cas 150529-73-0, (3-BROMOPHENYL)ACETIC ACID METHYL ESTER

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Lipase-catalyzed chemoselective ester hydrolysis of biomimetically coupled aryls for the synthesis of unsymmetric biphenyl esters
Lipases are among the most frequently used biocatalysts in organic synthesis, allowing numerous environmentally friendly and inexpensive chemical transformations. Here, we present a biomimetic strategy based on iron(III)-catalyzed oxidative coupling and s
Ehlert, Janna,Kronemann, Jenny,Zumbr?gel, Nadine,Preller, Matthias
(2019)
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B(C6F5)3-catalyzed O-H insertion reactions of diazoalkanes with phosphinic acids
A highly efficient base-, metal-, and oxidant-free catalytic O-H insertion reaction of diazoalkanes and phosphinic acids in the presence of B(C6F5)3has been developed. This powerful methodology provides a green approach towards the synthesis of a broad spectrum of α-phosphoryloxy carbonyl compounds with good to excellent yields (up to 99% yield). The protocol features the advantages of operational simplicity, high atom economy, practicality, easy scalability and environmental friendliness.
Jiang, Jun,Zhang, Xinzhi,Zhang, Yangyang,Zhao, Jincheng
supporting information
p. 5772 - 5776
(2021/07/12)

B(C6F5)3-Catalyzed site-selective N1-alkylation of benzotriazoles with diazoalkanes
Alkylation of benzotriazoles is synthetically challenging, often leading to mixtures of N1 and N2 alkylation. Herein, metal-free catalytic site-selective N1-alkylation of benzotriazoles with diazoalkanes is described in the presence of 10 mol% of B(C6F5)3. These reactions provide N1-alkylated benzotriazoles in good to excellent yields and this protocol is successfully adapted to gram-scale syntheses as well as a derivative with antimicrobial activity.
Guo, Jing,Mandal, Dipendu,Stephan, Douglas W.,Wu, Yile,Zhao, Yunbo
supporting information
p. 7758 - 7761
(2021/08/13)

Pyridineacetamide derivative serving as CDK inhibitor, and preparation method and application thereof
The invention belongs to the technical field of pyridineacetamide derivatives, and particularly relates to a pyridineacetamide derivative serving as a CDK inhibitor and a preparation method and application of the pyridine acetamide derivative. The pyridineacetamide derivative shows excellent CDK9/CDK7 enzyme inhibitory activity, and can be used for preparing drugs used for treating cancers, especially hematologic cancers including acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, follicular lymphoma and the like and solid tumors such as breast cancer, prostate cancer, ovarian cancer, hepatocellular carcinoma, pancreatic cancer, kidney cancer, stomach cancer, colorectal cancer, lung cancer and the like.
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Paragraph 0214-0219

(2021/07/28)

Photocatalytic Hydromethylation and Hydroalkylation of Olefins Enabled by Titanium Dioxide Mediated Decarboxylation
A versatile method for the hydromethylation and hydroalkylation of alkenes at room temperature is achieved by using the photooxidative redox capacity of the valence band of anatase titanium dioxide (TiO2). Mechanistic studies support a radical-based mechanism involving the photoexcitation of TiO2 with 390 nm light in the presence of acetic acid and other carboxylic acids to generate methyl and alkyl radicals, respectively, without the need for stoichiometric base. This protocol is accepting of a broad scope of alkene and carboxylic acids, including challenging ones that produce highly reactive primary alkyl radicals and those containing functional groups that are susceptible to nucleophilic substitution such as alkyl halides. This methodology highlights the utility of using heterogeneous semiconductor photocatalysts such as TiO2 for promoting challenging organic syntheses that rely on highly reactive intermediates.
Zhu, Qilei,Nocera, Daniel G.
supporting information
p. 17913 - 17918
(2020/12/04)

Efficient Synthesis of Spirooxindole Pyrrolones by a Rhodium(III)-Catalyzed C?H Activation/Carbene Insertion/Lossen Rearrangement Sequence
A rhodium(III)-catalyzed domino annulation of simple olefins with diazo oxindoles to give spirooxindole pyrrolone products is described. This reaction can be formally viewed as the result of an anomalous tandem C?H activation, carbene insertion, Lossen rearrangement, and a nucleophilic addition process. The potential utility of this reaction was further demonstrated by the late-stage diversification of drug molecules.
Ma, Biao,Wu, Peng,Wang, Xing,Wang, Zhengyu,Lin, Hai-Xia,Dai, Hui-Xiong
supporting information
p. 13335 - 13339
(2019/08/20)

Conformationally rigid derivatives of WAY-267,464: Synthesis and pharmacology at the human oxytocin and vasopressin-1a receptors
WAY-267,464 (1) and twelve conformationally rigid analogues (3a-f–4a-f) were synthesised, characterised and evaluated in cellular assays with the aim of systematically exploring interactions with the oxytocin receptor (OTR). Each analogue was evaluated in
Jorgensen, William T.,Gulliver, Damien W.,Katte, Timothy A.,Werry, Eryn L.,Reekie, Tristan A.,Connor, Mark,Kassiou, Michael
p. 1644 - 1656
(2017/11/13)

Photochemical intramolecular amination for the synthesis of heterocycles
Polycyclic heterocycles can be formed in good to excellent yields via photochemical conversion of the corresponding substituted aryl azides under irradiation with purple LEDs in a continuous flow reactor. The experimental set-up is tolerant to UV-sensitive functional groups while affording diverse carbazoles, as well as an indole and pyrrole framework, in short reaction times. The photochemical method is presumed to progress through a mechanism differing from the other methods of azide activation involving transition metal catalysis.
Parisien-Collette, Shawn,Cruché, Corentin,Abel-Snape, Xavier,Collins, Shawn K.
supporting information
p. 4798 - 4803
(2017/10/23)

CHEMICAL COMPOUNDS ACTING AS PERK INHIBITORS
The invention is directed to substituted pyrrolidinone derivatives. Specifically, the invention is directed to compounds according to Formula X: wherein R41, R42, R43, R44, R45, R46, and R47 are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt- Jakob Disease, and related prion diseases, amyotrophic lateral sclerosis, myocardial infarction, neurodegeneration, cardiovascular disease, atherosclerosis, ocular diseases, and arrhythmias, more specifically cancers of the breast, colon, pancreas and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 123

(2015/10/05)

Acetylcholinesterase inhibition activity of some quinolinyl substituted triazolothiadiazole derivatives
A series of aralkanoic acids was converted into aralkanoic acid hydrazides through their esters formation. The aralkanoic acid hydrazides upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazinate salts, which on refluxing with aqueous hydrazine hydrate yielded 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles. The target compounds, 3-aralkyl-6-(substitutedquinolinyl) [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, were synthesized by condensing various quinolinyl substituted carboxylic acids with 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles in phosphorus oxychloride. The structures of the newly synthesized triazolothiadiazoles were characterized by IR, 1H NMR, 13C NMR, and elemental analysis studies. The structure of one of the 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles was unambiguously deduced by single crystal X-ray diffraction analysis. All the synthesized compounds were screened for their acetylcholinesterase inhibition activities. Four of the triazolothiadiazoles exhibited excellent acetylcholinesterase inhibition activities as compared to the reference inhibitor.
Rafiq, Muhammad,Saleem, Muhammad,Hanif, Muhammad,Abbas, Qamar,Lee, Ki Hwan,Seo, Sung-Yum
p. 170 - 177
(2015/04/14)

BIARYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PHARMACEUTICALS
The present invention relates to compounds of the formula (I), wherein X, R, R1, R2, D, E1, E2, E3, E4, G1, G2, G3 and G4 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease ca
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Page/Page column 80

(2014/10/15)

BIARYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PHARMACEUTICALS
The present invention relates to compounds of the formula (I), wherein X, R, R1, R2, D, E1, E2, E3, E4, G1, G2, G3 and G4 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease ca
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Page/Page column 84

(2014/10/15)

MACROCYCLIC FACTOR VIIA INHIBITORS
The present invention provides compounds of Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.
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Paragraph 00225

(2015/01/09)

NOVEL MOLECULES THAT SELECTIVELY INHIBIT HISTONE DEACETYLASE 6 RELATIVE TO HISTONE DEACETYLASE 1
The compounds of the present invention are HDAC6 selective inhibitors which are identified on the basis of accumulation of acetylated tubulin without accumulation of acetylated histones. Histone deacetylase or "HDAC" refers to enzymes capable of cleaving an acetyl group (-C(=0)CH3) from proteins, including histone and microtubulins. Compositions comprising the molecules and methods for their use to inhibit the activity of histone deacetylase, including for treatment, are also disclosed.
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Page/Page column 63; 64

(2013/04/24)

ANTIVIRAL COMPOUNDS
The present invention relates to a compound of formula: (I) or a pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing a viral infection such as HIV using the same.
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Paragraph 0180

(2013/03/26)

Switching pathways: Room-temperature neutral solvolysis and substitution of amides
Stick or twist: By introducing steric hindrance at the nitrogen atom, stable linear amides bearing an electron-withdrawing α-substituent (Z=Ar, PhSO2, P(O)(OR)2, CN, or CO2R) can be induced to undergo solvolysis and substitution reactions through an elimination-addition mechanism (see picture). Key to this process is a low barrier to rotation around the amide bond and the α-substituentZ. Copyright
Hutchby, Marc,Houlden, Chris E.,Haddow, Mairi F.,Tyler, Simon N. G.,Lloyd-Jones, Guy C.,Booker-Milburn, Kevin I.
supporting information; experimental part
p. 548 - 551
(2012/02/04)

Ene reductase-catalysed synthesis of (R)-profen derivatives
Enantiomerically pure (R)-profen derivatives and intermediates are synthesised utilising the enzyme YqjM, an ene reductase from Bacillus subtilis. After optimisation of the reaction conditions, the chemoenzymatic approach was applied for the first time in the synthesis of (R)-flurbiprofen methyl ester. Copyright
Pietruszka, Joerg,Schoelzel, Melanie
scheme or table
p. 751 - 756
(2012/04/23)

COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I.1, Formula I.2, Formula IA, Formula IB, Formula IC and Formula II and their pharmaceutical acceptable salts for the treatment of cancer. The use of
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Page/Page column 31-32

(2012/08/07)

3-(3-Pyrimidine-2-yl-benzyl)-[1,2,4] triazolo[4,3-b]pyrimidine derivatives
Compounds of the formula I, in which R1, R2, R3, R3, R4 have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the t
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Page/Page column 19

(2011/10/31)

3 (3-Pyrimidin-2-ylbenzyl)-1,2,4-triazolo[4,3-b]pyridazine derivatives
Compounds of the formula (I), in which R1, R2, R3, R3′, R4 have the meanings indicated in claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for th
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Page/Page column 19-20

(2011/10/31)

Rational design of phosphoinositide 3-kinase inhibitors that exhibit selectivity over the phosphoinositide 3-kinase isoform
Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3K has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K vs PI3K selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K that is not attained with the corresponding Lys777 of PI3K. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.
Heffron, Timothy P.,Wei, Binqing,Olivero, Alan,Staben, Steven T.,Tsui, Vickie,Do, Steven,Dotson, Jennafer,Folkes, Adrian J.,Goldsmith, Paul,Goldsmith, Richard,Gunzner, Janet,Lesnick, John,Lewis, Cristina,Mathieu, Simon,Nonomiya, Jim,Shuttleworth, Stephen,Sutherlin, Daniel P.,Wan, Nan Chi,Wang, Shumei,Wiesmann, Christian,Zhu, Bing-Yan
experimental part
p. 7815 - 7833
(2012/01/05)

Synthesis and biological evaluation of loxoprofen derivatives
Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory actions through an inhibitory effect on cyclooxygenase (COX). Two COX subtypes, COX-1 and COX-2, are responsible for the majority of COX activity at the gastrointestinal mucosa and in tissues with inflammation, respectively. We previously suggested that both gastric mucosal cell death due to the membrane permeabilization activity of NSAIDs and COX-inhibition at the gastric mucosa are involved in NSAID-induced gastric lesions. We have also reported that loxoprofen has the lowest membrane permeabilization activity among the NSAIDs we tested. In this study, we synthesized a series of loxoprofen derivatives and examined their membrane permeabilization activities and inhibitory effects on COX-1 and COX-2. Among these derivatives, 2-{4′-hydroxy-5-[(2-oxocyclopentyl)methyl]biphenyl-2-yl}propanoate 31 has a specificity for COX-2 over COX-1. Compared to loxoprofen, oral administration of 31 to rats produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 31 is likely to be a therapeutically beneficial and safer NSAID.
Yamakawa, Naoki,Suemasu, Shintaro,Matoyama, Masaaki,Tanaka, Ken-Ichiro,Katsu, Takashi,Miyata, Keishi,Okamoto, Yoshinari,Otsuka, Masami,Mizushima, Tohru
experimental part
p. 3299 - 3311
(2011/07/08)

Discovery of orally available 8-aza-5-thiaProstaglandin E1 analogs as highly selective EP4 agonists
Analogs 8-aza-16-aryl prostaglandin E1 (PGE1) and 8-aza-5-thia-16-arylPGE1 were synthesized and evaluated with respect to their subtype receptor affinity and EP4 agonist activity for the purposes of identifying sub-type- selective EP
Kambe, Tohru,Maruyama, Toru,Nakano, Masayuki,Yamaura, Yoshiyuki,Shono, Tomoyuki,Seki, Akiteru,Sakata, Kiyoto,Maruyama, Takayuki,Nakai, Hisao,Toda, Masaaki
experimental part
p. 1523 - 1534
(2012/01/13)

FUSED PYRAZINE DERIVATIVES AS KINASE INHIBITORS
A series of quinoxaline derivatives, and analogues thereof, which are functionalised further by a substituted phenyl or pyridinyl moiety, being selective inhibitors of PO kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions.
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Page/Page column 36

(2010/06/11)

4-AMINO-7,8-DIHYDROPYRIDO[4,3-d]PYRIMIDIN-5(6H)-ONE DERIVATIVES
The invention provides compounds of the general Formula (I) where R1, R2, and A are defined herein, as well as the preparation, compositions and uses thereof.
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Page/Page column 15

(2010/08/08)

DIAMIDE COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND β2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
This invention relates to a compound of formula I; or a pharmaceutically acceptable salt thereof. Such compounds possess both muscarinic receptor antagonist and β2 adrenergic receptor agonist activities. The invention also relates to pharmaceutical compositions comprising such compounds, processes and intermediates for preparing such compounds, and methods of using such compounds as bronchodilating agents to treat pulmonary disorders.
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Page/Page column 62

(2010/11/05)

SUBSTITUTED AROMATIC COMPOUNDS AND PHARMACEUTICAL USES THEREOF
The present invention relates to substituted aromatic compounds of Formula (I) and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds in the prevention and/or treatment of various diseases and conditions in subjects, including the prevention or treatment of (i) blood disorders, (ii) renal disorders, nephropathies, or renal disorder complications; (iii) inflammatory-related diseases; and/or (iv) oxidative stress related disorders.
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Page/Page column 45

(2010/11/18)

Identification of novel urease inhibitors by high-throughput virtual and in vitro screening
Ureases are important in both agriculture and human health. Bacterial ureases are directly involved in many farm-field problems and pathological conditions. Here, we report a structure-based virtual screening of an in-house compound bank of about 6000 molecular entities by computational docking and binding free energy calculations followed by in vitro screening. Applied protocol leads to the identification of novel urease inhibitors, which can serve as starting points for structural optimization.
Abid, Obaid-Ur-Rahman,Babar, Tariq Mahmood,Ali, Farukh Iftakhar,Ahmed, Shahzad,Wadood, Abdul,Rama, Nasim Hasan,Uddin, Reaz,Zaheer-Ul-Haq,Khan, Ajmal,Choudhary, M. Iqbal
scheme or table
p. 145 - 149
(2010/10/19)

Inhalation by design: Novel ultra-long-acting β2- adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup
A novel series of potent and selective sulfonamide derived β2-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.
Glossop, Paul A.,Lane, Charlotte A. L.,Price, David A.,Bunnage, Mark E.,Lewthwaite, Russell A.,James, Kim,Brown, Alan D.,Yeadon, Michael,Perros-Huguet, Christelle,Trevethick, Michael A.,Clarke, Nicholas P.,Webster, Robert,Jones, Rhys M.,Burrows, Jane L.,Feeder, Neil,Taylor, Stefan C. J.,Spence, Fiona J.
scheme or table
p. 6640 - 6652
(2010/11/19)

N,N-DISUBSTITUTED AMINOALKYLBIPHENYL ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
Described herein are compounds that are antagonists of PGD2 receptors. Also described are pharmaceutical compositions that include the compounds described herein, and methods of using such antagonists of PGD2 receptors, alone or in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2-mediated conditions or diseases.
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Page/Page column 17; 18

(2009/08/16)

ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
Described herein are compounds that are antagonists of PGD2 receptors. Also described are pharmaceutical compositions and medicaments that include the antagonists of PGD2 receptors described herein, as well as methods of using such a
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Page/Page column 124

(2009/10/21)

NOVEL ADENINE COMPOUND
An adenine compound useful for a medicament represented by the following formula (1): , wherein A1 and A2 are independently, optionally substituted cyclic aromatic hydrocarbon group or optionally substituted aromatic heterocyclic gro
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Page/Page column 41

(2008/12/06)

Identification of (R)-1-(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H- indazol-4-yl)urea (ABT-102) as a potent TRPV1 antagonist for pain management
Vanilloid receptor TRPV1 is a cation channel that can be activated by a wide range of noxious stimuli, including capsaicin, acid, and heat. Blockade of TRPV1 activation by selective antagonists is under investigation by several pharmaceutical companies in an effort to identify novel agents for pain management. Here we report that replacement of substituted benzyl groups by an indan rigid moiety in a previously described N-indazole-N′-benzyl urea series led to a number of TRPV1 antagonists with significantly increased in vitro potency and enhanced drug-like properties. Extensive evaluation of pharmacological, pharmacokinetic, and toxicological properties of synthesized analogs resulted in identification of (R)-7 (ABT-102). Both the analgesic activity and drug-like properties of (R)-7 support its advancement into clinical pain trials.
Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Surowy, Carol S.,Honore, Prisca,Marsh, Kennan C.,Hannick, Steven M.,McDonald, Heath A.,Wetter, Jill M.,Sullivan, James P.,Jarvis, Michael F.,Faltynek, Connie R.,Lee, Chih-Hung
p. 392 - 395
(2008/09/17)

A COMBINATION OF NIACIN AND A PROSTAGLANDIN D2 RECEPTOR ANTAGONIST
The present invention is directed to a pharmaceutical composition comprising Niacin or a pharmaceutically acceptable salt, solvate or N-oxide thereof, or a nicotinic acid receptor agonist, and a compound of formula (I) as defined herein, or an N-oxide thereof, or an ester prodrug thereof, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, and its use for treating atherosclerosis, dyslipidemia, diabetes or a related condition while reducing substantial flushing.
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Page/Page column 201

(2008/06/13)

Phenylglycinamide and pyridylglycinamide derivatives useful as anticoagulants
The present invention provides novel phenylglycinamide derivatives of Formula (I) or (IV): or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein the variables W, W1, Y, Z, R7, R8, R9, and R11 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.
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Page/Page column 96

(2010/11/25)

Synthesis and biological evaluation of benzoic acid derivatives as potent, orally active VLA-4 antagonists
A series of benzoic acid derivatives was synthesized as VLA-4 antagonists. Introduction of chlorine or bromine into the 3-position on the central benzene of the diphenylurea portion as in lead compound 2 led to improvement in the pharmacokinetic properties. In particular, 12l demonstrated an acceptable plasma clearance and bioavailability in mice and rats as well as dogs (mice, CL = 18.5 ml/min/kg, F = 28 %; rats, CL = 5.2 ml/min/kg, F = 36 %; dogs, CL = 3.6 ml/min/kg, F = 55 %). Additionally, 12l exhibited potent activity with an IC50 value of 0.51 nM and efficacy by oral administration at a dosage of 10 mg/kg in a rat pleurisy model.
Chiba, Jun,Iimura, Shin,Yoneda, Yoshiyuki,Watanabe, Toshiyuki,Muro, Fumito,Tsubokawa, Masao,Iigou, Yutaka,Satoh, Atsushi,Takayama, Gensuke,Yokoyama, Mika,Takashi, Tohru,Nakayama, Atsushi,Machinaga, Nobuo
p. 1679 - 1693
(2008/02/03)

COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS
The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) fam
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Page/Page column 17-18

(2008/06/13)

SPIRO IMIDAZOLE DERIVATIVES AS PPAR MODULATORS
The invention provides compounds (Ia), (Ib) and (Ic), pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated
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Page/Page column 34; 35

(2008/06/13)

BEZOTHIAZOL DERIVATIVES AS BETA2 ADRENORECEPTOR AGONISTS
The present invention relates to compounds according to formula (I) , a process for preparing them, the intermediate compounds of the process and the use of the compounds in the manufacture of a medicament for use in treating diseases such as ARDS, pulmonary emphysema, bronchitis, bronchiectasis, COPD, asthma and rhinitis. The compounds are beta2 adrenoreceptor agonists.
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Page/Page column 86

(2008/06/13)

2, 6-SUBSTITUTED-4-MONOSUBSTITUTEDAMINO-PYRIDIMIDINE AS PROSTAGLANDIN D2 RECEPTOR ANTAGONISTS
The present invention is directed a compound of Formula (I) as defined herein, a pharmaceutical composition comprising a pharmaceutically effective amount of one or more compounds according to Formula (I) in admixture with a pharmaceutically acceptable carrier, and a method of treating a patient suffering from a PGD2-mediated disorder including, but not limited to, allergic disease (such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, discorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, bronchitis, urticaria, eczema, diseases accompanied by itch (such as atopic dermatitis and urticaria), diseases (such as cataract, retinal detachment, inflammation, infection and sleeping disorders) which is generated secondarily as a result of behavior accompanied by itch (such as scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis and the like by administering to said patient a pharmaceutically effective amount of a compound according to Formula (I).
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Page/Page column 202

(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 80

(2008/06/13)

COMPOUNDS FOR THE TREATMENT OF DISEASES
The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in
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Page/Page column 46

(2008/06/13)

L-tartrate salt of N-1-Adamantyl-2-{3-[(2R)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)propyl] phenyl}acetamide
This invention relates to the L-tartrate salt of N-1-Adamantyl-2-{3-[(2R)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)propyl]phenyl}acetamide and its use as a medicament.
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Page/Page column 9

(2008/06/13)

Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme
The present invention relates to compounds that are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome and other diseases and conditions that are mediated by excessive glucocorticoid action.
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Page/Page column 37

(2008/06/13)

Modulators of LXR
Compounds of the invention, such as compounds of formula (I): where n, m, A, B, R1, R2, R3, R4 and R5 are defined herein, are useful as modulators of the activity of liver X receptors. Pharmaceutical compositions containing the compounds and methods of using the compounds are also disclosed.
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(2008/06/13)

The diazo route to diazonamide A. Studies on the indole bis-oxazole fragment
Various approaches to the indole bis-oxazole fragment of the marine secondary metabolite diazonamide A are described, all of which feature dirhodium(II)-catalyzed reactions of diazocarbonyl compounds in key steps. Thus, 3-bromophenylacetaldehyde is conver
Davies, James R.,Kane, Peter D.,Moody, Christopher J.
p. 7305 - 7316
(2007/10/03)

BENZOFURAN DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS
The invention relates to novel heterocycles of formula (I), processes for their preparation and their use for preparing medicaments for the treatment or prophylaxis of disorders, especially of hyperproliferative disorders.
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Page/Page column 83

(2008/06/13)

Design, synthesis, and biological evaluation of N-acetyl-2-(or 3-)carboxymethylbenzenesulfonamides as cyclooxygenase isozyme inhibitors
A group of N-acetyl-2-(or 3-)carboxymethylbenzenesulfonamides, possessing either a F or a substituted-phenyl ring substituent (4-F, 2,4-F2, 4-SO2Me, 4-OCHMe2) attached to its C-4 or C-6 position, was prepared using a palladium-catalyzed Suzuki cross-coupling reaction for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. Although N-acetyl-3-carboxymethyl-6-fluorobenzenesulfonamide [14, COX-1 IC50 = 2.26 μM; COX-2 IC50 = 0.012 μM; COX-2 selectivity index (SI) = 188] and N-acetyl-3-carboxymethyl-6-(4-isopropoxyphenyl)benzenesulfonamide (20c, COX-1 IC50 >100 μM; COX-2 IC50 = 0.15 μM; COX-2 SI >667) exhibited potent in vitro COX-2 inhibitory activity and high COX-2 selectivity, both compounds were inactive anti-inflammatory agents in a carrageenan-induced rat paw edema assay. In contrast, the less potent and less selective COX-2 inhibitors N-acetyl-2-carboxymethyl-4-fluorobenzenesulfonamide (12, COX-1 IC50 = 4.25 μM; COX-2 IC50 = 0.978 μM; COX-2 SI = 4.3), N-acetyl-2-carboxymethyl-4-(2,4-difluorophenyl) benzenesulfonamide (17c, COX-1 IC50 = 1.02 μM; COX-2 IC 50 = 1.00 μM; COX-2 SI = 1.02), and N-acetyl-3-carboxymethyl-6-(4- methanesulfonylphenyl)benzenesulfonamide (20e, COX-1 IC50 = 0.109 μM; COX-2 IC50 = 1.14 μM; COX-2 SI = 0.095) exhibited moderate anti-inflammatory activity where a 75 mg/kg oral dose reduced inflammation 26%, 14%, and 20%, respectively, at 3 h postdrug administration relative to the reference drug aspirin where a 50 mg/kg oral dose reduced inflammation by 25% at 3 h postdrug administration.
Chen, Qiao-Hong,Rao, P. N. Praveen,Knaus, Edward E.
p. 4694 - 4703
(2007/10/03)

Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity
Some κ opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 μM) while displaying high affinity toward the cloned human κ opioid receptor, good κ/δ and κ/μ selectivity, and potent in vitro and in vivo agonist activity.
Le Bourdonnec, Bertrand,Ajello, Christopher W.,Seida, Pamela R.,Susnow, Roberta G.,Cassel, Joel A.,Belanger, Serge,Stabley, Gabriel J.,DeHaven, Robert N.,DeHaven-Hudkins, Diane L.,Dolle, Roland E.
p. 2647 - 2652
(2007/10/03)

Quinolinone derivatives, pharmaceutical compositions containing them and their use
The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in
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(2008/06/13)