- Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs
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New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO2, NH2, OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine "cores" (3a,3b) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19. Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers.
- Klinkebiel, Arne,Beyer, Ole,Malawko, Barbara,Lüning, Ulrich
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Read Online
- Mechanosensitive fluorescent probes, changing color like lobsters during cooking: Cascade switching variations
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Fluorescent flipper probes have been introduced recently to image physical forces in biology. Their design is inspired by the combination of planarization and polarization that makes the color of astaxanthin, a carotenoid, turn blue in living lobsters or shrimps. Flipper probes are constructed around twisted dithienothiophene dimers. Upon planarization, donors and acceptors placed on both sides are coupled to generate push-pull systems that shift excitation maxima to the red, while the emission wavelength is mechanoinsensitive. To assure chemical stability, these donors and acceptors have to turn on only upon planarization. In living lobster, this is achieved most beautifully with non-covalent hydrogen bonds to and from the surrounding, planarizing protein. With flipper probes, the unorthodox chalcogen bonds prove best to produce turn-on donors and acceptors. The specific objective of this study was to explore different turn-on donors for the resulting chalcogen-bonding cascade switches. The focus is on substitution of the original triazoles with ethylenedioxythiophene (EDOT) and ortho-hydroxyphenyl (HOP) donors. Design, synthesis and evaluation of the respective flipper probes are described.
- García-Calvo, José,Kato, Takehiro,Matile, Stefan,Sakai, Naomi,Strakova, Karolina
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Read Online
- Structure-Based Optimization of Small-Molecule Inhibitors for the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction
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Structure-based optimization was conducted to improve the potency, selectivity, and cell-based activities of β-catenin/B-cell lymphoma 9 (BCL9) inhibitors based on the 4′-fluoro-N-phenyl-[1,1′-biphenyl]-3-carboxamide scaffold, which was designed to mimic the side chains of the hydrophobic α-helical hot spots at positions i, i + 3, and i + 7. Compound 29 was found to disrupt the β-catenin/BCL9 protein-protein interaction (PPI) with a Ki of 0.47 μM and >1900-fold selectivity for β-catenin/BCL9 over β-catenin/E-cadherin PPIs. The proposed binding mode of new inhibitors was consistent with the results of site-directed mutagenesis and structure-activity relationship studies. Cell-based studies indicated that 29 disrupted the β-catenin/BCL9 interaction without affecting the β-catenin/E-cadherin interaction, selectively suppressed transactivation of Wnt/β-catenin signaling, downregulated expression of Wnt target genes, and inhibited viability of Wnt/β-catenin-dependent cancer cells in dose-dependent manners. A comparison of the biochemical and cell-based assay results offered the directions for future inhibitor optimization.
- Zhang, Min,Wang, Zhen,Zhang, Yongqiang,Guo, Wenxing,Ji, Haitao
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Read Online
- Rhodium-Catalyzed Twofold Unsymmetrical C-H Alkenylation-Annulation/Thiolation Reaction to Access Thiobenzofurans
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A Rh(III)-catalyzed twofold unsymmetrical C-H alkenylation-annulation/thiolation reaction has been developed, enabling the straightforward and efficient synthesis of various thiobenzofurans in one step. This robust protocol proceeds with a broad substrate scope and good functional group tolerance under relatively mild reaction conditions.
- Lin, Jian,Hu, Liuyu,Chen, Chao,Feng, Huijin,Yu, Yang,Yang, Yaxi,Zhou, Bing
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supporting information
p. 1194 - 1198
(2021/02/20)
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- THERAPEUTIC AGENT FOR INFLAMMATORY DISEASES, AUTOIMMUNE DISEASES, FIBROTIC DISEASES, AND CANCER DISEASES
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A therapeutic agent for treating at least one disease selected from the group consisting of inflammatory diseases, autoimmune diseases, fibrotic diseases, and cancer diseases, comprising: at least one selected from the group consisting of a compound represented by the following general formula (1) and pharmacologically acceptable salts thereof as an active ingredient. [In the formula (1), R1 and R2 may be the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group et al.; R3 represents a hydrogen atom; R4 represents an optionally substituted 4- to 10-membered monocyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom, and a sulfur atom; X represents a group represented by the following formula: -CH2-, - CH2-CH2-, -CH2-CH2-CH2-, or -CH2-O-CH2-; and Z represents a hydrogen atom or a hydroxyl group.]
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Paragraph 0143; 0170
(2021/05/06)
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- The Suzuki–Miyaura Cross-Coupling as the Key Step in the Synthesis of 2-Aminobiphenyls and 2,2'-Diaminobiphenyls: Application in the Synthesis of Schiff Base Complexes of Zn
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2-Nitrophenylboronic acids serve as interesting starting materials for the construction of biphenyl- and terphenyl-based amines if subjected to the Suzuki–Miyaura reaction. Unfortunately, these boronic acids suffer from low reactivity in Suzuki reactions, alongside their low stability in the presence of Pd. Herein, a general method for the construction of 2-nitro-substituted bi- and terphenyls is presented, with special emphasis on the synthesis of 2-amino-2'-nitrobi- and terphenyls. Comparisons are made with other boronic acids that have some of the aforementioned issues. Finally, the application of the obtained 2-amino-2'-nitrobi- and terphenyls as starting materials for the synthesis of bi- and terphenyl based di- and triamines is encountered for, with emphasis on the use of these amines as precursors for Schiff base ligands. In addition, the synthesis of some Zn complexes of these ligands is presented.
- Hylland, Knut Tormodss?nn,?ien-?degaard, Sigurd,Tilset, Mats
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supporting information
p. 4208 - 4226
(2020/07/06)
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- INHIBITORS FOR THE Β-CATENIN/B-CELL LYMPHOMA 9 (BCL9) PROTEIN–PROTEIN INTERACTION
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Disclosed are inhibitors for the β-catenin/BCL9 interaction. The inhibitors are selective for β-catenin/BCL9 over β-catenin/cadherin interactions. Methods of using the disclosed compounds to treat cancer are also disclosed.
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Page/Page column 42; 43
(2019/07/19)
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- NOVEL COMPOUND AND PHARMACOLOGICALLY ACCEPTABLE SALT THEREOF
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A compound represented by the general formula (1) below or a pharmacologically acceptable salt thereof: [In the formula (1), R1 and R2 may be the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group et al.; R3 represents a hydrogen atom; R4 represents an optionally substituted 4- to 10-membered monocyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom, and a sulfur atom; X represents a group represented by the following formula: —CH2—, —CH2—CH2—, —CH2—CH2—CH2—, or —CH2—O—CH2—; and Z represents a hydrogen atom or a hydroxyl group.]
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Paragraph 1163-1165; 1210; 1211
(2019/11/05)
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- Structure-Based Approach to Identify 5-[4-Hydroxyphenyl]pyrrole-2-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators
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In an effort to find new and safer treatments for osteoporosis and frailty, we describe a novel series of selective androgen receptor modulators (SARMs). Using a structure-based approach, we identified compound 7, a potent AR (ARE EC50 = 0.34 nM) and selective (N/C interaction EC50 = 1206 nM) modulator. In vivo data, an AR LBD X-ray structure of 7, and further insights from modeling studies of ligand receptor interactions are also presented.
- Unwalla, Ray,Mousseau, James J.,Fadeyi, Olugbeminiyi O.,Choi, Chulho,Parris, Kevin,Hu, Baihua,Kenney, Thomas,Chippari, Susan,McNally, Christopher,Vishwanathan, Karthick,Kilbourne, Edward,Thompson, Catherine,Nagpal, Sunil,Wrobel, Jay,Yudt, Matthew,Morris, Carl A.,Powell, Dennis,Gilbert, Adam M.,Chekler, Eugene L. Piatnitski
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supporting information
p. 6451 - 6457
(2017/08/02)
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- A facile color-tuning strategy for constructing a library of Ir(III) complexes with fine-tuned phosphorescence from bluish green to red using a synergetic substituent effect of -OCH3 and -CN at only the C-ring of C∧N ligand
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By simply grafting a -CN group and/or a -OCH3 group onto the meta- and/or para-site of the C-ring, a series of Ir(iii) complexes bearing a similar molecular platform of bis(1,2-diphenyl-1H-benzimidazolato-N,C2′)iridium(iii)(acetylacetonate), but showing fine-tuned phosphorescence covering nearly the whole window of the visible spectrum with a wide color-tuning range of 109 nm was acquired. With the help of DFT calculations, it was revealed that if the C-related arene moiety of the C∧N ligand (C-ring) contributes substantially to both the HOMO and LUMO of an Ir(iii) complex, the concurrent introduction of an electron-donating -OCH3 and an electron-withdrawing -CN groups on the C-ring at the meta- and para-sites relative to the Ir atom may lead to a favorable synergetic substituent effect on the color-tuning direction. This may represent a facile yet effective molecular design strategy for Ir(iii) complexes with a desirous emission color. A bluish green organic light-emitting diode (OLED) based on one of the objective complexes displayed a maximum current efficiency of 62.1 cd A-1, an external quantum efficiency of 19.8%, and a brightness of 48-040 cd m-2, implying that high-performance red and blue OLED phosphors as well as libraries of Ir(iii) complexes bearing similar molecular platforms may be developed through this -OCH3 and -CN synergetic substitution strategy.
- Jiao, Yan,Li, Ming,Wang, Ning,Lu, Tao,Zhou, Liang,Huang, Yan,Lu, Zhiyun,Luo, Daibing,Pu, Xuemei
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supporting information
p. 4269 - 4277
(2016/06/01)
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- Discovery of novel bacterial RNA polymerase inhibitors: Pharmacophore-based virtual screening and hit optimization
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The bacterial RNA polymerase (RNAP) is a validated target for broad spectrum antibiotics. However, the efficiency of drugs is reduced by resistance. To discover novel RNAP inhibitors, a pharmacophore based on the alignment of described inhibitors was used for virtual screening. In an optimization process of hit compounds, novel derivatives with improved in vitro potency were discovered. Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between σ70 and the RNAP core enzyme. Besides of reducing RNA formation, the inhibitors were shown to interfere with bacterial lipid biosynthesis. The compounds were active against Gram-positive pathogens and revealed significantly lower resistance frequencies compared to clinically used rifampicin.
- Hinsberger, Stefan,Hüsecken, Kristina,Groh, Matthias,Negri, Matthias,Haupenthal, J?rg,Hartmann, Rolf W.
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supporting information
p. 8332 - 8338
(2013/12/04)
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- A reagentless thermal post-synthetic rearrangement of an allyloxy-tagged metal-organic framework
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Direct heating of a metal-organic framework provides a simple, controllable way of effecting a covalent post-synthetic modification. Herein we report that an allyloxy-tagged zinc metal-organic framework undergoes a thermally-promoted aromatic Claisen rear
- Burrows, Andrew D.,Hunter, Sally O.,Mahon, Mary F.,Richardson, Christopher
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supporting information
p. 990 - 992
(2013/02/25)
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- The P1 N-isopropyl motif bearing hydroxyethylene dipeptide isostere analogues of aliskiren are in vitro potent inhibitors of the human aspartyl protease renin
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Novel nonpeptide small molecule renin inhibitors bearing an N-isopropyl P1 motif were designed based on initial lead structures 1 and aliskiren (2). (P3-P1)-Benzamide derivatives such as 9a and 34, as well as the corresponding P1 basic tertiary amine derivatives 10 and 35 were found to display low nanomolar inhibition against human renin in vitro.
- Yamaguchi, Yasuchika,Menear, Keith,Cohen, Nissim-Claude,Mah, Robert,Cumin, Frédéric,Schnell, Christian,Wood, Jeanette M.,Maibaum, Jürgen
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scheme or table
p. 4863 - 4867
(2010/05/18)
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- Dual aromatase-steroid sulfatase inhibitors
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By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in'vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC 50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.
- Woo, L. W. Lawrence,Bubert, Christian,Sutcliffe, Oliver-B.,Smith, Andrew,Chander, Surinder K.,Mahon, Mary F.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
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p. 3540 - 3560
(2008/02/09)
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- NOVEL DUAL ACTION RECEPTORS ANTAGONISTS (DARA) AT THE AT1 AND ETA RECEPTORS
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The present invention relates to new compounds of the formula [Chemical formula should be inserted here. Please see paper copy] wherein R1, R2, R3, and R31 are as specified herein. The invention also relates to a method for preparation thereof, as well as combinations of the new compounds with previously known agents. The invention also relates to the use of the above-mentioned compounds and combinations for the preparation of a medicament for treating hypertension of different kinds, alleviating organ damage of different kinds, treating or preventing diabetic nephropathy, treating endothelin and angiotensin mediated disorders, and treating prostate cancer.
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Page/Page column 304
(2010/11/28)
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- 2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
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The present invention has its object to provide a 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented with the Formula (1) , or the pharmaceutically acceptable salt, which is effective as a therapeutic and prophylactic agent for diabetes, diabetic nephropathy, or glomerulosclerosis.
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- Pyrrolobenzodiazepine arylcarboxamides and derivatives thereof as follicle-stimulating hormone receptor antagonists
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This invention provides pyrrolobenzodiazepine arylcarboxamides selected from those of Formula (1), which act as follicle stimulating hormone receptor antagonists, as well as pharmaceutical compositions and methods of treatment
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Page/Page column 23
(2008/06/13)
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- Pyrrolobenzodiazepine pyridine carboxamides and derivatives as follicle-stimulating hormone receptor antagonists
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This invention provides pyrrolobenzodiazepine pyridine carboxamides selected from those of Formula (1), which act as follicle stimulating hormone receptor antagonists. The invention also provides pharmaceutical compositions and methods of treatment utilizing the compounds of Formulae (1) and (2).
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Page/Page column 24
(2010/11/25)
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- 2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
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A 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented by the generalformula (1): [Chemical formula 1] (1) or a pharmaceutically acceptable saltthereof. They are useful as a therapeutic/preventive agent for diabetes, diabeticnephropathy, or glomerulosclerosis.
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Page/Page column 62-63
(2010/11/30)
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- 3, 4-SUBSTITUTED PYRROLIDINE DERIVATIVES FOR THE TREATMENT OF HYPERTENSION
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The invention relates to the use of (3,4-di-, 3,3,4-tri, 3,4,4-tri- or 3,3,4,4-tetra-)substituted pyrrolidine compounds for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; compounds that are part of a subclass of these substituted pyrrolidine compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (= disorder) that depends on activity of renin; new compounds that are part of a subclass of these substituted pyrrolidine compounds; pharmaceutical formulations comprising said substituted pyrrolidine compounds, and/or a method of treatment comprising administering said substituted pyrrolidine compounds, a method for the manufacture especially of said new substituted pyrrolidine compounds, as well as novel intermediates, starting materials and/or partial steps for their synthesis. The substituted pyrrolidine compounds are of the formula (I), wherein R1, R2, R3, R4, R5 and T are defined as in the specification.
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Page/Page column 164
(2010/11/24)
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- Structure-based design, synthesis, and study of potent inhibitors of β-ketoacyl-acyl carrier protein synthase III as potential antimicrobial agents
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Fatty acid biosynthesis is essential for bacterial survival. Components of this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. FabH, β-ketoacyl-ACP synthase III, is a particularly attractiv
- Nie, Zhe,Perretta, Carin,Lu, Jia,Su, Ying,Margosiak, Stephen,Gajiwala, Ketan S.,Cortez, Joseph,Nikulin, Victor,Yager, Kraig M.,Appelt, Krzysztof,Chu, Shaosong
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p. 1596 - 1609
(2007/10/03)
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- SULFAMIC ACID ESTER COMPOUNDS USEFUL IN THE INHIBITION OF SEROID SULPHATASE ACTIVITY AND AROMATASE ACTIVITY
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There is provided a compound of Formula (III) or Formula (IV), wherein A is selected from H, OH, halogen and hydrocarbyl D, E and F are each independently of each other an optional linker group; P, Q and R are independently of each other a ring system, wherein R4 and R5 are independently selected from H, alkyl, cycloalkyl, alkenyl, acyl and aryl, or combinations thereof, or together represent alkylene, wherein the or each alkyl or cycloalkyl or alkenyl or optionally contain one or more hetero atoms or groups
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Page/Page column 66
(2010/02/14)
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- Structural requirements for factor Xa inhibition by 3-oxybenzamides with neutral P1 substituents: Combining X-ray crystallography, 3D-QSAR, and tailored scoring functions
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The design, synthesis, and structure-activity relationship of 3-oxybenzamides as potent inhibitors of the coagulation protease factor Xa are described on the basis of X-ray structures, privileged structure motifs, and SAR information. A total of six X-ray structures of fXa/inhibitor complexes led us to identify the major protein-ligand interactions. The binding mode is characterized by a lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1 pocket, while polar parts are accommodated in S4. This alignment in combination with docking allowed derivation of 3D-QSAR models and tailored scoring functions to rationalize biological affinity and provide guidelines for optimization. The resulting models showed good correlation coefficients and predictions of external test sets. Furthermore, they correspond to binding site topologies in terms of steric, electrostatic, and hydrophobic complementarity. Two approaches to derive tailored scoring functions combining binding site and ligand information led to predictive models with acceptable predictions of the external set. Good correlations to experimental affinities were obtained for both AFMoC (adaptation of fields for molecular comparison) and the novel TScore function. The SAR information from 3D-QSAR and tailored scoring functions agrees with all experimental data and provides guidelines and reasonable activity estimations for novel fXa inhibitors.
- Matter, Hans,Will, David W.,Nazaré, Marc,Schreuder, Herman,Laux, Volker,Wehner, Volkmar
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p. 3290 - 3312
(2007/10/03)
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- Antiinflammation agents
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Compounds, compositions and methods that are useful in the treatment of inflammatory, immunoregulatory, metabolic, infectious and cell proliferative diseases or conditions are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, metabolism, infection and cell proliferation. The subject compounds contain a fused heterobicyclic ring.
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Page/Page column 35
(2010/02/06)
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- BIPHENYL CARBOXYLIC AMIDE P38 KINASE INHIBITORS
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Compounds of formula (I) or pharmaceutically acceptable derivatives thereof, and their use as pharmaceuticals, particularly as p38 kinase inhibitors.
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Page 43; 46; 47
(2008/06/13)
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- New oxybenzamide derivatives useful for inhibiting factor Xa or VIIa
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The present invention relates to compounds comprising the following formula: R0—Q—X—Q′—W—U—V—G—M??(I) These compounds are useful as pharmacologically active compounds. They exhibit an antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders such as thromboembolic diseases or restenoses. These compounds are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can generally be used to treat, prevent, or cure conditions in which an undesired activity of factor Xa and/or factor VIIa is present, or where inhibition of factor Xa and/or factor VIIa is intended. The invention further relates to processes for the preparation of these compounds, methods of their use (e.g., as active ingredients in pharmaceuticals), and pharmaceutical preparations comprising them.
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- Inhibitors of factor Xa and factor VIIa
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The present invention relates to compounds of the formula I,R0-Q-X-Q'-W-U-V-G-M in which Q; X; Q', U, V, G and M have the meanings indicated in the claims; R0 is aryl or heteroaryl; and W is selected from aryl, heteroaryl, carbocyclic and heterocyclic groups. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa(FXa) and/or factor VIIa(FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.
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- SUBSTITUTED BIPHENYL ISOXAZOLE SULFONAMIDES
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Compounds of the formula STR1 inhibit the activity of endothelin. The symbols are defined as follows: R 1, R 2, R 3 and R 4 are each directly bonded to a ring carbon and are each independently(a) hydrogen;(b) alkyl, alkenyl, alkynyl, alkoxy,
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- Substituted biphenyl isoxazole sulfonamides
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Compounds of the formula STR1 inhibit the activity of endothelin. The symbols are defined as follows: R1, R2, R3 and R4 are each directly bonded to a ring carbon and are each independently (a) hydrogen; (b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z1, Z2 and Z3 ; (c) halo; (d) hydroxyl; (e) cyano; (f) nitro; (g) --C(O)H or --C(O)R5 ; (h) --CO2 H or --CO2 R5 ; (i) --Z4 --NR6 R7 ; (j) --Z4 --N(R10)--Z5 --NR8 R9 ; or (k) R3 and R4 together may also be alkylene or alkenylene, either of which may be substituted with Z1, Z2 and Z3, completing a 4- to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; and the remaining symbols are as defined in the specification.
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- SUBSTITUTED BIPHENYL ISOXAZOLE SULFONAMIDES
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Compounds of the formula STR1 inhibit the activity of endothelin. The symbols are defined as follows: R 1, R 2, R 3 and R 4 are each directly bonded to a ring carbon and are each independently(a) hydrogen;(b) alkyl, alkenyl, alkynyl, alkoxy,
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