical candidate BAY 85‐8501 we explored further ring topologies along the equator of the parent pyrimidinone lead series. Novel ring systems were annulated in the east, yielding imidazolo‐, triazolo‐, and tetrazolopyrimidines in order to ensure additional inhibitor–HNE contacts beyond the S1 and the S2 pocket of HNE. The western annulation of pyridazines led to the polar pyrimidopyridazine BAY‐8040, which combines excellent potency and selectivity with a promising pharmacokinetic profile. In vivo efficacy with regard to decreasing cardiac remodeling and amelioration of cardiac function was shown in a monocrotaline‐induced rat model for pulmonary arterial hypertension. This demonstrated in vivo proof of concept in animals.