- Contrast agent iopromide intermediate as well as preparation method and application thereof
-
The invention discloses a contrast agent iopromide intermediate as well as a preparation method and application thereof, and belongs to the technical field of organic chemistry. The iopromide intermediate is N-(2, 3-dihydroxy-propyl)-5-nitroisophthalic acid methyl ester. According to the preparation method, the iopromide intermediate is synthesized through two steps, the product obtained in the reaction in the step (1) can directly participate in the reaction in the step (2) without a complex purification process, the product obtained in the step (2) does not need a time-consuming, labor-consuming and money-consuming purification method such as column chromatography and does not need a recrystallization method which can cause a great loss of the product, the high-purity iopromide intermediate can be obtained only through simple extraction, the purity is larger than 99.5%, and the yield can reach 70-80%. Therefore, when the intermediate is used for preparing iopromide, the price of iopromide can be greatly reduced.
- -
-
Paragraph 0031; 0037; 0041
(2021/05/29)
-
- Preparation method and application of iopromide intermediate (by machine translation)
-
The invention relates to a preparation method of an iopromide intermediate and an application thereof in preparation of iopromide. The method comprises the following steps: compound VI compound is subjected to reduction reaction under the action of Raney nickel/hydrazine hydrate to obtain the compound V compound. The reaction is carried out under normal pressure, the operation is simple and safe, the generated intermediate impurities are less, and the reaction is more suitable for industrial production. The method is used for preparing iopromide, can avoid the generation of a diacylated by-product, can effectively reduce the generation of by-products in the preparation process, can be easily separated and purified, and can obtain high-purity iopromide with high yield. (by machine translation)
- -
-
Paragraph 0059-0061
(2020/07/24)
-
- Preparation methods of iopromide and intermediate of iopromide
-
The application of the invention relates to preparation methods of iopromide and an intermediate of the iopromide. The method specifically comprises the following steps: conducting a reduction reaction, an iodination reaction and an acylation reaction on a compound shown in the formula VI to prepare a compound shown in the formula III, and further preparing to obtain the iopromide. The method notonly avoids the generation of double acylation byproducts, but also effectively reduces the generation of byproducts in the preparation process, the intermediate is easy to separate and purify, and ahigh-purity product is obtained at a relatively high yield.
- -
-
Paragraph 0058-0060
(2018/03/24)
-
- BIS AROMATIC COMPOUNDS FOR USE AS LCT4 SYNTHASE INHIBITORS
-
There is provided compounds of formula I, wherein Y, ring A, Da, Db, D2, D3, L1, Y1, L2, Y2, L3 and Y3 have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of leukotriene C4 synthase is desired and/or required, and particularly in the treatment of a respiratory disorder and/or inflammation.
- -
-
Page/Page column 67
(2010/10/03)
-
- Discovery of a synthetic dual inhibitor of HIV and HCV infection based on a tetrabutoxy-calix[4]arene scaffold
-
A potential anti-HIV and HCV drug candidate is highly desirable as coinfection has become a worldwide public health challenge. A potent compound based on a tetrabutoxy-calix[4]arene scaffold that possesses dual inhibition for both HIV and HCV is described. Structural activity relationship studies demonstrate the effects of lower-rim alkylation in maintaining cone conformation and upper-rim interacting head groups on the calix[4]arene play key roles for its potent dual antiviral activities.
- Tsou, Lun K.,Dutschman, Ginger E.,Gullen, Elizabeth A.,Telpoukhovskaia, Maria,Cheng, Yung-Chi,Hamilton, Andrew D.
-
scheme or table
p. 2137 - 2139
(2010/06/22)
-
- BENZOXAZOLES USEFUL IN THE TREATMENT OF INFLAMMATION
-
There is provided the use of a compound of formula (I): wherein Y, W1 to W4, Z1 to Z4 and R have meanings given in the description, and pharmaceutically-acceptable salts thereof, for the manufacture of a medicament for the treatment of a disease in which inhibition of the activity of a member of the MAPEG family is desired and/or required, and particularly in the treatment of inflammation.
- -
-
Page/Page column 56; 62
(2008/12/06)
-
- MACROCYCLIC COMPOUNDS USEFUL AS BACE INHIBITORS
-
The invention relates to novel macrocyclic compounds of the Formula (I) in which all of the variables are as defined in the specification, in free base form or in acid addition salt form, to their preparation, to their use as medicaments and to medicaments comprising them.
- -
-
Page/Page column 31-32
(2008/06/13)
-
- From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part I: The discovery of CCR3 antagonist development candidate BMS-639623 with picomolar inhibition potency against eosinophil chemotaxis
-
Conformational analysis of trans-1,2-disubstituted cyclohexane CCR3 antagonist 2 revealed that the cyclohexane linker could be replaced by an acyclic syn-α-methyl-β-hydroxypropyl linker. Synthesis and biological evaluation of mono- and disubstituted propyl linkers support this conformational correlation. It was also found that the α-methyl group to the urea lowered protein binding and that the β-hydroxyl group lowered affinity for CYP2D6. Ab initio calculations show that the α-methyl group governs the spatial orientation of three key functionalities within the molecule. α-Methyl-β-hydroxypropyl urea 31 with a chemotaxis IC50 = 38 pM for eosinophils was chosen to enter clinical development for the treatment of asthma.
- Santella III, Joseph B.,Gardner, Daniel S.,Yao, Wenqing,Shi, Chongsheng,Reddy, Prabhakar,Tebben, Andrew J.,DeLucca, George V.,Wacker, Dean A.,Watson, Paul S.,Welch, Patricia K.,Wadman, Eric A.,Davies, Paul,Solomon, Kimberly A.,Graden, Dani M.,Yeleswaram, Swamy,Mandlekar, Sandhya,Kariv, Ilona,Decicco, Carl P.,Ko, Soo S.,Carter, Percy H.,Duncia, John V.
-
p. 576 - 585
(2008/09/19)
-
- New anti-viral drugs for the treatment of the common cold
-
Human Rhinovirus (HRV) is the most important aetiologic agent of common cold in adults and children. HRV is a single-stranded, positive sense RNA virus and, despite the high level of conservation among different serotypes, sequence alignment of viral protease 3C with mammalian protease reveals no homology. Thus, protease 3C is an optimal target for the development of anti-HRV agents. In the present work we investigated the design, the synthesis and the development of new potential reversible inhibitors against HRV protease 3C. Docking studies on the crystallized structure of HRV2 protease 3C led us to the design and the synthesis of a series of 3,5 disubstituted benzamides able to act as analogues of the substrate. We also developed 1,3,5 trisubstituted benzamides where aromatic substitutions on the aryl ring led us to investigate the importance of π-π interaction on the stabilization of protease 3C-inhibitor complex. All structures were tested for enzymatic inhibition on HRV14 protease 3C. Results highlighted the inhibitory activity of compounds 13, 14, and 20 (91%, 81%, and 85% at 10 μM, respectively), with the latter exhibiting an ID50 (dose that inhibits 50% of the viral cytopathic effect) on HRV-14 = 25 μg/ml.
- Maugeri, Caterina,Alisi, Maria A.,Apicella, Claudia,Cellai, Luciano,Dragone, Patrizia,Fioravanzo, Elena,Florio, Saverio,Furlotti, Guido,Mangano, Giorgina,Ombrato, Rosella,Luisi, Renzo,Pompei, Raffaello,Rincicotti, Vito,Russo, Vincenzo,Vitiello, Marco,Cazzolla, Nicola
-
p. 3091 - 3107
(2008/09/20)
-
- Macrocyclic Compounds Useful as Bace Inhibitors
-
The invention relates to novel macrocyclic compounds of the formula (I), in which all of the variables are as defined in the specification, the number of ring atoms included in the macrocyclic ring being 14, 15, 16 or 17, in free base form or in acid addition salt form, to their preparation, to their use as medicaments and to medicaments comprising them.
- -
-
Page/Page column 30
(2008/12/05)
-
- Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2
-
Analogues of the hexapeptide angiotensin IV (Ang IV, Val1-Tyr2-Ile3-His4-Pro5-Phe6) encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2 and a phenylacetic or benzoic acid moiety replacing His4-Pro5-Phe6 have been synthesized and evaluated in biological assays. The analogues inhibited the proteolytic activity of cystinyl aminopeptidase (CAP), frequently referred to as the insulin-regulated aminopeptidase (IRAP), and were found less efficient as inhibitors of aminopeptidase N (AP-N). The best Ang IV mimetics in the series were approximately 20 times less potent than Ang IV as IRAP inhibitors. Furthermore, it was found that the ligands at best exhibited a 140 times lower binding affinity to the membrane-bound IRAP/AT4 receptor than Ang IV. Although the best compounds still exert lower activities than Ang IV, it is notable that these compounds comprise only two amino acid residues and are considerably less peptidic in character than the majority of the Ang IV analogues previously reported as IRAP inhibitors in the literature.
- Andersson, Hanna,Demaegdt, Heidi,Vauquelin, Georges,Lindeberg, Gunnar,Karlen, Anders,Hallberg, Mathias
-
p. 6924 - 6935
(2008/12/22)
-
- Benzoylurea derivatives as a novel class of antimitotic agents: Synthesis, anticancer activity, and structure-activity relationships
-
Forty-six new compounds were synthesized on the basis of our knowledge of the 3-haloacylamino benzoylurea (HBU) series. Structure-activity relationship (SAR) analysis indicates that (i) the configuration of the chiral center in 1 (JIMB01) is not indispensable for the activity, (ii) the phenyl ring is essential, and (iii) a substitution at the 6-position of the phenyl ring with a halogen enhances the activity. Among the analogues, 11e and 14b bearing 6-fluoro substitution showed potent activities against nine human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), PC-3 (prostate cancer), DND-1A(melanoma), LOVO (colon cancer), and MIA Paca (pancreatic cancer) with IC50 values between 0.01 and 0.30 μM. 14b inhibited human hepatocarcinoma by 86% in volume in nude mice. The mechanism of 14b is to inhibit microtubule assembly, followed by the M-phase arrest, bcl-2 inactivation, and then apoptosis. We consider 14b promising for further anticancer investigation.
- Song, Dan-Qing,Wang, Yan,Wu, Lian-Zong,Yang, Peng,Wang, Yue-Ming,Gao, Li-Mei,Li, Yan,Qu, Jing-Rong,Wang, Yong-Hong,Li, Ying-Hong,Du, Na-Na,Han, Yan-Xing,Zhang, Zhi-Ping,Jiang, Jian-Dong
-
experimental part
p. 3094 - 3103
(2009/04/06)
-
- THERAPEUTIC COMPOUNDS
-
This invention relates to a novel class of substituted amino-ethoxy benzene derivatives of formula (I) which are inhibitors of serine proteases and to their use in treating aberrant serine protease activity in a mammal, contraception, anti-coagulant methods and methods for treating aberrant cell proliferation, tumours, cancer, angiogenesis, angiogenesis-based retinopathies, autoimmummune disease, inflammation, skin disease, arthritis, rheutmatoid arthritis, asthma, osteoarthritis and multiple sclerosis. (I), Wherein Rm, Rn, Rp, Rq, V, W, X, Y and R8 are as defined in the claims.
- -
-
Page/Page column 71
(2010/11/27)
-
- Nitrogen-containing heterocycle derivatives, pharmaceutical compositions, and methods of use thereof as antiviral agents
-
The present application provides nitrogen-containing heterocycle derivatives that are antiviral compounds that may be useful in the treatment of a viral infection. Compounds of Formula (I) and pharmaceutical compositions comprising a compound of Formula (I) may be administered to a subject for antiviral therapy or prophylaxis.
- -
-
Page/Page column 34
(2010/11/28)
-
- N-PHENYL BENZAMIDE DERIVATIVES AS SIRTUIN MODULATORS
-
Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treatin and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
- -
-
Page/Page column 138; 139; 144
(2008/06/13)
-
- Structure-activity studies on a library of potent calix[4]arene-based PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation
-
Platelet-derived growth factor (PDGF) and its receptor PDGFR are required for tumor growth and angiogenesis, so disruption of the PDGF-PDGFR interaction should lead to starvation of tumors and reduction of tumor growth. Potent PDGF antagonists have been discovered through the synthesis of a series of calix[4]arene-based compounds that are designed to bind to the three-loop region of PDGF. The effect of lower-rim alkylation, linker and number of interacting head groups on the calix[4]arene scaffold on PDGF affinity and cellular activity has been investigated. The Royal Society of Chemistry 2006.
- Zhou, Huchen,Wang, De-An,Baldini, Laura,Ennis, Eileen,Jain, Rishi,Carie, Adam,Sebti, Said M.,Hamilton, Andrew D.
-
p. 2376 - 2386
(2008/09/19)
-
- PHENYL-SULFAMATES AS AROMATASE INHIBITORS
-
There is provided a compound of Formula (I) wherein X, Y and Z are each independently of each other an optional linker group; R, is a ring system; R2 is selected from hydrocarbyl groups, oxyhydrocarbyl groups, cyano (CN), nitro (-NO2) and halogens; R3 and R4 are independently selected from H and hydrocarbyl, ring A and B are independently optionally further substituted.
- -
-
Page/Page column 69
(2008/06/13)
-
- Angiotensin II pseudopeptides containing 1,3,5-trisubstituted benzene scaffolds with high AT2 receptor affinity
-
Two 1,3,5-trisubstituted aromatic scaffolds intended to serve as γ-turn mimetics have been synthesized and incorporated in five pseudopeptide analogues of angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe), replacing Val-Tyr-Ile, Val-Tyr, or Tyr-Ile. All the tested compounds exhibited nanomolar affinity for the AT2 receptor with the best compound (3) having a Ki of 1.85 nM. Four pseudopeptides were AT2 selective, while one (5) also exhibited good affinity for the AT1 receptor (Ki = 30.3 nM). This pseudopeptide exerted full agonistic activity in an AT2 receptor induced neurite outgrowth assay but displayed no agonistic effect in an AT1 receptor functional assay. Molecular modeling, using the program DISCOtech, showed that the high-affinity ligands could interact similarly with the AT2 receptor as other ligands with high affinity for this receptor. A tentative agonist model is proposed for AT2 receptor activation by angiotensin II analogues. We conclude that the 1,3,5-trisubstituted benzene rings can be conveniently prepared and are suitable as γ-turn mimics.
- Georgsson, Jennie,Sk?ld, Christian,Plouffe, Bianca,Lindeberg, Gunnar,Botros, Milad,Larhed, Mats,Nyberg, Fred,Gallo-Payet, Nicole,Gogoll, Adolf,Karlén, Anders,Hallberg, Anders
-
p. 6620 - 6631
(2007/10/03)
-
- N-UREIDOALKYL-PIPERIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY.
-
The present application describes N-ureidoalkyl piperidines as modulators of chemokine receptors, or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
- -
-
-
- Refinement and evaluation of a pharmacophore model for flavone derivatives binding to the benzodiazepine site of the GABAA receptor
-
To further develop and evaluate a pharmacophore model previously proposed by Cook and co-workers (Drug Des. Discovery 1995, 12, 193-248) for ligands binding to the benzodiazepine site of the GABAA receptor, 40 new flavone derivatives have been synthesized and their affinities for the benzodiazepine site have been determined. Two new regions of steric repulsive interactions between ligand and receptor have been characterized, and the receptor region in the vicinity of 6- and 3′-substituents has been mapped out. 2′-Hydroxy substitution is shown to give a significant increase in affinity, which is interpreted in terms of a novel hydrogen bond interaction with the previously proposed hydrogen bond-accepting site A2. On the basis of the results of these studies and the refined pharmacophore model, 5′-bromo-2′-hydroxy-6-methylflavone, the highest affinity flavone derivative reported so far (Ki = 0.9 nM), was successfully designed. A comparison of the pharmacophore model with a recently proposed alternative model (Marder; et al. Bioorg. Med. Chem., 2001, 9, 323-335) has been made.
- Kahnberg, Pia,Lager, Erik,Rosenberg, Celia,Schougaard, Jette,Camet, Linda,Sterner, Olov,Nielsen, Elsebet ?stergaard,Nielsen, Mogens,Liljefors, Tommy
-
p. 4188 - 4201
(2007/10/03)
-
- Pyrimidin derivatives
-
The invention relates to new pharmaceutically active compounds which are are P2-purinoceptor 7-transmembrane (TM) G-protein coupled receptor antagonists, compositions containing them and processes for their preparation.
- -
-
-
- Utility of Complementary Molecular Reactivity and Molecular Recognition (CMR/R) Technology and Polymer-Supported Reagents in the Solution-Phase Synthesis of Heterocyclic Carboxamides
-
The use of our recently reported chemical library purification strategy in the development of a herbicidal lead, N-(3-benzoylphenyl)-3-(1,1-dimethylethyl)-1-methyl-1H-pyrazole-5-carboxamide (3), is described. The approach applying fundamental properties of complementary molecular reactivity and molecular recognition (CMR/R) as the basis for a general purification strategy was utilized. Polymeric reagents were used in the synthesis to generate reactive species involved in product formation, and complementary molecular reactivity/molecular recognition polymer 8 (CMR/R polymer 8) was used in the solution-phase syntheses of building blocks, primary libraries, and lead refinement libraries. An extension of the CMR/R methodology was applied, utilizing a sequestration enabling reagent (SER), transforming a reactant into an electrophilic species sequestrable by CMR/R polymer 8. This library purification strategy enabled rapid lead generation and lead refinement to afford herbicide 27o. The CMR/R solid-phase purification technique enabled a simple, general, and powerful protocol, eliminating the usual tedious and time-consuming methods required for solution-phase product purification. The result was the synthesis of hundreds of compounds, prepared in a relatively short time, leading to a compound with a 4-fold improvement in herbicidal activity over the initial lead.
- Parlow, John J.,Mischke, Deborah A.,Woodard, Scott S.
-
p. 5908 - 5919
(2007/10/03)
-
- Design and synthesis of benzoic acid derivatives as influenza neuraminidase inhibitors using structure-based drug design
-
A series of 94 benzoic acid derivatives was synthesized and tested for its ability to inhibit influenza neuraminidase. The enzyme-inhibitor complex structure was determined by X-ray crystallographic analysis for compounds which inhibited the enzyme. The most potent compound tested in vitro, 5 (4- (acetylamino)-3-guanidinobenzoic acid), had an IC50 = 2.5 x 10-6 M against N9 neuraminidase. Compound 5 was oriented in the active site of the neuraminidase in a manner that was not predicted from the reported active site binding of GANA (4) with neuraminidase. In a mouse model of influenza, 5 did not protect the mice from weight loss due to the influenza virus when dosed intranasally.
- Chand, Pooran,Babu, Yarlagadda S.,Bantia, Shanta,Chu, Naiming,Cole, L. Brent,Kotian, Pravin L.,Laver, W. Graeme,Montgomery, John A.,Pathak, Ved P.,Petty, Sandra L.,Shrout, David P.,Walsh, David A.,Walsh, Gerald M.
-
p. 4030 - 4052
(2007/10/03)
-
- Ureylene naphthalene sulfonic acids
-
Ureylenebis-symmetrical-phenenylbiscarbonylimino-substituted phenylenecarbonylimino-tetranaphthalenepolysulfonic acid benzoic acid salts, and nitro- and amino-substituted phenylenebiscarbonylimino-substituted benzamido-phenylenedicarbonyl-dinaphthalenepolysulfonic acid benzoic acid salts which are intermediates for the preparation of the active ureides which have complement inhibiting activity.
- -
-
-