- Preparation method and intermediate of benzoxazine dione compound C
-
The invention discloses a preparation method of a benzoxazine dione compound C and an intermediate of the benzoxazine dione compound C. The method I comprises the following steps: (1) reacting a compound SM01 with N,N'-disuccinimido carbonate to obtain an
- -
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Paragraph 0022; 0051; 0053; 0054; 0056-0059
(2021/06/06)
-
- Target protein degradation inducing compound, preparation method thereof and pharmaceutical composition for preventing or treating targeted protein related diseases containing the same as an active ingredient
-
The present invention relates to a degraducer for inducing the decomposition of target protein, a producing method thereof, and a pharmaceutical composition for preventing or treating target protein-related diseases by containing the degraducer as an active ingredient. A novel compound represented by chemical formula 1, ULB-L-PTM, by the present invention, as a degraducer compound inducing the decomposition of target protein using cereblon E3 ubiquitin ligase, is able to significantly achieve a target protein degradation-inducing activity with an excellent binding activity of a cereblon E3 ubiquitin ligase binder thereby, being able to achieve an excellent protein degradation activity by targeting protein or polypeptide related to various diseases. The bromodomain-containing pharmaceutical composition for preventing or treating protein-related diseases or conditions contains the novel compound represented by chemical formula 1 as an active ingredient and has a useful effect of providing a health functional food composition for prevention or improvement.(AA) Example 22 (nM, 24h)COPYRIGHT KIPO 2020
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Paragraph 0569; 0571-0573
(2020/05/01)
-
- NOVEL PIPERIDINE-2,6-DIONE DERIVATIVE AND USE THEREOF
-
The present disclosure relates to a novel piperidine-2,6-dione derivative and a use thereof and, more specifically, to a piperidine-2,6-dione derivative compound having a structure of a thalidomide analog. A compound of chemical formula 1 according to the present disclosure specifically binds with CRBN protein, and is involved in functions thereof. Therefore, the compound of the present disclosure can be favorably used in the prevention or treatment of leprosy, chronic graft versus host disease, an inflammatory disease, or cancer, which are caused by actions of CRBN protein.
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Paragraph 0125; 0126-0128
(2020/03/09)
-
- New spiro pyrrole[2, 1-b]quinazolone derivative, preparation method and application thereof
-
The invention relates to a new spiro pyrrole[2, 1-b]quinazolone derivative, a preparation method and application thereof. The new spiro pyrrole[2, 1-b]quinazolone derivative is synthesized by using asimple method. The yield is high, the production cost is
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-
Paragraph 0049-0051
(2020/11/09)
-
- Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita
-
A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0 mg L?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0 mg L?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.
- Chen, Xiulei,Zhou, Zhen,Li, Zhong,Xu, Xiaoyong
-
p. 194 - 200
(2019/09/13)
-
- Synthesis and nematicidal evaluation of 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker against Meloidogyne incognita
-
To explore new skeleton with nematicidal activity, a series of novel 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker were synthesized and varied fragments were also introduced to increase structure diversity of the new skeleton. Their inhibitory activities in vivo were evaluated against Meloidogyne incognita. The newly prepared compounds A6, A8, A21, A28 and A38 exhibited more than 50% inhibition at the concentration of 20 mg/L. Especially compound A6 displayed 71.4% inhibition against Meloidogyne incognita at the concentration of 20 mg/L. The nematicidal activities varied significantly depending on the types and positions of the substituents, which provided guidance for further structure modification.
- Chen, Xiulei,Jia, Haowu,Li, Zhong,Xu, Xiaoyong
-
supporting information
p. 1207 - 1213
(2019/03/29)
-
- Target Elucidation by Cocrystal Structures of NADH-Ubiquinone Oxidoreductase of Plasmodium falciparum (PfNDH2) with Small Molecule To Eliminate Drug-Resistant Malaria
-
Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states. The PfNDH2 inhibitor exhibits excellent potency against both drug-resistant strains in vitro and parasite-infected mice in vivo via a potential allosteric mechanism. Furthermore, it was found that the inhibitor can be used in combination with dihydroartemisinin (DHA) synergistically. These findings not only are important for malarial PfNDH2 protein-based drug development but could also have broad implications for other NDH2-containing pathogenic microorganisms such as Mycobacterium tuberculosis.
- Yang, Yiqing,Yu, You,Li, Xiaolu,Li, Jing,Wu, Yue,Yu, Jie,Ge, Jingpeng,Huang, Zhenghui,Jiang, Lubin,Rao, Yu,Yang, Maojun
-
supporting information
p. 1994 - 2005
(2017/03/17)
-
- Substituted aminopyrimidine compounds and their method and use thereof
-
The invention relates to a new aminopyrimidine compound and an application thereof as a drug for treating disorder or diseases related to PI3-kinase abnormity in a free form or a pharmaceutically acceptable salt and preparation form. The invention also relates to a pharmaceutical composition which contains the new aminopyrimidine compound and an application of the pharmaceutical composition in treating mammal disorder or diseases and especially treating human disorder or diseases related to the PI3-kinase abnormity, such as treatment of immunity and inflammatory diseases of PI3-kinase regulation which plays a leading role in a leucocyte function and treatment of proliferative diseases which are related to PI3-kinase activity and include but not limited to leukaemia and solid tumor.
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-
Paragraph 1445; 1446; 1447; 1448
(2017/12/28)
-
- Design, Synthesis, and Potency of Pyruvate Dehydrogenase Complex E1 Inhibitors against Cyanobacteria
-
Safe and effective algaecides are needed to control agriculturally and environmentally significant algal species. Four series (6, 10, 17, and 21) of 29 novel 4-aminopyrimidine derivatives were rationally designed and synthesized. A part of 10, 17, and 21 displayed potent inhibition of Escherichia coli pyruvate dehydrogenase complex E1 (E. coli PDHc-E1) (IC50 = 2.12-18.06 μM) and good inhibition of Synechocystis sp. PCC 6803 (EC50 = 0.7-7.1 μM) and Microcystis sp. FACH 905 (EC50 = 3.7-7.6 μM). The algaecidal activity of these compounds positively correlated with their inhibition of E. coli PDHc-E1. In particular, 21l and 10b exhibited potent algaecidal activity against PCC 6803 (EC50 = 0.7 and 0.8 μM, respectively), values that were 2-fold increased compared to that of copper sulfate (EC50 = 1.8 μM), and showed the best inhibition of cyanobacterium PDHc-E1 (IC50 = 5.10 and 6.06 μM, respectively). 17h and 21e, the best inhibitors of E. coli PDHc-E1, were studied by molecular docking, site-directed mutagenesis, and enzymatic assays. These results revealed that the improved inhibition of novel inhibitors compared with that of the lead compound I was due to the formation of a new hydrogen bond with Leu264 at the active site of E. coli PDHc-E1. The results proved the great potential to obtain effective algaecides via the rational design of PDHc-E1 inhibitors. [Figure Presented]
- Zhou, Yuan,Feng, Jiangtao,He, Hongwu,Hou, Leifeng,Jiang, Wen,Xie, Dan,Feng, Lingling,Cai, Meng,Peng, Hao
-
p. 6491 - 6502
(2017/12/26)
-
- An Efficient Method for the Synthesis of Laquinimod
-
Laquinimod, 5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N- phenyl-3-quinoline carboxamide, is an oral drug in clinical trials for the treatment of multiple sclerosis. An efficient synthetic method for laquinimod from 2-amino-6-chlorobenzoic acid via four steps was established. The overall yield of laquinimod is up to 82% as compared with 70% reported in literature. It has also been demonstrated that green reagent dimethyl carbonate is not suitable for the N-methylation of 5-chloroisatoic anhydride owing to the ring-cleavage reaction induced by the generated methanol. The ring-cleavage by-products were isolated and characterized by 1H-NMR and 13C-NMR. In addition, in the study of laquinimod derivatives, we found that 5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide (laquinimod) was obtained in much higher yield than 7-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide under the same reaction conditions, and it is possibly attributed to a neighboring group effect.
- Huang, Yanyan,Feng, Ying,Gao, Wensheng,Zhang, Chao,Chen, Ligong
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p. 437 - 440
(2016/04/19)
-
- Quinazoline dione derivatives and preparation method and application thereof
-
The invention provides novel quinazoline dione derivatives and a preparation method and application thereof. The compounds include compounds with the structure shown in the general formula V in the description and pharmaceutically acceptable salts or hydrates thereof. The compounds are active ligands of novel cannabinoid II receptors (CB2) and can be used for preparing medicine for treating, preventing and relieving CB2 receptor-mediated diseases, wherein the medicine is an agonist or partial agonist or inverse agonist or antagonist of CB2 receptors.
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-
Paragraph 0193; 0194; 0195
(2017/07/19)
-
- 1,4-benzodiazepine-2,5-diones and related compounds with therapeutic properties
-
The present invention provides novel chemical compounds characterized as Rho kinase (ROCK) inhibitors, methods for their discovery, and their therapeutic, research, and diagnostic use. In particular, the present invention provides 1,4-benzodiazepine-2,5-d
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Page/Page column 55
(2015/09/28)
-
- Structure-activity relationship and properties optimization of a series of Quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway
-
Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chemical properties of hit compound 1, our medicinal chemistry effort allowed the discovery and characterization of lead compound 33 (SEN461), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors.
- Nencini, Arianna,Pratelli, Carmela,Quinn, Joanna M.,Salerno, Massimiliano,Tunici, Patrizia,De Robertis, Alessandra,Valensin, Silvia,Mennillo, Federica,Rossi, Marco,Bakker, Annette,Benicchi, Tiziana,Cappelli, Federico,Turlizzi, Elisa,Nibbio, Martina,Caradonna, Nicola P.,Zanelli, Ugo,Andreini, Matteo,Magnani, Matteo,Varrone, Maurizio
-
supporting information
p. 526 - 545
(2015/04/14)
-
- HETEROCYCLIC COMPOUNDS AND USES THEREOF
-
Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase a
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-
Paragraph 00453
(2015/05/06)
-
- PYRIMIDINE OR PYRIDINE DERIVATIVES USEFUL AS PI3K INHIBITORS
-
Compounds (I) and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein.
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-
Paragraph 00602
(2015/11/23)
-
- Synthesis, biological evaluation and SAR of 3-benzoates of ingenol for treatment of actinic keratosis and non-melanoma skin cancer
-
Ingenol 3-benzoates were investigated with respect to chemical stability, pro-inflammatory effects, cell death induction and PKCδ activation. A correlation between structure, chemical stability and biological activity was found and compared to ingenol mebutate (ingenol 3-angelate) used for field treatment of actinic keratosis. We also provided further support for involvement of PKCδ for induction of oxidative burst and cytokine release. Molecular modeling and dynamics calculations corroborated the essential interactions between key compounds and C1 domain of PKCδ.
- Grue-Sorensen, Gunnar,Liang, Xifu,Mansson, Kristoffer,Vedso, Per,Dahl Sorensen, Morten,Soor, Anke,Stahlhut, Martin,Bertelsen, Malene,Engell, Karen Margrethe,Hoegberg, Thomas
-
-
- TREATMENT OF DISEASES BY EPIGENETIC REGULATION
-
The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of diseases or disorders that are susceptible to administration of a BET inhibitor.
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-
Paragraph 0488; 0489
(2013/11/05)
-
- COMPOSITIONS AND METHODS OF TREATING A DISEASE WITH (S)-4 AMINO-6-((1-(5-CHLORO-4-OXO-3-PHENYL-3,4-DIHYDROQUINAZOLIN-2-YL)ETHYL)AMINO)PYRIMIDINE-5-CARBONITRILE
-
Provided are methods that relate to a novel therapeutic strategy for the treatment of asthma. In particular, the method comprises administration of Compound A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising such compound admixed with at least one pharmaceutically acceptable excipient.
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-
Paragraph 0107
(2013/08/15)
-
- COMPOSITIONS AND METHODS OF TREATING A PROLIFERATIVE DISEASE WITH A QUINAZOLINONE DERIVATIVE
-
Provided are methods that relate to a novel therapeutic strategy for the treatment of cancers. In particular, the method comprises administration of Compound A, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising such compound admixed with at least one pharmaceutically acceptable excipient.
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-
Paragraph 0131
(2013/06/26)
-
- A phosgene and peroxide-free one-pot tandem synthesis of isatoic anhydrides involving anthranilic acid, boc anhydride and 2-chloro-N-methyl pyridinium iodide
-
A phosgene and peroxide-free approach for the synthesis of isatoic anhydrides has been described. The synthesis involves the carbamate formation with boc anhydride followed by in situ cyclization to afford the isatoic anhydride. The importance of this synthetic strategy is in the ease of operation, scalability and preparation from readily available raw materials.
- Verma, Chhaya,Sharma, Somesh,Pathak, Arunendra
-
p. 6897 - 6899
(2019/04/10)
-
- MACROCYCLIC KINASE INHIBITORS
-
Compounds of Formula (I): wherein variables are defined herein, and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancers for which FAK inhibition is beneficial.
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Page/Page column 80
(2012/06/16)
-
- Synthesis, biological assessment and molecular modeling of new dihydroquinoline-3-carboxamides and dihydroquinoline-3-carbohydrazide derivatives as cholinesterase inhibitors, and Ca channel antagonists
-
The synthesis, biological evaluation, and molecular modeling of new 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides(4), 4-hydroxy-2-oxo-1,2- dihydroquinoline-3-carbohydrazide (6), and some hexahydropyrimido[5,4-c] quinoline-2,5-diones (9) produced earlier by our laboratory, as AChE/BuChE inhibitors, is described. From these analyses compound 4c resulted equipotent regarding the inhibition of cholinesterases'; inhibitors 6k, 9a, 9b were selective for AChE, whereas product 4d proved selective for BuChE. Docking analysis has been carry out in order to identify the binding mode in the active site, and to explain the observed selectivities. Only compound 9a has been shown to decrease K+-induced calcium signals in bovine chromaffin cells.
- Tomassoli, Isabelle,Ismaili, Lhassane,Pudlo, Marc,De Los Ríos, Cristóbal,Soriano, Elena,Colmena, Inés,Gandía, Luis,Rivas, Luis,Samadi, Abdelouahid,Marco-Contelles, José,Refouvelet, Bernard
-
experimental part
p. 1 - 10
(2011/02/27)
-
- NOVEL ANTI-INFLAMMATORY AGENTS
-
Disclosed are methods of regulating interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1) and methods of treating and/or preventing cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s) by administering a naturally occurring or synthetic quinazolone derivative. The invention provides novel synthetic quinazolone compounds, as well as pharmaceutical compositions comprising those compounds.
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Page/Page column 100-101
(2010/11/05)
-
- Development of a practical and reliable synthesis of laquinimod
-
Laquinimod(5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl- 3-quinoline carboxamide) is a drug candidate for treatment of Multiple Sclerosis. A short and industrially feasible process for the preparation of laquinimod starting from 2-amino-6-chlorobenzoic acid, in essentially four steps, is discussed. The key step is a novel reaction in which a methyl ester is converted to an amide in very high yield and with excellent purity. The present article elucidates the scale-up process along with safety aspects and the impurity profiles of the intermediates and product. Initial laboratory conditions are described as well as the changes made on transfer to pilot-plant scale.
- Wennerberg, Johan,Bjoerk, Anders,Fristedt, Tomas,Granquis, Bo,Jansson, Karl,Thuvesson, Ingela
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p. 674 - 680
(2012/12/29)
-
- QUINOLONE BASED COMPOUNDS EXHIBITING PROLYL HYDROXYLASE INHIBITORY ACTIVITY, AND COMPOSITIONS, AND USES THEREOF
-
This invention relates to new quinolone based compounds that exhibit prolyl hydroxylase inhibitory activity. This invention also relates to methods of increasing HIF levels or activity in a subject or treating a condition associated with HIF levels or activity in a subject by administering to the subject at least one quinolone based compound. This invention further involves assays for the detection of a hydroxyproline residue in a HIF molecule.
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Page/Page column 8
(2011/07/06)
-
- Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids
-
A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while -OCH3, CH3, and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn2+ but did not result in enhancement in potency. Introduction of a tertiary amino moiety at the ortho-position of the sulfonyl phenyl ring gave reduced protein binding and improved cellular activity, but led to lower oral bioavailability.
- Wang, Gary T.,Mantei, Robert A.,Kawai, Megumi,Tedrow, Jason S.,Barnes, David M.,Wang, Jieyi,Zhang, Qian,Lou, Pingping,Garcia, Lora A.,Bouska, Jennifer,Yates, Melinda,Park, Chang,Judge, Russell A.,Lesniewski, Richard,Sheppard, George S.,Bell, Randy L.
-
p. 2817 - 2822
(2008/02/03)
-
- 3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase
-
Recently, we disclosed a new class of HCV polymerase inhibitors discovered through high-throughput screening (HTS) of the GlaxoSmithKline proprietary compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4- benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV polymerase enzymatic activity and inhibits the ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This report will focus on the structure-activity relationships (SAR) of substituents on the quinolinone ring, culminating in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4- benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency in biochemical and cellular assays possessing attractive molecular properties for advancement as a clinical candidate. The potential for development and safety assessment profile of compound 130 will also be discussed.
- Tedesco, Rosanna,Shaw, Antony N.,Bambal, Ramesh,Chai, Deping,Concha, Nestor O.,Darcy, Michael G.,Dhanak, Dashyant,Fitch, Duke M.,Gates, Adam,Gerhardt, Warren G.,Halegoua, Dina L.,Han, Chao,Hofmann, Glenn A.,Johnston, Victor K.,Kaura, Arun C.,Liu, Nannan,Keenan, Richard M.,Lin-Goerke, Juili,Sarisky, Robert T.,Wiggall, Kenneth J.,Zimmerman, Michael N.,Duffy, Kevin J.
-
p. 971 - 983
(2007/10/03)
-
- PIPERIDINE DERIVATIVES HAVING CCR3 ANTAGONISM
-
The invention provides low molecular compounds having activity which inhibits binding of CCR3 ligands to CCR3 on target cells, i.e. CCR3 antagonists. The invention also provides compounds represented by formula (I) below, pharmaceutically acceptable acid adducts thereof, or pharmaceutically acceptable C1-C6 alkyl adducts thereof, as well as pharmaceutical compositions comprising them as effective ingredients, which are useful for treatment or prevention of diseases associated with CCR3, such as asthma and allergic rhinitis.
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-
- Anti-infective agents
-
Compounds having the formula are hepatitis C(HCV) polymerase inhibitors. Also disclosed are a composition and method for inhibiting hepatitis C(HCV) polymerase, processes for making the compounds, and synthetic intermediates employed in the processes.
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-
-
- Anti-infective agents
-
Compounds having the formula are hepatitis C (HCV) polymerase inhibitors. Also disclosed are a composition and method for inhibiting hepatitis C (HCV) polymerase, processes for making the compounds, and synthetic intermediates employed in the processes.
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-
-
- Anti-infective agents
-
The present invention provides an HCV polymerase inhibiting compound having the formula (I) and a composition comprising a therapeutically effective amount of said compound. The present invention also provides a method for inhibiting hepatitis C virus (HC
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Page/Page column 98
(2010/02/08)
-
- Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders: Structure-Activity Relationship
-
Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure-activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II).
- J?nsson, Stig,Andersson, Gunnar,Fex, Tomas,Fristedt, Tomas,Hedlund, Gunnar,Jansson, Karl,Abramo, Lisbeth,Fritzson, Ingela,Pekarski, Olga,Runstr?m, Anna,Sandin, Helena,Thuvesson, Ingela,Bj?rk, Anders
-
p. 2075 - 2088
(2007/10/03)
-
- PROCESS FOR THE MANUFACTURE OF QUINOLINE DERIVATIVES
-
A process for the preparation of the compounds of general formula (I); by reacting a quinoline-3-carboxylic acid ester derivative of formula A with an aniline derivative of formula B in a solvent selected from straight- or branch-chaineded alkanes and cycloalkanes or mixtures thereof with a boiling point between 80 and 200 C.
- -
-
-
- QUINOLINE DERIVATIVES
-
The invention is related to compounds of general formula (I), wherein R is methyl, ethyl, n-propyl, iso-propyl, n-butyl or allyl; R' is methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, or OCHxFy, wherein x = O - 2, y = 1 - 3 with the proviso that x + y = 3; R'' is hydrogen, fluoro or chloro; with the proviso that R'' is fluoro or chloro only when R' is fluoro; R4 is hydrogen or pharmaceutically acceptable inorganic or organic cations; R5 is ethyl, n-propyl, iso-propyl, methoxy, ethoxy, chloro, bromo, trifluoromethyl, OCHxFy, or OCH2CHxFy wherein x = 0 - 2, y = 1 - 3 with the proviso that x + y = 3; R6 is hydrogen; or R5, and R6 taken together are methylenedioxy; and any tautomer thereof. The invention also relates to pharmaceutical compositions containing a compound of general formula (I) together with a pharmaceutically acceptable carrier. Included are also processes for the preparation of the compounds of formula (I), as well as methods for the treatment of mammals suffering from diseases resulting from autoimmunity and pathological inflammation by administering of a compound having formula (I) to said mammal.
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-
Page/Page column 6
(2008/06/13)
-
- Pyridazinedione compounds useful in treating neurological disorders
-
The present invention relates to pyridazino[4,5-b]quinolines, and pharmaceutically useful salts thereof, which are excitatory amino acid antagonists and which are useful when such antagonism is desired such as in the treatment of neurological disorders. The invention further provides pharmaceutical compositions containing pyridazino[4,5-b]quinolines as active ingredient, and methods for the treatment of neurological disorders.
- -
-
-
- Tricyclic heterocyclic compounds as psychopharmaceuticals
-
New heterocyclic compounds having the general formula STR1 wherein STR2 CO2 R' or CONR'R", wherein R' and R" independently are C1-6 -alkyl, C3-7 -cycloalkyl or C1-6 -alkoxymethyl; --A-- is --C(=O)--NR'"--, --NR'"--C(=O)--, or STR3 wherein R'" is C1-6 -alkyl; X is C or N; and R4 is hydrogen, halogen, CN, C1-6 -alkyl, C1-6 -alkynyl, trimethylsilyl-C1-6 -alkynyl, aryloxy which may be substituted with halogen, aralkoxy, C3-7 -cycloalkoxy which may be substituted with one or more C1-6 -alkyl groups, or NR""R'"", wherein R"" and R'"" independently are C1-6 -alkoxy or together with the nitrogen atom form a 3-7 membered heterocyclic ring. The compounds are useful in psychopharmaceutical preparations as anticonvulsants, anxiolytics, hypnotics, and nootropics.
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