- Optically Active Spiranes, XI: Syntheses of Optically Active Mono to Heptasubstituted 5-Methyl and Ethyl-2,2'-Spirobiindanes and Related Naphthalene Derivatives of Known Chirality and Enantiomeric Purity
-
Starting from optically active 5,5'-dimethyl, diethyl, and 5-ethyl-5'-methyl-2,2'-spirobiindane as well as from 5'-ethyl-spirobiindane-5-carboxylic ester of known enantiomeric purity and configuration 75 mono to polysubstituted 2,2'-spirobiindanes have been prepared.Amongst these are several compounds with rings anellated in the 6,7 (and 6',7') positions, especially a spirohydrocarbon 4x with orthogonal naphthalene units the circular dichroism of which is reported and discussed.Several mono and disubstituted 5-methyl and ethylindanes (1, 2) have been prepared as models for synthetic transformations in the spirobiindane series.From the molar rotations of symmetrically diacylated 5,5'-dimethyl and diethyl spirobiindanes (4a, 7b, 7c) empirical ligand parameters λ for acetyl and methoxycarbonyl were determined which gave much better results in the calculation of the rotations of appropriate spirobiindanes (with the "shortened polynomal Ansatz") than the λ-values deduced previously from 5,5'-disubstituted spirobiindanes.The significance of these results is briefly discussed. - Keywords: Chirality function; Circular dichroism; Ligand parameters; 5-Methyl and ethylindanes; 1H-NMR spectra
- Neudeck, Horst,Schloegl, Karl
-
-
Read Online
- Palladium-catalyzed external-CO-free reductive carbonylation of aryl sulfonates
-
Pd-catalyzed reductive carbonylation of aryl sulfonates using N-formylsaccharin as a carbon monoxide (CO) surrogate was developed. This external-CO-free carbonylation provides a safe and practical access to aldehydes from phenol derivatives. The reaction has a broad substrate scope, rendering it an attractive method for synthesizing aldehydes.
- Konishi, Hideyuki,Kumon, Minoru,Yamaguchi, Miyuki,Manabe, Kei
-
-
- Computer-Assisted Discovery and Structural Optimization of a Novel Retinoid X Receptor Agonist Chemotype
-
As universal heterodimer partners of many nuclear receptors, the retinoid X receptors (RXRs) constitute key transcription factors. They regulate cell proliferation, differentiation, inflammation, and metabolic homeostasis and have recently been proposed as potential drug targets for neurodegenerative and inflammatory diseases. Owing to the hydrophobic nature of RXR ligand binding sites, available synthetic RXR ligands are lipophilic, and their structural diversity is limited. Here, we disclose the computer-assisted discovery of a novel RXR agonist chemotype and its systematic optimization toward potent RXR modulators. We have developed a nanomolar RXR agonist with high selectivity among nuclear receptors and superior physicochemical properties compared to classical rexinoids that appears suitable for in vivo applications and as lead for future RXR-targeting medicinal chemistry.
- Heitel, Pascal,Gellrich, Leonie,Kalinowsky, Lena,Heering, Jan,Kaiser, Astrid,Ohrndorf, Julia,Proschak, Ewgenij,Merk, Daniel
-
supporting information
p. 203 - 208
(2019/01/25)
-
- BI-CYCLO ALDEHYDE AS PERFUMING INGREDIENT
-
The present invention relates to the field of perfumery and concerns some bi-cyclo derivative of formula (I), wherein R1 represents a hydrogen atom or a C1-2 alkyl group; R2 represents a hydrogen atom or a methyl group; and A represents a group of formula C3-5 alkanediyl group; at least one of said R1 or R2 represents a group containing at least one carbon atom; and said compound being in the form of a E or Z isomer or of a mixture thereof. Said compounds are valuable perfuming ingredients capable of imparting lily of the valley and citrus notes.
- -
-
Page/Page column 8-9
(2015/01/16)
-
- Structure activity relationships of αv integrin antagonists for pulmonary fibrosis by variation in aryl substituents
-
Antagonism of αvβ6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an αvβ3 antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved αvβ6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan αv antagonists having ca. 100 nM potency against αvβ3, αvβ5, αvβ6, and αvβ8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for αvβ3 and αvβ5.
- Adams, James,Anderson, Edward C.,Blackham, Emma E.,Chiu, Yin Wa Ryan,Clarke, Thomas,Eccles, Natasha,Gill, Luke A.,Haye, Joshua J.,Haywood, Harvey T.,Hoenig, Christian R.,Kausas, Marius,Le, Joelle,Russell, Hannah L.,Smedley, Christopher,Tipping, William J.,Tongue, Tom,Wood, Charlotte C.,Yeung, Jason,Rowedder, James E.,Fray, M. Jonathan,McInally, Thomas,Macdonald, Simon J. F.
-
p. 1207 - 1212
(2015/04/27)
-
- NOVEL PROTEIN TYROSINE PHOSPHATASE - IB INHIBITORS
-
The present invention relates to the novel compounds of the general formula (I), wherein the symbols are same as described in specification, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, to process and intermediates for the preparation of the above said compounds, having the utility of these compounds in medicine and to methods for their therapeutic use, and their use in the treatment of metabolic disorders.
- -
-
Page/Page column 59
(2009/10/22)
-
- Synthesis of aromatic aldehydes by organocatalytic [4+2] and [3+3] cycloaddition of α,β-unsaturated aldehydes
-
Organocatalytic inter- and intramolecular [4+2] and [3+3] cycloadditions of α,β-unsaturated aldehydes to give polysubstituted aromatic aldehydes are described. High periselectivity for the cycloadditions, with catalyst effects exerted by l-proline and pyrrolidine-HOAc, as well as cocatalyst, additive effects, has been observed.
- Hong, Bor-Cherng,Tseng, Hsing-Chang,Chen, Shang-Hung
-
p. 2840 - 2850
(2007/10/03)
-
- AMIDES AND METHOD FOR PLANT DISEASE CONTROL WITH THE SAME
-
N-(α-cyanobenzyl)amide compounds represented by the formula (1): wherein R1 represents a hydrogen atom; a halogen atom; a C1-C6 alkyl group optionally substituted with a halogen atom or the like; or the like, R2 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group or the like, R3 represents a hydrogen atom or the like, R4 represents a C1-C4 alkyl group, a C3-C4 alkenyl group or the like, R5 represents a C1-C4 alkyl group, a C3-C4 alkenyl group, or the like, R6 represents a hydrogen atom or the like, R7 represents a hydrogen atom or the like, R8 represents a hydrogen atom or the like, R9 represents a hydrogen atom or the like, R10 represents a hydrogen atom or the like, R11 represents a hydrogen atom or the like, and R12 represents a hydrogen atom or the like, have excellent control activities against plant diseases.
- -
-
Page/Page column 78-79
(2010/11/08)
-
- AMIDE COMPOUND AND METHOD OF CONTROLLING PLANT DISEASE WITH THE SAME
-
A amid compound of the formula (1): wherein, in the formula, R51 represents a halogen atom, a C1-C6 alkyl group and the like; R52 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group and the like; R53 represents a halogen atom and the like; R56 represents a halogen atom and the like; R57 represents a hydrogen atom and the like; R58 and R59 independently represent a hydrogen atom, a C1-C3 alkyl group and the like; R60 represents a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C4 alkenyl group, or a C3-C6 alkynyl group; R61 represents a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C4 alkenyl group or a C3-C6 alkynyl group or a C2-C4 cyanoalkyl group; R62, R63 and R64 represent a hydrogen atom, a halogen atom and the like; X represents a oxygen atom or a sulfur atom; has an excellent activity against plant diseases.
- -
-
Page/Page column 102
(2010/02/14)
-
- Fungicidal Composition
-
A fungicidal composition comprising: an amide compound represented by formula (1) and dimethomorph as active ingredients, and a method for controlling plant diseases applying effective amount of an amide compound represented by formula (1) and dimethomorph to plant(s) or soil where plant(s) are growing.
- -
-
Page/Page column 17
(2010/02/15)
-
- Two classes of p38α MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes
-
Two new classes of diphenylether inhibitors of p38α MAP kinase are described. Both chemical classes are based on a common diphenylether core that is identified by simulated fragment annealing as one of the most favored chemotypes within a prominent hydrophobic pocket of the p38α ATP-binding site. In the fully elaborated molecules, the diphenylether moiety acts as an anchor occupying the deep pocket, while polar extensions make specific interactions with either the adenine binding site or the phosphate binding site of ATP. The synthesis, crystallographic analysis, and biological activity of these p38α inhibitors are discussed.
- Michelotti, Enrique L.,Moffett, Kristofer K.,Nguyen, Duyan,Kelly, Martha J.,Shetty, Rupa,Chai, Xiaomei,Northrop, Katrina,Namboodiri, Variketta,Campbell, Brandon,Flynn, Gary A.,Fujimoto, Ted,Hollinger, Frank P.,Bukhtiyarova, Marina,Springman, Eric B.,Karpusas, Michael
-
p. 5274 - 5279
(2007/10/03)
-
- Pyrimidinylpyrroloquinolones as highly potent and selective PDE5 inhibitors for treatment of erectile dysfunction
-
A series of N-pyrimidinylpyrroloquinolones were discovered as extremely potent and selective PDE5 inhibitors. Representative compounds demonstrated in vivo efficacy in dog erectile dysfunction models and are orally bioavailable.
- Sui, Zhihua,Guan, Jihua,Macielag, Mark J.,Jiang, Weiqin,Zhang, Suying,Qiu, Yuhong,Kraft, Patricia,Bhattacharjee, Sheela,John, T. Matthew,Haynes-Johnson, Donna,Clancy, Joanna
-
p. 4094 - 4096
(2007/10/03)
-
- Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists
-
The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported. As part of our own endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N- dibutylacetamido)-4-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3- carboxylic acid (A-127722). This is a potent antagonist, binding to the ET(A) and ET(B) receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and also contains the aforementioned benzodioxole. While this compound was seemingly optimized at its N-terminus, no effort had been directed toward understanding the contributions to binding affinity or receptor subtype selectivity conferred by the benzodioxole. Substitution by 1- or 2-naphthyl yielded weak antagonists. Oxygenated benzenes, such as p- anisyl, were potent compounds with IC50s in the low-nanomolar range. Simple deletion of either of the two oxygen atoms (dihydrobenzofurans) yielded extremely potent agents, possessing subnanomolar affinity for the ET(A) receptor. Additionally, the compounds showed enhanced selectivity, binding to the ET(B) receptor subtype in the micromolar range. This paper describes the development of this novel class of compounds.
- Tasker, Andrew S.,Sorensen, Bryan K.,Jae, Hwan-Soo,Winn, Martin,Von Geldern, Thomas W.,Dixon, Douglas B.,Chiou, William J.,Dayton, Brian D.,Calzadila, Samuel,Hernandez, Lisa,Marsh, Kennan C.,WuWong, J. Ruth,Opgenorth, Terry J.
-
p. 322 - 330
(2007/10/03)
-
- Synthesis and Pharmacological Examination of Benzofuran, Indan, and Tetralin Analogues of 3,4-(Methylenedioxy)amphetamine
-
Benzofuran, indan and tetrahydronaphthalene analogs of 3,4-(methylenedioxy)amphetamine (MDA) were prepared in order to examine the role of the dioxole ring oxygen atoms of MDA in interacting with the serotonin and catecholamine uptake carriers.The series of compounds was evaluated for discriminative stimulus effects in rats trained to discriminate saline from the training drugs (S)-(+)-MBDB (1c), MMAI (3), and (S)-(+)-amphetamine and for the ability to inhibit the uptake of 3H>serotonin, 3H>dopamine, and 3H>norepinephrine into crude synaptosome preparations.Behaviorally, the benzofuran and indan analogs 4-6 produced similar discriminative cues, whereas the tetralin derivative 7 did not fully substitute for the training drugs.The results in the in vitro pharmacology studies indicate that selectivity for 5-HT versus catecholamine uptake carriers may be modulated by the position and orientation of ring oxygen atoms.However, the nonoxygenated isostere 6 possessed high potency at all uptake sites examined.Enlargement of the saturated ring by one methylene unit to give the tetralin derivative resulted in a large (3-4-fold) reduction in activity at catecholamine sites.
- Monte, Aaron P.,Marona-Lewicka, Danuta,Cozzi, Nicholas V.,Nichols, David E.
-
p. 3700 - 3706
(2007/10/02)
-
- Formylation of Aromatic Compounds with CO in HSO3F-SbF5 under Atmospheric Pressure
-
The formylation of aromatic compounds such as benzene, toluene, xylenes, mesitylene, indan, tetralin, fluorobenzene, chlorobenzene, and bromobenzene was carried out in HSO3F-SbF5 under atmospheric CO pressure at 0 deg C.In HSO3F-SbF5, both formylation and sulfonation took place to give formyl and sulfonyl compounds.In the case of alkylbenzenes, including toluene, xylenes, mesitylene, and tetralin, formylalkylbenzenesulfonyl fluorides, new compounds, were obtained by a one-pot reaction as well as alkylbenzaldehydes, alkylbenzenesulfonyl fluorides, and bis(alkylphenyl) sulfones.The direct introduction of a formyl and sulfonyl group was achieved in alkylbenzenes.The reaction path of the new compounds is a two-step reaction comprised of formylation as the first step and sulfonation as the second step.The product composition was strongly dependent on the acid strength of the HSO3F-SbF5 systems.The formyl compounds became predominant with increasing acidity of the HSO3F-SbF5 system.On the other hand, only sulfonyl compounds were produced when the acidity of the HSO3F-SbF5 system was low.
- Tanaka, Mutsuo,Iyoda, Jun,Souma, Yoshie
-
p. 2677 - 2680
(2007/10/02)
-
- Benzannulation of Cyclopentanone, Cyclohexanone and Cycloheptanone: A Short Synthesis of Indane-5-carboxaldehyde, a Monoterpenoid Constituent of Ammomum medium
-
The Vilsmeier reaction on the homoallyl alcohols (1a-c), derived from cyclopentanone, cyclohexanone and cycloheptanone respectively, leads to a mixture of monocarboxaldehydes (2a-c) and dicarboxaldehydes (3a-c) which have been readily separated and characterized.The Vilsmeier route incidentally provides a short synthesis of indane-5-carboxaldehyde (2a), a terpenoid constituent of a medicinal plant.
- Rao, M. Suresh Chander,Rao, G. S. Krishna
-
p. 660 - 661
(2007/10/02)
-
- Aromatic Spiranes, XIV: Syntheses of 2,2'-Spirobi-(s-hydrindacene) and its precursors
-
The title compound 35 was prepared by catalytic reduction of the diones 29a and 11a. 29a was synthesized by systematic anellation of fivemembered rings to the positions 5,6 and 5',6', resp., of 2,2'-spirobiindane.The preparation of 11a was achieved by Friedel-Crafts cyclisation of bis-(5-indanylmethyl)-malonic acid. s-Hydrindacene-1-one 5a was prepared as a precursor for the synthesis of 11a (see forthcoming publication) and its derivates as models for corresponding anellation and substitution reactions. - Keywords: s-Hydrindacene-1-one and derivates; Mono- and bisanellation; 2,2'-Spirobiindane; 1H-nmr spectra
- Neudeck, Horst K.
-
p. 627 - 658
(2007/10/02)
-