- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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A pharmaceutical composition comprising the compound of Formula Ia, Formula Ib, Formula Ic, or Formula Id, or a pharmaceutically acceptable salt thereof, is set forth. (Formula Ia), (Formula Ib), (Formula Ic), (Formula Id)
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- TRICYCLIC PYRIDONES AND PYRIMIDONES
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A compound of Formula (I) is provided: (I) where the variables are defined herein.
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Paragraph 0500; 0534-0536
(2021/06/26)
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- INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE
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There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the disclosure.
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- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Compounds of Formula (I), including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth:
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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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p. 4208 - 4226
(2020/07/06)
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- ACLY INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of ATP citrate lyase (ACLY), compositions thereof, and methods of using the same.
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Paragraph 00738
(2020/06/01)
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- Method for preparing 7-halo-6-nitro-1,4-dihydroquinoline-4-one-3-carbonitrile
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The invention discloses a method for preparing 7-halo-6-nitro-1,4-dihydroquinoline-4-one-3-carbonitrile. The method comprises the following steps of: S1, adopting 2-amino-4-halo benzoic acid as a starting material, and performing esterification on simple fatty alcohol under the action of a catalyst so as to produce 4-halo-2-aminobenzoate; S2, performing a reaction between 4-halo-2-aminobenzoate and 3-dimethylaminoacrylonitrile under the action of an acidic catalyst so as to produce 4-halo-2-((2-cyanovinyl)amino) benzoate; S3, performing cyclization on 4-halo-2-((2-cyanovinyl)amino) benzoate under the action of strong base so as to produce 7-halo-1,4-dihydroquinoline-4-one-3-carbonitrile; and S4, performing nitrification on 7-halo-1,4-dihydroquinoline-4-one-3-carbonitrile in the presence ofa mixture of strong acid and nitric acid to obtain 7-halo-6-nitro-1,4-dihydroquinoline-4-one-3-carbonitrile. According to the method for preparing 7-halo-6-nitro-1,4-dihydroquinoline-4-one-3-carbonitrile, the process route is novel, the novel intermediates are obtained, and the total yield is more than 35%; the method has the advantages of a novel process route, mild reaction conditions and the like.
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Paragraph 0026
(2018/07/30)
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- Identification of potent and selective small molecule inhibitors of the cation channel TRPM4
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Background and Purpose: TRPM4 is a calcium-activated non-selective cation channel expressed in many tissues and implicated in several diseases, and has not yet been validated as a therapeutic target due to the lack of potent and selective inhibitors. We sought to discover a novel series of small-molecule inhibitors by combining in silico methods and cell-based screening assay, with sub-micromolar potency and improved selectivity from previously reported TRPM4 inhibitors. Experimental Approach: Here, we developed a high throughput screening compatible assay to record TRPM4-mediated Na+ influx in cells using a Na+-sensitive dye and used this assay to screen a small set of compounds selected by ligand-based virtual screening using previously known weakly active and non-selective TRPM4 inhibitors as seed molecules. Conventional electrophysiological methods were used to validate the potency and selectivity of the hit compounds in HEK293 cells overexpressing TRPM4 and in endogenously expressing prostate cancer cell line LNCaP. Chemical chaperone property of compound 5 was studied using Western blots and electrophysiology experiments. Key Results: A series of halogenated anthranilic amides were identified with TRPM4 inhibitory properties with sub-micromolar potency and adequate selectivity. We also showed for the first time that a naturally occurring variant of TRPM4, which displays loss-of-expression and function, is rescued by the most promising compound 5 identified in this study. Conclusions and Implications: The discovery of compound 5, a potent and selective inhibitor of TRPM4 with an additional chemical chaperone feature, revealed new opportunities for studying the role of TRPM4 in human diseases and developing clinical drug candidates.
- Ozhathil, Lijo Cherian,Delalande, Clémence,Bianchi, Beatrice,Nemeth, Gabor,Kappel, Sven,Thomet, Urs,Ross-Kaschitza, Daniela,Simonin, Céline,Rubin, Matthias,Gertsch, Jürg,Lochner, Martin,Peinelt, Christine,Reymond, Jean-Louis,Abriel, Hugues
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supporting information
p. 2504 - 2519
(2018/05/03)
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- Iodine(III) Reagent-Mediated Intramolecular Amination of 2-Alkenylanilines to Prepare Indoles
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A variety of 3-substituted and 2,3-disubstituted indoles were synthesized efficiently in good yields through the intramolecular amination of 2-alkenylanilines promoted by readily available iodine(III) reagents in a short reaction time. Mechanistic studies showed that the reaction pathway went through a nitrenium ion and that 3-acetoxy indoline was the key intermediate in the indole formation. The indole product was easily prepared on a gram scale and amination also proceeded smoothly using catalytic 3,5-dimethylphenyl iodine in the presence of mCPBA. Furthermore, the indolo[3,2-a]carbazole scaffold was prepared in good yield in six steps from commercial ortho-iodoaniline. (Figure presented.).
- Zhao, Chun-Yang,Li, Kun,Pang, Yu,Li, Jia-Qing,Liang, Cui,Su, Gui-Fa,Mo, Dong-Liang
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supporting information
p. 1919 - 1925
(2018/03/28)
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- A kind of novel 4,5-substituted-7-carboxylic acid methyl ester indole dione derivatives and their use in anti-tumor drug
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The invention relates to a kind of novel 4,5-substituted-7-methyl formate indoledione derivatives and an application thereof in anti-tumor drugs. The derivatives are 4-floro-5-bromo-7-methyl formate indoledione, 4-floro-5-nitro-7-methyl formate indoledione, 4-chloro-5-bromo-7-methyl formate indoledione, 4,5-dibromo-7-methyl formate indoledione and the like. In the invention, the kind of 4,5-substituted-7-methyl formate indoledione derivatives are synthesized and tested for the in-vitro tumor cell inhibition activity, and the result indicates that the kind of derivatives realize certain inhibition effects (IC5010muM) on the human leukemia cell (K562), human colon cancer cell (HT-29) and human liver cancer cell (HepG2) and have broad prospects in the development and application of anti-tumor drugs.
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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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p. 8332 - 8338
(2013/12/04)
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- Hofmann-type rearrangement of imides by in situ generation of imide-hypervalent iodines(III) from iodoarenes
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The Hofmann-type rearrangement of aromatic and aliphatic imides using a hypervalent iodine(III) reagent generated in situ from PhI, m-CPBA, and TsOH·H2O proceeded in the presence of a base in alcohol to provide anthranilic acid derivatives and amino acid derivatives in high yields, respectively. This reaction proceeds through a tandem reaction via alcoholysis followed by a Hofmann rearrangement promoted by the formation of an imide-λ3-iodane intermediate.
- Moriyama, Katsuhiko,Ishida, Kazuma,Togo, Hideo
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supporting information; experimental part
p. 946 - 949
(2012/05/05)
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- NEUROTRYPSIN INHIBITORS
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The invention relates to acylamino-phthalic acid amides and related compounds of formula (I) wherein A is -CONR3R4,-NR5COR6, -NHR7, -OR8, -mR9, -CH2NRI0R11, -(CH2)2-R12, -CH=CH-R12, -C=C-R12, optionally substituted phenyl, optionally substituted thiophenyl, or optionally substituted 1,2,3-triazol-4-yl, W is hydrogen, hydroxy or carboxymethoxy, Y is carboxy, methoxycarbonyl or 2H-tetrazol-5-yl, and the various substituents R have the meanings indicated in the description. These compounds are useful for the treatment and/or prophylaxis of skeletal muscle atrophy, schizophrenia and Alzheimer?s disease, and as cognitive enhancers.
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Page/Page column 111
(2012/05/20)
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- NOVEL ANTHRANILIC ACID DERIVATIVE OR SALT THEREOF
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The anthranilic acid derivative or the salt thereof represented by the general formula wherein R1 and R2 are hydrogen atom, or the like; R3 is a phenyl, cycloalkyl or bicyclic heterocyclic group which may be substituted, or the like; R4 is a phenyl, cycloalkyl or pyridyl group which may be substituted, or the like; X1 is an alkylene or alkenylene group which may be substituted or a bond; X2 is the general formula -X3-X4- or -X4-X3-, wherein X3 is a sulfur atom, an imino group or a bond, or the like; X4 means an alkylene or alkenylene group which may be substituted or a bond; is useful for a remedy such as rheumatoid arthritis, osteoarthritis and carcinoma, because it shows MMP-13 production inhibitory effect.
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- NOVEL ANTHRANILIC ACID DERIVATIVE OR SALT THEREOF
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An anthranilic acid derivative represented by the general formula (X) [wherein R1 represents hydrogen or a carboxy-protecting group; R2 represents optionally substituted phenyl, a heterocyclic group, etc.; R3 represents op
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- Identification and optimization of anthranilic sulfonamides as novel, selective cholecystokinin-2 receptor antagonists
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A high throughput screening approach to the identification of selective cholecystokinin-2 receptor (CCK-2R) ligands resulted in the discovery of a novel series of antagonists, represented by 1-[2-[(2,1,3-benzothiadiazol-4- ylsulfonyl)amino]-5-chlorobenzoy
- Allison, Brett D.,Phuong, Victor K.,McAtee, Laura C.,Rosen, Mark,Morton, Magda,Prendergas, Clodagh,Barrett, Terry,Lagaud, Guy,Freedman, Jamie,Li, Na,Wu, Xiaodong,Venkatesan, Hariharan,Pippel, Marna,Woods, Craig,Rizzolio, Michèle C.,Hack, Michael,Hoey, Kenway,Deng, Xiaohu,King, Christopher,Shankley, Nigel P.,Rabinowitz, Michael H.
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p. 6371 - 6390
(2008/04/18)
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- SULFONAMIDE COMPOUNDS
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Certain sulfonamide compounds are dual CCK1/CCK2 inhibitors useful in the treatment of CCK1/CCK2 mediated diseases.
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Page/Page column 29; 61
(2010/10/20)
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- NOVEL ANTHRANILIC ACID DERIVATIVE OR SALT THEREOF
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An anthranilic acid derivative represented by the general formula (X) [wherein R1 represents hydrogen or a carboxy-protecting group; R2 represents optionally substituted phenyl, a heterocyclic group, etc.; R3 represents optionally substituted phenyl, a monocyclic heterocyclic group, etc.; X1 represents carbonyl, etc.; X2 represents optionally substituted alkylene, a bond, etc.; X3 represents oxygen, a bond, etc.; and X4 represents a group represented by the general formula -X5-X6- or -X6-X5- (wherein X5 means oxygen, a bond, etc.; and X6 means optionally substituted alkylene, a bond, etc.)] or a salt of the derivative. The derivative or salt has an MMP-13 production inhibitory activity and is hence useful as a therapeutic agent for articular rheumatisum, osteoarthritis, cancer, etc.
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Page/Page column 56-57
(2008/06/13)
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- PIPERAZINYLPHENALKYL LACTAM/AMINE LIGANDS FOR THE 5HT1B RECEPTOR
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The present invention relates to novel derivatives, that are compounds of Formula (I), wherein R1, R2, R3, R14, X, Y, n and m are defined herein, their pharmaceutically acceptable salts, pharmaceutical compositions and methods using said compounds in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which selective antagonists, inverse agonists and partial agonists of serotonin 1 (5-HT1) receptors, specifically, antagonists of 5-HT1B are useful.
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Page/Page column 77
(2010/11/30)
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- AMIDE COMPOUNDS AS ION CHANNEL LIGANDS AND USES THEREOF
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Compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.
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Page/Page column 51
(2008/06/13)
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- Quinoxaline compounds
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Certain amidophenyl-sulfonylamino-quinoxaline compounds are CCK2 modulators useful in the treatment of CCK2 mediated diseases.
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Page/Page column 11
(2008/06/13)
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- COMPOUNDS AND METHODS FOR TREATING DYSLIPIDEMIA
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Compounds of formula I wherein n, m, p, q, Y, R1 R2, R3, R4, R5, and R6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating artherosclerosis and its sequelae.
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Page/Page column 51
(2008/06/13)
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- Indole derivatives
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Compounds of formula (I) or salts or solvates thereof or physiologically functional derivatives thereof are potent binders at the EP4 receptor and are of use in the treatment or prevention of conditions such as a pain, inflammatory, immunological, bone, n
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- Benzo[1,2,5]thiadiazole compounds
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Certain amidophenyl-sulfanylamino-benzo[1,2,5]thiadiazole compounds are CCK2 modulators useful in the treatment of CCK2 mediated diseases.
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- HETERO-BIARYL-PYRIDOQUINAZOLINONE DERIVATIVES AS ANTI-CANCER AGENTS
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The invention provides a compound having the formula (1), wherein (A) n = 2-4; (B) R1 and R2 are the same or different and selected from the group consisting of H, (C1-C3) alkyl, -CH2CH2OH, -CH2CH2NH2, and -CH2CH2N(CH3)2 or R1 and R2 are alkyl moieties which are taken together to form a 4- to 7-membered ring; (C) R3 is selected from the group consisting of H, -CH3, -CH2CH3, and -CH2CH2NH2; (D) Y is a heterocyclic radical having 5-14 atoms, located at the 2- or 3-position of the pyridoquinazolinone nucleus, in which 1-3 of the heterocyclic ring atoms are independently nitrogen, oxygen, or sulfur; wherein Y may be optionally mono-, di-, or tri-substituted with -OR4, -NR5R6, -CO2H, -CO2R4, or phenyl; R4 is H or (C1-C4) straight-chain alkyl; R5 and R6 are the same or different and are selected from the group consisting of H, (C1-C4) straight-chain alkyl, -CH2CH2OH, -CH2CH2NH2, and -CH2CH2N(CH3)2 or R5 and R6 are alkyl moieties which are taken together to form a 4-7 membered ring; or a pharmaceutically acceptable salt thereof which is useful as an antineoplastic agent.
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- Hetero-biaryl-pyridoquinazolinone derivatives as anti-cancer agents
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This invention provides a compound having the formula: STR1 wherein: (A) n=2-4; (B) R1 and R2 are the same or different and selected from the group consisting of H, (C1 -C3) alkyl, --CH2 CH2 OH, --CH2 CH2 NH2, and --CH2 CH2 N(CH3)2 or R1 and R2 are alkyl moieties which are taken together to form a 4- to 7- membered ring; (C) R3 is selected from the group consisting of H, --CH3, --CH2 CH3, and --CH2 CH2 NH2 ; (D) Y is a heterocyclic radical having 5-14 atoms, located at the 2- or 3- position of the pyridoquinazolinone nucleus, in which 1-3 of the heterocyclic ring atoms are independently nitrogen, oxygen, or sulfur; wherein Y may be optionally mono-, di-, or tri- substituted with --OR4, --NR5 R6, --CO2 H, --CO2 R4, or phenyl; R4 is H or (C1 -C 4) straight-chain alkyl; R5 and R6 are the same or different and are selected from the group consisting of H, (C1 -C4) straight-chain alkyl, --CH2 CH2 OH, --CH2 CH2 NH2, and --CH2 CH2 N(CH3)2 or R5 and R6 are alkyl moieties which are taken together to form a 4-7 membered ring; or a pharmaceutically acceptable salt thereof which is useful as an antineoplastic agent.
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- 4H-3,1-BENZOXAZIN-4-ONES AND RELATED COMPOUNDS AND USE AS ENZYME INHIBITORS
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Novel 2-amino-4H-3,1-benzoxazin-4-ones represented by the formula wherein R 1, R 2, R 3 and X are defined herein are useful as enzyme inhibitors in animals.
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