- Cobalt-Catalyzed Desymmetric Isomerization of Exocyclic Olefins
-
Chiral cyclic olefins, 1-methylcyclohexenes, are versatile building blocks for the synthesis of pharmaceuticals and natural products. Despite the prevalence of these structural motifs, the development of efficient synthetic methods remains an unmet challenge. Herein we report a novel desymmetric isomerization of exocyclic olefins using a series of newly designed chiral cobalt catalysts, which enables a straightforward construction of chiral 1-methylcyclohexenes with diversified functionalities. The synthetic utility of this methodology is highlighted by a concise and enantioselective synthesis of a natural product, β-bisabolene. The versatility of the reaction products is further demonstrated by multifarious derivatizations.
- Lan, Yu,Liu, Qiang,Liu, Shihan,Liu, Xufang,Rong, Xianle
-
supporting information
p. 20633 - 20639
(2021/12/17)
-
- Synthesis and structure activity relationships of cyanopyridone based anti-tuberculosis agents
-
Mycobacterium tuberculosis, the causative agent of tuberculosis, relies on thymidylate kinase (MtbTMPK) for the synthesis of thymidine triphosphates and thus also DNA synthesis. Therefore, this enzyme constitutes a potential Achilles heel of the pathogen. Based on a previously reported MtbTMPK 6-aryl-substituted pyridone inhibitor and guided by two co-crystal structures of MtbTMPK with pyridone- and thymine-based inhibitors, we report the synthesis of a series of aryl-shifted cyanopyridone analogues. These compounds generally lacked significant MtbTMPK inhibitory potency, but some analogues did exhibit promising antitubercular activity. Analogue 11i demonstrated a 10-fold increased antitubercular activity (MIC H37Rv, 1.2 μM) compared to literature compound 5. Many analogues with whole-cell antimycobacterial activity were devoid of significant cytotoxicity.
- Boshoff, Helena I. M.,Caljon, Guy,Forbes, He Eun,Hulpia, Fabian,Jian, Yanlin,Munier-Lehmann, Héle?ne,Risseeuw, Martijn D. P.,Van Calenbergh, Serge
-
-
- Palladium-catalyzed intermolecular C-H silylation initiated by aminopalladation
-
A Pd(ii)-catalyzed intermolecular C-H silylation reaction initiated by aminopalladation has been developed. The C-H bonds were activated by an alkyl Pd(ii) species generated through aminopalladation and then disilylated with hexamethyldisilane to form disilylated indolines as the final products. The reaction provides a new method for the introduction of silyl groups into complex organic molecules.
- Ji, Xiaoming,Wei, Feng,Wan, Bin,Cheng, Cang,Zhang, Yanghui
-
supporting information
p. 7801 - 7804
(2020/07/27)
-
- BIARYL DERIVATIVE AND MEDICINE CONTAINING SAME
-
Provided is a compound showing excellent antifungal activity against Trichophyton fungus, which is a major causative microorganism of superficial mycosis, and high effectiveness on diseases caused by Trichophyton fungi. A biaryl derivative represented by the formula (I) or a salt thereof: wherein ring A is an optionally substituted phenyl, or an optionally substituted 5- or 6-membered ring heteroaryl (ring A may be further condensed to form an optionally substituted fused ring); Q is CH2, C=O, NH, O, S or the like; X1, X2 and X3 are CR1 or N; Y is CH or N; Z is CR2b or N; R2a and R2b are each a hydrogen atom, a halogen atom, an optionally substituted C1-C6 alkyl group, a C1-C6 haloalkyl group or the like; R2a and R2b may form, together with carbon atoms bonded thereto, an optionally substituted carbocycle, or an optionally substituted heterocycle.
- -
-
Paragraph 0655; 0656
(2018/08/07)
-
- PHARMACEUTICALS COMPRISING BIARYL DERIVATIVES OR SALTS THEREOF
-
PROBLEM TO BE SOLVED: To provide compounds with excellent antimycotic activity against Trichophyton. SOLUTION: The invention provides pharmaceuticals comprising biaryl derivatives represented by general formula (I) or salts thereof, where ring A is optionally substituted phenyl or the like; Q is CH2 or the like; X1, X2 and X3 are CR1 or the like; and Y is CH or N. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
- -
-
Paragraph 0618; 0619; 0620
(2018/10/24)
-
- Discovery of novel S1P2 antagonists, part 3: Improving the oral bioavailability of a series of 1,3-bis(aryloxy)benzene derivatives
-
The structure of the S1P2 antagonist 1 has been modified with the aim of improving its oral bioavailability. The chemical modification of the alkyl chain and carboxylic acid moieties of 1 led to significant improvements in the oral exposure of compounds belonging to this series. The optimization of the ring size of the urea portion of these molecules also led to remarkable improvements in the oral exposure. Based on these changes, the pyrrolidine derivative 16 was identified as a suitable candidate compound and showed excellent pharmacokinetic profiles in rat and dog, while maintaining high levels of potency and selective antagonistic activity toward S1P2.
- Kusumi, Kensuke,Shinozaki, Koji,Yamaura, Yoshiyuki,Hashimoto, Ai,Kurata, Haruto,Naganawa, Atsushi,Otsuki, Kazuhiro,Matsushita, Takeshi,Sekiguchi, Tetsuya,Kakuuchi, Akito,Yamamoto, Hiroshi,Seko, Takuya
-
p. 1209 - 1213
(2016/02/23)
-
- Beyond the affinity for protein kinase C: Exploring 2-phenyl-3-hydroxypropyl pivalate analogues as C1 domain-targeting ligands
-
Over the past fifteen years, we reported the design and synthesis of different series of compounds targeting the C1 domain of protein kinase C (PKC) that were based on various templates. Out of the pivalate templates, 2-[4-(benzyloxy)phenyl]-3-hydroxypropyl pivalate (compound 1) emerged as the most potent and promising PKCα ligand, showing a Ki value of 0.7 μM. In the present contribution our efforts are aimed at better understanding which structural modifications of the pivalate template are allowed for its affinity to the C1 domain of PKC to be preserved or increased. To this aim, thirteen novel analogues of 1 were designed and their interaction with the target was evaluated in silico. Designed compounds were then prepared and fully characterized as well as their affinity for the α and δ isoforms of PKC evaluated. Additionally, in order to investigate the role of chirality in the ligand-target interaction, the pure enantiomers of the most interesting PKC ligands were prepared and their affinity for PKC isoforms was determined. Results from our study revealed that: i) the presence of the ester function seems to be essential for the ligand-target interaction; ii) only a few structural modifications at the ester group are allowed for the C1 domain affinity to be preserved; and iii) the [3H]PDBu replacement experiments showed that the C1 domain of PKC does not exhibit enantiopreference for the pure stereoisomers of tested compounds. Altogether our observations provide further insights into the ligand-target interactions of the PKC C1 domain and represent a step-forward in future development of more specific and effective PKC ligands. This journal is
- Rossi, Daniela,Talman, Virpi,Genn?s, Gustav Boije Af,Marra, Annamaria,Picconi, Pietro,Nasti, Rita,Serra, Massimo,Ann, Jihyae,Amadio, Marialaura,Pascale, Alessia,Tuominen, Raimo K.,Yli-Kauhaluoma, Jari,Lee, Jeewoo,Collina, Simona
-
supporting information
p. 547 - 554
(2015/04/27)
-
- THIOARYL DERIVATIVES AS GPR120 AGONISTS
-
The present invention relates to thioaryl derivatives of Formula 1 as defined in the specification, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The thioaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in macrophages, pancreas cells, etc. due to anti-inflammatory action, and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, inflammation, obesity, non-alcoholic fatty liver, steatohepatitis or osteoporosis.
- -
-
Paragraph 464-466
(2014/05/24)
-
- PHENYL DERIVATIVE
-
The compound represented by the formula (I-1): wherein all the symbols have the same meanings as described in the specification, has two cyclic groups, particularly phenoxy groups at specific substitution positions and thus has high human S1P2 antagonistic activity. The compound may therefore be used as a therapeutic agent for S1P2-mediated diseases such as diseases resulting from vascular constriction, fibrosis and respiratory diseases.
- -
-
Paragraph 0120
(2014/08/19)
-
- PROCESS FOR THE PREPARATION OF O-DESMETHYL VENLAFAXINE AND INTERMEDIATE FOR USE THEREIN
-
The present invention relates to a compound of formula (A), wherein R is alkyl. Compound A may be used as an intermediate in the preparation of O-desmethyl venlafaxine or a salt thereof, and the present invention provides such a preparation, as well as a process for preparing the compound of formula (A).
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Page/Page column 14
(2011/02/24)
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- Quaternary chiral center via diastereoselective enolate amination enables the synthesis of an anti-inflammatory agent
-
The D-leucine amino acid residue necessary for the synthesis of BMS-561392,1, was employed as a chiral directing group for a diastereoselective enolate animation to establish the quaternary chiral center. Enhanced diastereomeric ratios were observed while conducting the enolate amination with 1-chloro-1-nitrosocyclo- pentane 6 in the presence of LiCl. Analogies are drawn between known tertiary amide amino alcohol chiral auxiliaries which have been used to effect diastereoselective enolate alkylations and aminations. Once the stereochemical features of 1 were established, an efficient reaction sequence was devised to complete its synthesis. During the course of this research, accelerated reaction calorimetry (ARC) data substantiated that the aminating agent 1-chloro-1- nitrosocyclopentane 6 was not safe to use as a neat compound. Consequently, a preparation and use of 6 as a stock solution in methyl tert-butyl ether (MTBE) was developed that rendered it safe for use.
- Magnus, Nicholas A.,Campagna, Silvio,Confalone, Pat N.,Savage, Scott,Meloni, David J.,Waltermire, Robert E.,Wethman, Robert G.,Yates, Mathew
-
experimental part
p. 159 - 167
(2010/04/29)
-
- Alternative total synthesis of (-)-galanthamine hydrobromide
-
An alternative total synthesis of (-)-galanthamine (1) hydrobromide, employing ecofriendly amidation, oxidative coupling, and classical resolution strategies is accomplished. Copyright Taylor & Francis Group, LLC.
- Reddy, Jambula Mukunda,Kumar, Kotagiri Vijay,Raju, Veeramalla,Bhaskar, Bolguddu Vijay,Himabindu, Vurumidi,Bhattacharya, Apurba,Sundaram, Venkatram,Banerjee, Rahul,Reddy, Ghanta Mahesh,Bandichhor, Rakeshwar
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p. 2138 - 2149
(2008/09/21)
-
- DEUTERATED AMINOGLYCIDYL COMPOUNDS
-
Provided herein are substituted aminoglycidyl compounds of Formula (1), processes of preparation, and pharmaceutical compositions thereof and methods of their use for treating, preventing, or ameliorating one or more symptoms of a social anxiety disorder, an anxiety disorder, hyperthyroidism, tremor, glaucoma, hypertension, coronary artery bypass graft, chronic stable angina, atrial arrhythmia, migraine, bleeding esophageal varices, hypertrophic subaortic stenosis, heart failure, post-myocardial infarction, decreased left ventricular function after recent myocardial infarction, and/or any disorder ameliorated by beta adrenergic receptor modulators.
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Page/Page column 76-77
(2008/06/13)
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- A-[(E)-2-(5,6,7,8-TETRAHYDRO-5,5,8,8-TETRAMETHYL-2-NAPTHALENYL)-1-PROPENYL]BENZOIC ACID ANALOGS AND METHOD OF MANUFACTURE AND AND USE THEREOF
-
Analogs of 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl)-1 - propenyl]benzoic acid and methods of manufacture and use thereof, such as for use in cancer prevention and treatment.
- -
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Page/Page column 13
(2008/06/13)
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- Synthesis of pulvinic acid and norbadione A analogues by Suzuki-Miyaura cross-coupling of benzylated intermediates
-
Pulvinic acid and norbadione A analogues can be prepared by Suzuki-Miyaura cross-coupling of functionalized aryl-boronic esters with appropriate vinyl inflates, in which the hydroxy functions are protected either with methyl or benzyl groups, the latter being cleaved in a more reliable fashion at the end of the synthetic sequence. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Murr, Marine Desage-El,Nowaczyk, Stephanie,Le Gall, Thierry,Mioskowski, Charles
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p. 1489 - 1498
(2007/10/03)
-
- Preparation of (-)-galantamine hydrobromide
-
A process for preparing (?)-galantamine hydrobromide.
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-
Page/Page column 3
(2008/06/13)
-
- Identification of a potent botulinum neurotoxin A protease inhibitor using in situ lead identification chemistry
-
Botulinum neurotoxins (BoNTs), etiological agents of the deadly food poisoning disease botulism, are the most toxic proteins currently known. By using in situ lead identification chemistry, we have uncovered the first class of inhibitors that displays nanomolar potency. From a 15 μM lead compound, structure-activity relationship studies were performed granting the most potent BoNT/A inhibitor reported to date that displays an inhibition constant of 300 nM.
- Boldt, Grant E.,Kennedy, Jack P.,Janda, Kim D.
-
p. 1729 - 1732
(2007/10/03)
-
- 2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands
-
A series of 2-benzyl and 2-phenyl-3-hydroxypropyl pivalates designed to incorporate the principal pharmacophores of phorbol esters have been synthesized and tested as PKC-α ligands. Among the analogues, 13c exhibited the most potent binding affinity with a Ki = 0.7 μM. The synthesized analogues were subjected to molecular modeling analysis based on two alternative models of the phorbol pharmacophore and a docking study of 13c was carried out.
- Lee, Jeewoo,Lee, Ju-Hyun,Kim, Su Yeon,Perry, Nicholas A.,Lewin, Nancy E.,Ayres, Jolene A.,Blumberg, Peter M.
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p. 2022 - 2031
(2007/10/03)
-
- VITRONECTIN RECEPTOR ANTAGONISTS
-
Compounds of formula (I) are disclosed which are vitronectin receptor antagonists and are useful in the treatment of osteoporosis wherein R is Het- or Ar; R is formula (a) or formula (b); or a pharmaceutically acceptable salt thereof.
- -
-
-
- Aminoalcohol derivatives
-
The present invention relates to a compound formula [I]: wherein R1 is hydrogen or halogen, R2 is hydrogen or an amino protective group, R3 is hydrogen or lower alkyl, X is bond, —CH2— or —O—, and Y is ?in which R4 is lower alkoxycarbonyl, ?in which R5 is carboxy(lower)alkyl, etc., ?in which R6 is hydroxy, etc., and so on, or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.
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-
Page/Page column 19
(2010/02/07)
-
- AMINOALCOHOL DERIVATIVES AND THEIR USE AS BETA-3 ADRENERGIC RECEPTOR AGONISTS
-
The present invention relates to a compound formula [I] or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.
- -
-
Page/Page column 57
(2010/02/07)
-
- 1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
-
The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
- -
-
-
- 4-[(8-Ethynyl, 8-vinyl or 8-ethynyl-methyl)-6-chromanoyl]-benzoic and 2-[4-[(8-ethynyl, 8-vinyl or 8-ethynyl-methyl)-6-chromanoyl]-phenyl]-acetic acid, their esters and salts having cytochrome P450RAI inhibitory activity
-
Compounds of Formula 1 1 wherein the variables are defined in the specification have cytochrome P450RAI-1 and P450RAI-2 inhibitory activity, and are suitable for treatment of mammals with conditions which are treatable with retinoids, or which are controlled by or responsive to the organism''s native retinoic acid. Formulations containing the compounds of the invention can also be co-administered with retinoids and/or Vitamin A to enhance or prolong the effects of medications containing retinoids, Vitamin A, or of the organism''s native retinoic acid.[From equivalent US6740676] Compounds of Formula 1: STR1wherein the variables are defined in the specification have cytochrome P450RAI-1 and P450RAI-2 inhibitory activity, and are suitable for treatment of mammals with conditions which are treatable with retinoids, or which are controlled by or responsive to the organism''s native retinoic acid. Formulations containing the compounds of the invention can also be co-administered with retinoids and/or Vitamin A to enhance or prolong the effects of medications containing retinoids, Vitamin A, or of the organism''s native retinoic acid.
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-
Page/Page column 10; 16
(2008/06/13)
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- PYRAZOLO` 1,5A! PYRIMIDINE COMPOUNDS AS ANTIVIRAL AGENTS
-
The invention relates to the inhibition of hepatitis C virus (HCV) replication. In particular, embodiments of the invention provide compounds and methods for inhibiting HCV RNA-dependent RNA polymerase enzymatic activity. The invention also provides compositions and methods for the prophylaxis and treatment of HCV infection.
- -
-
-
- Differential inhibition of polymerase and strand-transfer activities of HIV-1 reverse transcriptase
-
A new class of inhibitors of HIV-1 reverse transcriptase obtained by the systematic structural simplification of epicatechin and epigallocatechin gallates are also shown here to inhibit DNA-strand-transfer, a process critical to the completion of the HIV-1-RT reproduction and to recombination-associated mutation of the virus. Up to 80-fold selectivity for DNA-strand-transfer inhibition over polymerase inhibition was observed for a defined subset of these agents. Such specific DNA-strand-transfer inhibitors may have important therapeutic potential.
- Tillekeratne,Sherette, Angela,Fulmer, Jennifer A,Hupe, Lynn,Hupe, Donald,Gabbara, Sam,Peliska, James A,Hudson, Richard A
-
p. 525 - 528
(2007/10/03)
-
- Non-peptidyl inhibitors of VLA-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases
-
There is disclosed a genus of non-peptidyl compounds, wherein said compounds are VLA-4 inhibitors useful in treating inflammatory, autoimmune, and respiratory diseases, and wherein said compounds comprise a compound of Formula (1.0.0): and pharmaceutically acceptable salts and other prodrug derivatives thereof, wherein: A is (C1-C6) alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl optionally substituted with 0 to 3 R9; or is a member selected from the group consisting of the following radicals: A1-NHC(═O)NH-A2-, A1-NHC(═O)O-A2-, A1-OC(═O)NH-A2-, A1-NHSO2NH-A2-, A1-NHC(═O)-A2-, A1-C(═O)NH-A2-, A1-NHSO2-A2-, A1-SO2NH-A2-, A1-(CH2)r-A2-, where A1 and A2 are each independently selected from the group consisting of hydrogen, aryl, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, cycloalkyl, heteroaryl, and heterocyclyl substituted with 0 to 3 R9; B is a member independently selected from the group consisting of the following: E is a single bond; —O—; —NR10—; —CH═CH—; —CC—; —S(═)q; —CR11R12NR10—; or —CR11R12; X is —O—; —C(═O)—; —S(═O)q—; or —NR10—; X1, X2 and X3 are each independently selected from the group consisting of CH, CR9 or N; Y is a single bond; —C(═O)—; —C(═S)—; or —S(═O)2—; R7 is (C1-C6) alkyl; (CH2)kOR5; (CH2)kNR6C(═O)R5; (CH2)kNR6C(═O)OR5; (CH2)kNR6SO2R5; (CH2)kNR6R5; F; CF3; OCF3; aryl, substituted with 0 to 3 R9; heterocyclyl, substituted with 0 to 3 R9; heteroaryl, substituted with 0 to 3 R9; cycloalkyl, substituted with 0 to 3 R9; or R7 may be taken together with R8 to form a cycloalkyl or heterocyclyl ring; or R7 may be taken together with R11 to form a cycloalkyl or heterocyclyl ring; and R8 is hydrogen; F; (C1-C6) alkyl or (C1-C6) alkoxy.
- -
-
-
- Para-aryl or heterocyclic substituted phenyl glucokinase activators
-
Para-aryl or heteroaryl substituted phenyl amides which are active as glucokinase activators to increase insulin secretion which makes them useful for treating type II diabetes.
- -
-
-
- Head-to-Tail Connected Double Calix[4]arenes
-
New macrotricyclic compounds consisting of two calix[4]arene substructures connected by aliphatic chains of various length (three to five carbon atoms) between two opposite p-positions and two distal phenolic oxygens have been synthesized. Starting with p-tert-butyl-calix[4]arene, two O-protected phenolic units are attached via ether links in 1,3-position by reaction with the corresponding tosylates. After deprotection, the new calix[4]arene is formed by fragment condensation with 2,6-tobromomethylated 4-alkylphenols. The structure of one example (8c) has been confirmed by single crystal X-ray analysis. Both calixarene parts assume the cone conformation, a molecule of acetonitrile being included in both cavities.
- Wasikiewicz,Rokicki,Kielkiewicz,Paulus,Boehmer
-
p. 863 - 879
(2007/10/03)
-
- A concise synthetic entry to substituted 2-Aminothieno[2,3- d]pyrimidines via a Gewald precursor
-
A concise synthesis of substituted 2-aminothieno[2,3-d]pyrimidines is described based on pyrimidine annulation of tetrasubstituted thiophene precursors assembled by a Gewald thiophene ring synthesis.
- Zhang, Minsheng,Harper, Richard W.
-
p. 1629 - 1634
(2007/10/03)
-
- The Effect of Carbonyl Containing Terminal Chains on Mesomorphic Properties in 4,4'-Disubstituted Phenylbenzoates and Phenylthiobenzoates. 5. Phenylbenzoates Containing a (CH2)nO2CR' Group (n = 1,2) on the Phenolic End
-
A few homologs of the esters 2 (R' = C8H17, n= 1 or 2) and 4 (R' = C7H15) were synthesized and their mesomorphic properties determined using hot-stage polarizing microscopy.No mesophases were observed for series 2 (n = 1) or 4.This was also true for the previously reported series 1 (n = 1) and 3.Transitions temperatures for series 2 with n = 2 were lower than when n = 1 but higher than for the reverse ester series I with n = 2.In both series 1 and 2 with n = 2, only short range monotropic phases were observed.Like its parent sereis 2 (n = 0), the n = 2 esters showed various combination of nematic and smectic A, B and C, whereas the reverse esters 1 (n = 2) have only nematic and smectic A phases.The phenols required for synthesizing the esters 2 (n = 2) and 4 were prepared from the analogous protected phenolic alcohols.No suitable protecting group which could be selectively removed from the phenol could be found for synthesizing the precursor alcohol for series 2 when n = 1.Instead these esters were prepared by esterification of the appropriately 4-substituted benzoic acid with 4-hydroxybenzaldehyde, reduction to the alcohol and esterification.NMR spectra were used to confirm the structures of all intermediates and esters. Keywords: liquid crystals, phenylbenzoates, 4-substituted phenols, NMR
- Neubert, M. E.,Citano, C. M.,Ezenyilimba, M. C.,Jirousek, M. R.,Sabol-Keast, S.,Sharma, R. B.
-
p. 103 - 116
(2007/10/02)
-
- α-substituted 4-(quinolin-2-yl-methoxy)phenylacetic acids and esters and lipoxygenase inhibition therewith
-
As lipoxygenase inhibitors, the novel α-substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid and esters thereof of the formula STR1 in which R1 - stands for hydrogen, alkyl, arylalkyl, aryl or - for a group of the formula where R3 - stands for hydrogen, alkyl, arylalkyl or aryl and R2 - stands for hydrogen, alkyl, alkenyl or alkinyl, and salts thereof.
- -
-
-
- Antihypertensive dihydropyridine derivatives
-
Compound of formula 1 are calcium entry antagonists useful for treating hypertension, congestive heart failure, angina, and vasospastic disorders: STR1 wherein n is an integer from 1 to 4; R1 and R2 are lower alkyl; R3 is lower alkyl or alkoxyalkyl; A is alkylene of two to eight carbon atoms; X1 and X2 are each independently --NO2, --CF3, CH3 O--, --CN, --H, lower alkyl or halo; Y is --O--, --S--, --S(O)--, or --S(O)2 --; and R is H, lower alkyl, cycloalkyl, alkoxyalkyl, cycloalkyloxy-alkyl, alkoxycycloalkyl, acyl, or saturated or unsaturated 5- or 6-membered heterocyclyl optionally substituted with lower alkyl or alkoxy, wherein the heteroatom is one oxygen atom.
- -
-
-
- Antihypertensive dihydropyridine compositions, optical isomers and intermediates
-
Compositions containing dihydropyridine derivatives which are useful for treating congestive heart failure, hypertension, or angina have the formula: STR1 or a pharmaceutically acceptable acid addition salt thereof, wherein n is an integer from 0 to 8; Y is --O--, --NH--, --NR2 --, --S--, --S(O)--, --S(O)2 --, or a bond; R1 and R2 are each independently A1, A2, A3 or A4 where A1 is --(CH2)m (CHOH)p CH2 OH; A2 is --(CH2)q CH(3-r) [(CH2)s OH]r ; A3 is --(CH2)q CH(3-r) [(CH2)p COOR3 ]r ; and A4 is --(CH2)m COOR3 ; where m is an integer from 1 to 8; p is an integer from 0 to 4; q is an integer from 0 to 8; r is 2 or 3; s is an integer from 1 to 4; and R3 is H or alkyl of 1 to 18 carbon atoms; R4 is --NO2, --CF3, or halo; and R5 is lower alkyl or --CH2 CH2 OCH3. Also disclosed are optical isomers of the above compounds, as well as intermediates in the preparation of these final products.
- -
-
-
- In Vivo Characterization of Hydroxamic Acid Inhibitors of 5-Lipoxygenase
-
The hydroxamic acid functionality can be incorporated into simple molecules to produce potent inhibitors of 5-lipoxygenase.The ability of many of these hydroxamates to inhibit leukotriene synthesis in vivo has been measured directly with a rat peritoneal anaphylaxis model.Despite their potent enzyme inhibitory activity in vitro, many orally dosed hydroxamic acids only weakly inhibited leukotriene synthesis in vivo.This discrepancy is attributable at least in part to the rapid metabolism of hydroxamates to the corresponding carboxylic acids, which are inactive against the enzyme.A study of the structural features that affect this metabolism revealed that 2-arylpropionohydroxamic acids are relatively resistant to metabolic hydrolysis.Several members of this class of hydroxamates are described that are orally active inhibitors of leukotriene synthesis.
- Summers, James B.,Gunn, Bruce P.,Mazdiyasni, Hormoz,Goetze, Andrew M.,Young, Patrick R.,et al.
-
p. 2121 - 2126
(2007/10/02)
-
- Dioxolanones as Synthetic Intermediates. Part 2. Synthesis of Tetronic Acids and Pulvinones
-
The utility of 1,3-dioxolan-4-ones as intermediates in the synthesis of tetronic acids is examined.The reaction of dioxolanone (1) with lithium enolates of 2-substituted methyl or t-butyl acetates at -78 deg C in tetrahydrofuran afforded a general synthesis of 2-substituted tetronic acids (3) - (8).Treatment of (1) with the anions of 2-substituted acetonitriles led to formation of the corresponding 3-substituted-2-aminofuran-4(5H)-ones (13) and (14).A route to unsymmetrically substituted pulvinones by reaction of 5-arylidene-2,2-pentamethylene-1,3-dioxolan-4-ones with appropriately substituted phenylacetic ester anions has been devised.Thus, the preparation of the naturally occurring pigment 3',4',4-trihydroxypulvinone (18) was achieved via intermediate in which the phenolic groups were protected as benzyl ethers.The dioxolanone (26) has been used in the preparation of 2-acyl-4-benzylidenetetronic acids.
- Ramage, Robert,Griffiths, Gareth J.,Shutt, Fiona E.,Sweeney, John N. A.
-
p. 1539 - 1545
(2007/10/02)
-
- Synthesis of Racemic Tenellin
-
Total synthesis of racemic tenellin, a yellow pigment of the insect pathogenic fungus Beauveria, has been accomplished.Preparation of 1,4-dihydroxy-5-(p-hydroxyphenyl)-2(1H)-pyridinone is achieved in excellent overall yield by utilizing an intramolecular C-acylation of an imidazolide precursor.A facile conjugate reduction of the vinylogous amide 6 is illustrated with sodium cyanoborohydride.
- Williams, David R.,Sit, Sing-Yuen
-
p. 2846 - 2851
(2007/10/02)
-