- Cyano ketoprofen synthesis process
-
The invention relates to a cyano ketoprofen synthesis process, which comprises the following steps: acylating chlorination, chlorination, esterification, cyaniding, distillation, methylation, hydrolysis, refining, acylation Friedel-Crafts ice precipitation distillation, and refining to finally obtain the cyano ketoprofen finished product. According to the cyano ketoprofen synthesis process, the synthesized product is low in cost, by acylating chlorination, esterification, cyaniding, methylation, Friedel-Crafts acylation and hydrolysis reaction, the product is prepared from m-toluic acid as a starting material, the process and the operation process are simplified, the safety and the reliability are provided, the wastewater and the waste gas generated during the reaction process are recycled, and the residue generated in the kettle is subjected to hazardous waste treatment, such that the environment is protected, the industrial production is promoted, the production efficiency is improved, and the purity of the synthesized finished product achieves 99% or more.
- -
-
Paragraph 0010; 0012; 0014
(2020/09/30)
-
- Radical cyanomethylation via vinyl azide cascade-fragmentation
-
Herein, a novel methodology for radical cyanomethylation is described. The process is initiated by radical addition to the vinyl azide reagent 3-azido-2-methylbut-3-en-2-ol which triggers a cascade-fragmentation mechanism driven by the loss of dinitrogen and the stabilised 2-hydroxypropyl radical, ultimately effecting cyanomethylation. Cyanomethyl groups can be efficiently introduced into a range of substrates via trapping of α-carbonyl, heterobenzylic, alkyl, sulfonyl and aryl radicals, generated from a variety of functional groups under both photoredox catalysis and non-catalytic conditions. The value of this approach is exemplified by the late-stage cyanomethylation of pharmaceuticals.
- Donald, James R.,Berrell, Sophie L.
-
p. 5832 - 5836
(2019/06/17)
-
- Preparation method of m-cyanomethyl methyl benzoate
-
The invention discloses a preparation method of m-cyanomethyl methyl benzoate. According to the method, m-bromobenzoic acid is used as a starting raw material; the m-bromine methyl methyl benzoate is prepared through esterification; m-methoxy formyl phenethyl alcohol is obtained and prepared through Grignard reaction; through oxidization, the m-methoxy formyl phenylacetic acid is prepared; through amidation and dewatering, the m-cyanomethyl methyl benzoate is finally prepared. The preparation method provided by the invention has the advantages that the design is ingenious; the route is novel; the raw materials have low price and can be easily obtained; the process is simple; the implementation is easy; the yield is high; the purity of the obtained final product is high; the quality is high; no dangerous process exists; the extremely toxic substances of cyanides and expensive cyaniding reagents used in the conventional synthesis are avoided; the requirements on the equipment are simple; the production difficulty and the production cost investment are reduced; the industrial production can be favorably realized; the economic benefits are good.
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-
-
- Palladium-Catalyzed, ortho-Selective C-H Halogenation of Benzyl Nitriles, Aryl Weinreb Amides, and Anilides
-
A palladium-catalyzed, ortho-selective C-H halogenation methodology is reported herein. The highlight of the work is the highly selective C(sp2)-H functionalization of benzyl nitriles in the presence of activated C(sp3)-H bond, which results in good yields of the halogenated products with excellent regioselectivity. Along with benzyl nitriles, aryl Weinreb amides and anilides have been evaluated for the transformation using aprotic conditions. Mechanistic studies yield interesting aspects with respect to the pathway of the reaction and the directing group abilities.
- Das, Riki,Kapur, Manmohan
-
p. 1114 - 1126
(2018/06/18)
-
- HIGHLY WATER-SOLUBLE SALTS OF A SHORT ACTING PHENYLALKYLAMINE CALCIUM CHANNEL BLOCKER AND USES THEREOF
-
The present invention includes surprisingly water-soluble salts of a phenylalkylamine compound that are potent antagonists of L-type calcium channels. Aqueous solutions including salts of the instant invention are formulated for nasal administration and provide a novel therapeutic platform for the treatment of stable angina, migraine, and cardiac arrhythmia, such as paroxysmal supraventricular tachycardia.
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Page/Page column 22
(2016/11/02)
-
- BIARYL AMIDE COMPOUNDS AS KINASE INHIBITORS
-
The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.
- -
-
Paragraph 0182
(2014/09/29)
-
- THIENO (2, 3B) PYRAZINE COMPOUNDS AS B-RAF INHIBITORS
-
The invention relates to compounds according to general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of cancer.
- -
-
Paragraph 0104
(2013/04/10)
-
- Novel symmetrical ureas as modulators of protein arginine methyl transferases
-
Methylation of histone arginine residues is an epigenetic mark related to gene expression that is implicated in a variety of biological processes and can be reversed by small-molecule modulators of protein arginine methyltransferases (PRMTs). A series of symmetrical ureas, designed as analogues of the known PRMT1 inhibitor AMI-1 have been synthesized using Pd-catalyzed Ar-N amide bond formation processes or carbonylation reactions as key steps. Their inhibitory profile has been characterized. The enzymatic assays showed a weak effect on PRMT1 and PRMT5 activity for most of the compounds. The acyclic urea that exhibited the strongest effect on the inhibition of the PRMT1 activity also showed the greatest effect on the expression of some androgen receptor target genes (TMPRSS2 and FKBP5), which may be related with its enzymatic activity. Surprisingly, AMI-1 behaved as an activator of PRMT5 activity, a result not reported so far.
- Fontán, Noelia,García-Domínguez, Patricia,álvarez, Rosana,De Lera, ángel R.
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p. 2056 - 2067
(2013/05/09)
-
- Design and synthesis of novel DFG-Out RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors. 1. Exploration of [5,6]-fused bicyclic scaffolds
-
To develop RAF/VEGFR2 inhibitors that bind to the inactive DFG-out conformation, we conducted structure-based drug design using the X-ray cocrystal structures of BRAF, starting from an imidazo[1,2-b]pyridazine derivative. We designed various [5,6]-fused bicyclic scaffolds (ring A, 1-6) possessing an anilide group that forms two hydrogen bond interactions with Cys532. Stabilizing the planarity of this anilide and the nitrogen atom on the six-membered ring of the scaffold was critical for enhancing BRAF inhibition. The selected [1,3]thiazolo[5,4-b]pyridine derivative 6d showed potent inhibitory activity in both BRAF and VEGFR2. Solid dispersion formulation of 6d (6d-SD) maximized its oral absorption in rats and showed significant suppression of ERK1/2 phosphorylation in an A375 melanoma xenograft model in rats by single administration. Tumor regression (T/C = -7.0%) in twice-daily repetitive studies at a dose of 50 mg/kg in rats confirmed that 6d is a promising RAF/VEGFR2 inhibitor showing potent anticancer activity.
- Okaniwa, Masanori,Hirose, Masaaki,Imada, Takashi,Ohashi, Tomohiro,Hayashi, Youko,Miyazaki, Tohru,Arita, Takeo,Yabuki, Masato,Kakoi, Kazuyo,Kato, Juran,Takagi, Terufumi,Kawamoto, Tomohiro,Yao, Shuhei,Sumita, Akihiko,Tsutsumi, Shunichirou,Tottori, Tsuneaki,Oki, Hideyuki,Sang, Bi-Ching,Yano, Jason,Aertgeerts, Kathleen,Yoshida, Sei,Ishikawa, Tomoyasu
-
experimental part
p. 3452 - 3478
(2012/06/17)
-
- Rhodium-catalyzed asymmetric hydrogenation of olefins with PhthalaPhos, a new class of chiral supramolecular ligands
-
A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (Phthala- Phos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97% ee), methyl (Z)-2- acetamido cinnamate (6 ligands gave >94% ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95% ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1- yl)-acetamide (96% ee in one case) and methyl (E)-2-(acetamidomethyl)-3- phenylacrylate (99% ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.
- Pignataro, Luca,Boghi, Michele,Civera, Monica,Carboni, Stefano,Piarulli, Umberto,Gennari, Cesare
-
supporting information; experimental part
p. 1383 - 1400
(2012/03/27)
-
- DISUBSTITUTED MALEIC ANHYDRIDES WITH ALTERED KINETICS OF RING CLOSURE
-
We describe anhydride compounds suitable for physiologically labile modification of amine- containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.
- -
-
Page/Page column 28-29
(2013/02/28)
-
- THIENO (2, 3B) PYRAZINE COMPOUNDS AS B - RAF INHIBITORS
-
The invention relates to compounds according to general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of cancer.
- -
-
Page/Page column 25
(2011/12/14)
-
- SEPIAPTERIN REDUCTASE INHIBITORS FOR THE TREATMENT OF PAIN
-
Disclosed herein are small molecule heterocyclic inhibitors of sepiapterin reductase (SPR), and pro-drugs and pharmaceutically acceptable salts thereof. The Also featured are pharmaceutical compositions of the compounds and uses of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, and neuropathic pain)
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-
Page/Page column 89
(2011/05/05)
-
- HETEROCYCLIC COMPOUND AND USE THEREOF
-
Disclosed is a heterocyclic compound having a strong Raf inhibitory activity. Specifically disclosed is a compound represented by the formula (I), (II) or (III) below, or a salt thereof. (In the formulae, the symbols are as defined in the description.)
- -
-
Page/Page column 65; 110; 115
(2010/06/11)
-
- Phthalaphos: Chiral supramolecular ligands for enantioselective rhodium-catalyzed hydrogenation reactions
-
Interligand hydrogen bonding of chiral monodentate phosphite ligands bearing H-bond donor and acceptor groups leads to formation of supramolecular bidentate ligands, rhodium complexes of which (see picture) afford excellent enantiomeric excesses in catalyzed hydrogenation of classical benchmark and industrially relevant substrates. cod=1,5-cyclooctadiene.
- Pignataro, Luca,Carboni, Stefano,Civera, Monica,Colombo, Raffaele,Piarulli, Umberto,Gennari, Cesare
-
supporting information; experimental part
p. 6633 - 6637
(2010/10/21)
-
- QUINAZOLINONE DERIVATIVES HAVING B-RAF INHIBITORY ACTIVITY
-
The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
- -
-
Page/Page column 11
(2009/07/17)
-
- Identification of amidoheteroaryls as potent inhibitors of mutant (V600E) B-Raf kinase with in vivo activity
-
A series of amidoheteroaryl compounds were designed and synthesized as inhibitors of B-Raf kinase. Several compounds from the series show excellent potency in biochemical, phenotypic and mode of action cellular assays. Potent examples from the series have also demonstrated good plasma exposure following an oral dose in rodents and activity against the Ras-Raf pathway in tumor bearing mice.
- Lyne, Paul D.,Aquila, Brian,Cook, Donald J.,Dakin, Les A.,Ezhuthachan, Jay,Ioannidis, Stephanos,Pontz, Timothy,Su, Mei,Ye, Qing,Zheng, Xiaolan,Block, Michael H.,Cowen, Scott,Deegan, Tracy L.,Lee, John W.,Scott, David A.,Custeau, Dominique,Drew, Lisa,Poondru, Srinivasu,Shen, Minhui,Wu, Allan
-
scheme or table
p. 1026 - 1029
(2009/08/15)
-
- ANTIVIRAL COMPOUNDS AND USE THEREOF
-
The invention relates to compounds, pharmaceutical compositions and methods useful for treating viral infection.
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-
Page/Page column 30
(2009/12/02)
-
- Versatile and fluoride-free cyanation of alkyl halides and sulfonates with trimethylsilyl cyanide
-
Cyanation of biphenyl-4-ylmethyl methanesulfonate with trimethylsilyl cyanide using fluoride-free inorganic salts, such as Cs2CO 3, K2CO3, and LiOH·H2O, as additives in MeCN quantitatively gave biphenyl-4-ylacetonitrile. This methodology was applied to various alkyl halides to give the corresponding nitrile compounds in good to excellent yields. Of note, 4-(hydroxymethyl) benzyliodide O-protected by the silyl group was converted into phenylacetonitrile derivative in 99% yield without desilylation. Georg Thieme Verlag Stuttgart.
- Yabe, Osamu,Mizufune, Hideya,Ikemoto, Tomomi
-
experimental part
p. 1291 - 1294
(2009/10/23)
-
- FUSED HETEROCYCLIC DERIVATIVE AND USE THEREOF
-
The present invention provides a fused heterocyclic derivative having a potent kinase inhibitory activity and use thereof. A compound represented by the formula (I): wherein each symbol is as defined in the specification, except a particular compound, or a salt thereof, and a pharmaceutical agent containing the compound or a prodrug thereof, which is a kinase (VEGFR, VEGFR2, PDGFR, Raf) inhibitor, an angiogenesis inhibitor, an agent for the prophylaxis or treatment of cancer, a cancer growth inhibitor or a cancer metastasis suppressor.
- -
-
-
- ANTIVIRAL COMPOUNDS AND USE THEREOF
-
The invention relates to compounds, pharmaceutical compositions and methods useful for treating viral infection.
- -
-
Page/Page column 46-47
(2008/12/08)
-
- SHORT ACTING PHENYLALKYLAMINE CALCIUM CHANNEL BLOCKERS AND USES THEREOF
-
The present invention relates to the use of a pharmaceutically effective amount of an short-acting calcium channel blocking compound to treat ischemic heart conditions, cardiac arrhythmias, hypertensive crisis in an emergency room setting, hypertension before, during, or after surgery, no- reflow phenomenon following reperfusion, and diseases associated with decreased skeletal muscle blood flow. The invention also relates to pharmaceutical compositions formulated for use in such methods and to kits for such methods.
- -
-
Page/Page column 59
(2009/01/23)
-
- CHEMICAL COMPOUNDS
-
The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof of the formula which possess CSF 1R kinase inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
- -
-
Page/Page column 50-51
(2008/06/13)
-
- CHEMICAL COMPOUNDS
-
The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
- -
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Page/Page column 47
(2008/06/13)
-
- SUBSTITUTED QUINAZOLINES WITH ANTI-CANCER ACTIVITY
-
The invention relates to chemical compounds of the formula (I): or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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-
Page/Page column 26-27
(2008/06/13)
-
- NOVEL DIAZASPIROALKANES AND THEIR USE FOR TREATMENT OF CCR8 MEDIATED DISEASES
-
The invention provides compounds of general formula (I) wherein A, B, p, w, x, y, and z are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
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Page/Page column 83
(2008/06/13)
-
- PYRIDINE CARBOXAMIDE DERIVATIVES FOR USE AS ANTICANCER AGENTS
-
The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof of the formula (I): (A chemical formula should be inserted here - please see paper copy enclosed herewith) (I) which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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-
Page/Page column 126
(2008/06/13)
-
- CHEMICAL COMPOUNDS
-
The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof, of the formula (I): which possess B-Raf inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.
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Page/Page column 34
(2008/06/13)
-
- QUINAZOLINONE DERIVATIVES AND THEIR USE AS B-RAF INHIBITORS
-
The invention relates to chemical compounds of the formula (I): or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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Page/Page column 63-64
(2008/06/13)
-
- QUINAZOLINONE DERIVATIVES AND THEIR USE AS B-RAF INHIBITORS
-
The invention relates to chemical compounds of the formula (I): or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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-
Page/Page column 27
(2008/06/13)
-
- QUINOXALINES AS B RAF INHIBITORS
-
The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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Page/Page column 62
(2010/11/08)
-
- 4,6-DISUBSTITUTED PYRIMIDINES AND THEIR USE AS PROTEIN KINASE INHIBITORS
-
The invention relates to novel pyrimidine derivatives of Formula (I), which are efficacious inhibitors of protein kinases, in particular of one or more isoforms of the protein kinase B/Akt.
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-
Page/Page column 56-57
(2008/06/13)
-
- SUBSTITUTED QUINAZOLONES AS ANTI-CANCER AGENTS
-
The invention relates to chemical compounds of the formula (I): or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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Page/Page column 66
(2010/02/15)
-
- SUBSTITUTED PYRIDINONES
-
Disclosed are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and R5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.
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Page/Page column 299
(2008/06/13)
-
- Inhibition of thiamin diphosphate dependent enzymes by 3-deazathiamin diphosphate.
-
3-Deazathiamin diphosphate (deazaTPP) and a second thiamin diphosphate (TPP) analogue having a benzene ring in place of the thiazolium ring have been synthesised. These compounds are both extremely potent inhibitors of pyruvate decarboxylase from Zymomonas mobilis; binding is competitive with TPP and is essentially irreversible even though no covalent linkage is formed. DeazaTPP binds approximately seven-fold faster than TPP and at least 25,000-fold more tightly (K(i) less than 14 pM). DeazaTPP is also a potent inhibitor of the E1 subunit of alpha-ketoglutarate dehydrogenase from E. coli and binds more than 70-fold faster than TPP. In this case slow reversal of the inhibition could be observed and a K(i) value of about 5 nM was calculated (ca. 500-fold tighter binding than TPP).
- Mann, Stephane,Perez Melero, Concepcion,Hawksley, Dan,Leeper, Finian J
-
p. 1732 - 1741
(2007/10/03)
-
- NOVEL BENSOPHENONE DERIVATIVES OR SALTS THEREOF
-
A benzophenone derivative represented by the following formula: whereinR1 represents, for example, an optionally substituted heterocyclic group, or a substituted phenyl group; Z represents, for example, an alkylene group; R2 represents, for example, a carboxyl group optionally protected with alkyl;R3 represents, for example, an optionally protected hydroxyl group; R4 represents, for example, an optionally substituted cycloalkyloxy group; and R5 represents, for example, a hydrogen atom, ???or a salt thereof has anti-arthritic activity, inhibits bone destruction caused by arthritis, and provides high safety and excellent pharmacokinetics and thus is useful as therapeutic agent for arthritis. These compounds have inhibitory effect on AP-1 activity and are useful as preventive or therapeutic agent for diseases in which excessive expression of AP-1 is involved.
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-
-
- Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: Discovery, initial SAR, and molecular modeling
-
The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.
- Colarusso, Stefania,Koch, Uwe,Gerlach, Benjamin,Steinkühler, Christian,De Francesco, Raffaele,Altamura, Sergio,Matassa, Victor G.,Narjes, Frank
-
p. 345 - 348
(2007/10/03)
-
- Hydrazide and alkoxyamide angiogenesis inhibitors
-
Compounds having the formula are methionine aminopeptidase type 2 (MetAP2) inhibitors and are useful for inhibiting angiogenesis. Also disclosed are MetAP2-inhibiting compositions and methods of inhibiting angiogenesis in a mammal.
- -
-
-
- Method for treating glaucoma
-
Methods of using prostaglandin agonists for the reduction of intraocular pressure, and accordingly glaucoma.
- -
-
-
- Prevention of loss and restoration of bone mass by certain prostaglandin agonists
-
Prostaglandin agonists of formula (I), in which, for example, A is a sulphonyl or acyl group, B is N or CH, M contains a ring and K and Q are linking groups, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits useful for the treatment of bone disorders including osteoporosis. STR1
- -
-
-
- 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)
-
- Substituted benzene derivatives useful as neuraminidase inhibitors
-
A compound of the Formula (I): STR1 or pharmaceutically-suitable salts or prodrug forms thereof, wherein: n is 0-1; m is 0; p is 0-1; R1 is --CO2 H; R2 is selected from the group consisting of H, --OH, and --NH2 ; R3 is H; R4 is --C(O)NHR8 ; R5 is --NHC(R6)NH2 R6 is selected from the group consisting of =NH, =NOH, =NCN, =O, and =S; and R8 is selected from the group consisting of C1 -C4 linear or branched alkyl substituted with 0-3 halogens on each carbon.
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-
-
- Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists
-
This invention relates to novel compounds containing basic and acidic termini, pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.
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