- INHIBITORS TO TARGET HIV-1 NEF-CD80/CD86 INTERACTIONS FOR THERAPEUTIC INTERVENTION
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The compounds of Formula I, II, and III along with their stereoisomers, pharmaceutically acceptable salts, polymorphs, solvates and hydrates thereof are described in the present disclosure. The said compounds restore immune activation in case of infections or a disease associated with an HIV infection in a subject in need thereof.
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- Synthesis, evaluation and in silico molecular modeling of pyrroyl-1,3,4-thiadiazole inhibitors of InhA
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Enoyl acyl carrier protein reductase (ENR) is an essential type II fatty acid synthase (FAS-II) pathway enzyme that is an attractive target for designing novel antitubercular agents. Herein, we report sixty-eight novel pyrrolyl substituted aryloxy-1,3,4-thiadiazoles synthesized by three-step optimization processes. Three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for pyrrolyl substituted aryloxy-1,3,4-thiadiazole series of InhA inhibitors using the comparative molecular field analysis (CoMFA). Docking analysis of the crystal structure of ENR performed by using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of pyrrolyl substituted aryloxy 1,3,4-thiadiazole into hydrophobic pocket of InhA enzyme. Based on docking and database alignment rules, two computational models were established to compare their statistical results. The analysis of 3D contour plots allowed us to investigate the effect of different substituent groups at different positions of the common scaffold. In vitro testing of ligands using biological assays substantiated the efficacy of ligands that were screened through in silico methods.
- Joshi, Shrinivas D.,More, Uttam A.,Koli, Deepshikha,Kulkarni, Manoj S.,Nadagouda, Mallikarjuna N.,Aminabhavi, Tejraj M.
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p. 151 - 167
(2015/03/30)
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- Copper(ii)-catalyzed C-O coupling of aryl bromides with aliphatic diols: Synthesis of ethers, phenols, and benzo-fused cyclic ethers
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A highly efficient copper-catalyzed C-O cross-coupling reaction between aryl bromides and aliphatic diols has been developed employing a cheaper, more efficient, and easily removable copper(ii) catalyst. A broad range of aryl bromides were coupled with aliphatic diols of different lengths using 5 mol% CuCl2 and 3 equivalents of K2CO3 in the absence of any other ligands or solvents to afford the corresponding hydroxyalkyl aryl ethers in good to excellent yields. In this newly developed protocol, aliphatic diols have multilateral functions as coupling reactants, ligands, and solvents. The resulting hydroxyalkyl aryl ethers were further readily converted into the corresponding phenols, presenting a valuable alternative way to phenols from aryl bromides. Furthermore, it was demonstrated that they are useful intermediates for more advanced molecules such as benzofurans and benzo-fused cyclic ethers. This journal is
- Liu, Yajun,Park, Se Kyung,Xiao, Yan,Chae, Junghyun
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supporting information
p. 4747 - 4753
(2014/06/24)
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- PRODRUGS OF PEPTIDE EPOXY KETONE PROTEASE INHIBITORS
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This disclosure features compounds that are useful as pro-drugs of epoxy ketone protease inhibitors.
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- Copper(II)-catalyzed hydroxylation of aryl halides using glycolic acid as a ligand
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Copper(II)-catalyzed hydroxylation of aryl halides has been developed to afford functionalized phenols. The protocol utilizes the reagent combination of Cu(OH)2, glycolic acid, and NaOH in aqueous DMSO, all of which are cheap, readily available, and easily removable after the reaction. A broad range of aryl iodides and activated aryl bromides were transformed into the corresponding phenols in excellent yields. Moreover, it has been shown that C-O(alkyl)-coupled product, instead of phenol, can be predominantly formed under similar reaction conditions.
- Xiao, Yan,Xu, Yongnan,Cheon, Hwan-Sung,Chae, Junghyun
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p. 5804 - 5809
(2013/07/25)
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- Synthesis and insect antifeedant activity of aurones against spodoptera litura larvae
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A series of aurones were prepared from various phenols via phenoxy acetic acids and coumaranones and evaluated for insect antifeedant activity against the common cutworm (Spodoptera litura). The naturally occurring aurone was most active at an ED50 of 0.12 μmol/cm2. The synthetic precursor, coumaranones, showed that the introduction of methoxyl and methyl groups to the benzene ring increased insect antifeedant activity. Similarly, the tested aurones showed that the introduction of methoxyl group to the A and/or B rings increased the insect antifeedant activity, but 4,5,6- and 3 ,4 ,5 -trisubstituted compounds did not show this activity in this test. The hydroxylation of aurones in the B ring should be disadvantageous for insect antifeedant activity against S. litura. Although the melting points did not correlate well with the insect antifeedant activity, compounds that were nearly inactive had high melting points. A significant correlation was noted between biological activity (pED50) and a hydrogen-bonding parameter calculated from the Rf value obtained from SiOH thin-layer chromatography and a lipophilicity parameter (log k) calculated from the retention time in ODS high-performance liquid chromatography. The respective correlation coefficients (r) were -0.83 and -0.70. The introduction of alkoxy and alkyl groups along with adequate hydrogen bonding seems to contribute to the antifeedant activity of the compounds tested.
- Morimoto, Masanori,Fukumoto, Hiromi,Nozoe, Toki,Hagiwara, Ai,Komai, Koichiro
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experimental part
p. 700 - 705
(2009/10/01)
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- Process for preparing isomerically pure prodrugs of proton pump inhibitors
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Synthetic methods for preparing isomerically pure N-arylsulfonyl derivatives of proton pump inhibitors which include a substituted benzimidazole nucleus are shown by the synthetic schemes and experimental description.
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Page/Page column 32
(2010/02/10)
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- PRODRUGS OF PROTON PUMP INHIBITORS
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Prodrugs of proton pump inhibitors of Formulas 1 through 4, (I-IV), where the symbols are as defined in the specification, and the R group includes at least one acidic group or its pharmaceutically acceptable salt, have improved aqueous solubility and bioavailability.
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- Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists
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Since its discovery in 1988 by Yanagisawa et al., endothelin (ET), a potent vasoconstrictor, has been widely implicated in the pathophysiology of cardiovascular, cerebrovascular, and renal diseases. Many research groups have embarked on the discovery and development of ET receptor antagonists for the treatment of such diseases. While several compounds, e.g., ambrisentan 2, are in late clinical trials for various indications, one compound (bosentan, Tracleer) is being marketed to treat pulmonary arterial hypertension. Inspired by the structure of ambrisentan 2, we designed a novel class of ET receptor antagonists based on a 1,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-one scaffold. Here, we report on the preparation as well as the in vitro and in vivo structure-activity relationships of these derivatives. Potent dual ET A/ETB receptor antagonists with affinities in the low nanomolar range have been identified. In addition, several compounds efficiently reduced arterial blood pressure after oral administration to Dahl salt sensitive rats. In this animal model, the efficacy of the benzo[e] [1,4]diazepin-2-one derivative rac-39au was superior to that of racemic ambrisentan, rac-2.
- Bolli, Martin H.,Marfurt, Judith,Grisostomi, Corinna,Boss, Christoph,Binkert, Christoph,Hess, Patrick,Treiber, Alexander,Thorin, Eric,Morrison, Keith,Buchmann, Stephan,Bur, Daniel,Ramuz, Henri,Clozel, Martine,Fischli, Walter,Weller, Thomas
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p. 2776 - 2795
(2007/10/03)
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- Method for treating glaucoma IIB
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Provided is a method of decreasing intraocular pressure or improving ocular accommodation in an animal, including a human, comprising administering an intraocular pressure decreasing amount or ocular accommodation improving amount of a compound of the formula I or IA, wherein J is oxygen, sulfur, or N—Rd.
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- Synthesis and structure-activity relationships of a novel series of HIV-1 protease inhibitors encompassing ABT-378 (Lopinavir)
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The HIV protease inhibitor ABT-378 (Lopinavir) has a 2,6-dimethylphenoxyacetyl group in the P-2′ position. Analogues in which this group is replaced with various substituted phenyl or heteroaryl groups were synthesized and the structure-activity relationships explored.
- Sham, Hing L.,Betebenner, David A.,Chen, Xiaoqi,Saldivar, Ayda,Vasavanonda, Sudthida,Kempf, Dale J.,Plattner, Jacob J.,Norbeck, Daniel W.
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p. 1185 - 1187
(2007/10/03)
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- Heteroaromatic diphosphines as chiral ligands
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Chiral diphosphines constituted by an aromatic pentatomic biheterocyclic system, suitable to act as chiral ligands, complexes between said diphosophines and transition metals, and their utilization as chiral catalysts in sterocontrolled reactions, such as diastereo- and enantioselective reduction reactions. Process for the preparation of said chiral diphosophines and process for the preparation of said complexes and for their utilization as chiral catalysts in sterocontrolled reactions.
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- Environmentally desirable synthesis without use of organic solvent. Synthesis of aryloxyacetic acids
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A process using only water as solvent is described for the synthesis of aryloxyacetic acids under microwave irradiation.
- Villemin, Didier,Hammadi, Mohamed
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p. 4337 - 4341
(2007/10/03)
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- Design, Synthesis, and Testing of Potential Antisickling Agents. 4. Structure-Activity Relationships of Benzyloxy and Phenoxy Acids
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In this paper we further establish the activity of two classes of small molecules, benzyloxy and phenoxy acids, as potent inhibitors of hemoglobin S (HbS) gelation.Structural modifications with a large number of each class confirm our earlier work that the highest activity is observed with compounds that contain dihalogenated aromatic rings with attached polar side chains.We have also found a halogenated aromatic malonic acid derivative to be quite active.Compounds reported in this paper are compared with other antigelling agents studied in our laboratory.Comments are made concerning the antigelling activity and binding sites of four derivatives and their effect on the allosteric mechanism of hemoglobin (Hb) function.
- Abraham, D. J.,Kennedy, P. E.,Mehanna, A. S.,Patwa, D. C.,Williams, F. L.
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p. 967 - 978
(2007/10/02)
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