Reference_01_08_2014_165529
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40. Direct, nucleophilic radiosynthesis of [18F]trifluoroalkyl tosylates: improved labelling procedures
By Riss, Patrick J.; Ferrari, Valentina; Brichard, Laurent; Burke, Paul; Smith, Robert; Aigbirhio, Franklin I. From Organic & Biomolecular Chemistry (2012), 10(34), 6980-6986. Language: English, Database: CAPLUS, DOI:10.1039/c2ob25802a
A rapid and efficient protocol to afford the title compd. 2-[18F]-fluoro-2,2-difluoroethyl tosylate 18FCF2CH2OTs (I) is described. Starting from [18F]fluoride ion, labeling reagent I was obtained in good yields and a high specific radioactivity. Compd. I was then used to synthesize a prospective radiotracer for PET-imaging in dementia.
~4 Citings
Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.
41. Substituted pyridinylpyrimidines as SYK kinase inhibitors and their preparation and use for the treatment of SYK kinase-mediated diseases
By Dahmann, Georg; Fiegen, Dennis; Fleck, Martin; Hoffmann, Matthias; Klicic, Jasna; East, Stephen Peter; Napier, Spencer Charles R.; Scott, John
From PCT Int. Appl. (2012), WO 2012101013 A1 20120802, Language: English, Database: CAPLUS
The invention relates to pyridinylpyrimidines of formula I, which are SYK kinase inhibitors and which are useful in the treatment of SYK kinase-mediated diseases. Compds. of formula I wherein ring A is (un)substituted (un)satd. 5-membered carbocycle and heterocycle; R1 is H, halo, SH, oxo, etc.; R2 is H, OH, halo, CONH2 and derivs., etc.; R4 and R5 are independently H, F, Cl, Br, etc.; R6 is H, halo, C1-3 alkyl, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compd. II was prepd. by cross-coupling reaction of [4- (4-chloropyridin-2-yl)pyrimidin-2-yl](1,3-dihydroisobenzofuran- 5-yl)amine with (2-aminocarbonylphenyl)boronic acid. All the invention compds. were evaluated for their SYK kinase inhibitory activity. From the assay, it was detd. that compd. II exhibited an IC50 value of 0.015 μM.
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42. Indazole derivatives as sodium channel inhibitors and their preparation and use in the treatment of pain
By Bell, Andrew Simon; De Groot, Marcel John; Lewthwaite, Russell Andrew; Marsh, Ian Roger; Sciammetta, Nunzio; Storer, Robert Ian; Swain, Nigel Alan
From PCT Int. Appl. (2012), WO 2012095781 A1 20120719, Language: English, Database: CAPLUS
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The invention relates to acyl sulfonamide derivs. of formula I, to their use in medicine, to compns. contg. them, to processes for their prepn. and to intermediates used in such processes. The invention relates to a acyl sulfonamide of formula I as Nav1.7 inhibitors that are potentially useful in the treatment of a wide range of disorders, particularly pain. Compds. of formula I wherein R0 and U are independently H and F; V is (un)substituted C1-4 alkyl; W is H, C1-4 alkyl and C3-4 cycloalkyl; X is O, NH and derivs., and absent; Y is H, F and Cl; R1 is H, (un)substituted C1-8 alkyl, (un)substituted C3-8 cycloalkyl, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compd. II was prepd. by etherification of 1-(5-chloro- 6-fluoropyridin-3-yl)-3-methyl-N-methylsulfonyl-1H-indazole-5- carboxamide with 1-methylcyclopropylmethanol. All the invention compds. were evaluated for their sodium channel inhibitory activity. From the assay, it was detd. that compd. II exhibited EIC50 value of 0.08 μM.
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43. sp3 C-H bond functionalization of methyl n-alkyl ketones [MeCOCnH2n+1 (n = 6-8)] as a novel method for the onepot regioselective synthesis of 'bifunctional alkanes' with remote functional groups
By Akhrem, Irena S.; Afanaseva, Lyudmila V.; Kagramanov, Nikolai D.; Petrovskii, Pavel V. From Tetrahedron Letters (2012), 53(32), 4221-4224. Language: English, Database: CAPLUS, DOI:10.1016/j.tetlet.2012.05.164
Selective one-pot functionalization of Me n-alkyl ketones, CnH2n+1COMe (n = 6-8) involving C-sp3-H bond cleavage with CO and various nucleophilic substrates [iPrOH, BuCH(Et)CH2OH, CF3CH2OH, (CF3)(Me)CHOH, H(CF2)2CH2OH,
HCCCH2OH, furan, thiophene, and anisole] in the presence of the superelectrophilic system CBr4·2AlBr3 has been performed for the first time.
~2 Citings
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44. Preparation of oxime compounds as HDL-cholesterol raising agents
By Hebeisen, Paul; Roever, Stephan
From PCT Int. Appl. (2012), WO 2012080144 A1 20120621, Language: English, Database: CAPLUS
The invention relates to compds. oximes of formula I and their pharmaceutically acceptable salts as HDL-cholesterol raising agents; their prepn. and use in the treatment of dyslipidemia, atherosclerosis and cardiovascular diseases. Compds. of formula I wherein A1, A2 and A3 are N and CH, provided that at least one of A1, A2 or A3 is N and at least one of A1, A2 and A3 is CH; R1 is lower alkyl, cycloalkyl, hydroxyalkyl, haloalkyl, carbamoylalkyl, etc.; R2 and R6 are independently H and halo; R3 and R5 are independently H, lower (halo)alkyl, lower alkoxy, halo, cyano, etc.; R4 is H, halo, cyano, etc.; R7 is H; R8 is lower cycloalkyl and haloalkyl; R7 and R8 together form cycloalkyl; R9 is H, lower (halo)alkyl, alkoxyalkyl and carbamoylalkyl; and their pharmaceutically acceptable salts, are claimed. Example compd. II was prepd. by oxidn. of 5-(4-chlorophenyl)-6- cyclopropylmethoxy-N-((1S,2R)-2- hydroxycyclohexyl)nicotinamide followed by condensation of the resulting 5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((S)-2- oxocyclohexyl)nicotinamide with O-methylhydroxylamine hydrochloride. All the invention compds. were evaluated for their ABCA1 protein increasing efficacy. From the assay it was detd. that example compd. II exhibited 87.2 % at 3μM and EC50 value of 0.7 μM.
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45. Purification of optically-active 1,1,1-trifluoro-2-propanol via its arylmethyl ether
By Ishii, Akihiro; Otsuka, Takashi
From Jpn. Kokai Tokkyo Koho (2012), JP 2012102032 A 20120531, Language: Japanese, Database: CAPLUS
Optically-active CF3CHMeOH (I), useful as a drug intermediate, is purified by reacting a mixt. contg. (R)- or (S)-I and C1-4 alcs. with XCH2Ar [Ar = (un)substituted aryl; X = halo] in the presence of bases to selectively prep. (R)- or (S)- ArCH2OCHMeCF3 and dearalkylating the ethers. Thus, PhCH2Br was added dropwise to a mixt. of toluene, (S)-I (98.8% e.e.), prepd. by bacterial conversion from 1,1,1-trifluoroacetone (II) with Hansenula polymorpha, EtOH, an aq. KOH soln., H2O, and Bu4NBr and the mixt. was stirred at 30° for 3 h to give crude product contg. (S)-I benzyl ether (III). The crude product was combined with another crude product prepd. similarly by the above method and the mixt. was subjected to fractional distn. to give III contg. 0.02% EtOH. The purified III was autoclaved with H in hexanol at 35° overnight and subjected to fractional distn. to give (S)-I contg. neither EtOH nor II.
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46. Electropolymerized and polymer grafted superhydrophobic, superoleophilic, and hemi-wicking coatings
By Foster, Edward L.; De Leon, Al Christopher C.; Mangadlao, Joey; Advincula, Rigoberto
From Journal of Materials Chemistry (2012), 22(22), 11025-11031. Language: English, Database: CAPLUS, DOI:10.1039/c2jm31067h
A novel one step approach to fabricate superhydrophobic and superoleophilic electrodeposited coatings is reported. By performing addnl. surface-initiated atom transfer radical polymn. (SI-ATRP) from the coating, a further change in wettability of the substrates to a variety of liqs. was obsd.
~5 Citings
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47. Preparation of pyrrolidine derivatives as cathepsin inhibitors
By Banner, David; Grether, Uwe; Haap, Wolfgang; Kuehne, Holger; Mauser, Harald; Plancher, Jean-Marc From PCT Int. Appl. (2012), WO 2012059507 A1 20120510, Language: English, Database: CAPLUS
The invention relates to pyrrolidine derivs. of formula I as cathepsin inhibitors and their methods for prepn. Compds. of formula I wherein R1 is H, alkyl, morpholinyl, (halo)alkylamino, etc.; R2 - R6 are independently H, (halo)alkyl, hydroxyalkyl, (halo)alkoxy, halo, etc.; A1 is CH2, CO, CO2, and absent; A2 is N and CR7; A3 is N and CR8; A4 is N and CR9; R7 is H, (halo)alkyl, halo, etc.; R8 is H, (halo)alkyl, halo, and OH; R9 is H, (halo)alkyl, halo, and NO2; R7R8 can be taken together to form cycloalkyl or substituted pyrrolidine; R8R9 can be taken together to form cycloalkyl; or pharmaceutically acceptable salts, are claimed. Example compd. II was prepd. by sulfonylation of (2S,4R)-4-hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-Bu 2-Me ester with 3-nitrobenzenesulfonyl chloride; the resulting (2S,4R)-4-(3-nitrobenzenesulfonyloxy)pyrrolidine- 1,2-dicarboxylic acid 1-tert-Bu 2-Me ester underwent nucleophilic substitution with 2-chlorothiophenol to give (2S,4S)-4-(2-chlorophenylsulfanyl)pyrrolidine-1,2-dicarboxylic acid 1-tert-Bu 2-Me ester, which underwent oxidn. to give (2S,4S)-4-(2-chlorophenylsulfonyl)pyrrolidine-1,2-dicarboxylic acid 1-tert-Bu 2-Me ester, which underwent hydrolysis to give the corresponding pyrrolidine-1,2-dicarboxylic acid 1-tert-Bu ester, which underwent amidation with morpholine and Bocdeprotection to give compd. II. Invention compds. were evaluated for their cathepsin inhibitory activity. From the assay, it was detd. that compd. II exhibited IC50 value of 0.415 μM for Cathepsin S.
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48. Preparation of arylamide derivatives as tetrodotoxin-sensitive (TTX-S) blockers
By Yamagishi, Tatsuya; Kawamura, Kiyoshi; Arano, Yoshimasa; Morita, Mikio
From PCT Int. Appl. (2012), WO 2012053186 A1 20120426, Language: English, Database: CAPLUS
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Title compds. I [R1 = CF3, CHF2, OCF3, OCHF2, OCH2CHF2, etc.; R2 independently = H, halo, OH, (un)substituted alkyl, cycloalkyl, etc.; p = 1-4; R3 and R4 independently = H or (un)substituted alkyl; X = C or N; Y = H or alkyl; Ar = (un)substituted aryl], and their pharmaceutically acceptable salts, prodrugs, or solvates, are prepd. and disclosed. Thus, e.g., II was prepd. by acylation of 1-[5-methyl-6-(2,2,2- trifluoroethoxy)pyridin-3-yl]ethanamine with 2-aminopyrimidine- 4-carboxylic acid followed by condensation reaction with propionyl chloride. II exhibited IC50 value of < 1 μM against Nav1.3 and Nav1.7, resp. The invention compds. have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved.
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49. Preparation of N-pyridinylcarboxamide derivatives and analogs for use as HDL-cholesterol raising agents
By Grether, Uwe; Hebeisen, Paul; Hoffmann, Torsten; Roever, Stephan
From PCT Int. Appl. (2012), WO 2012049190 A1 20120419, Language: English, Database: CAPLUS
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Title compds. I [A = CH or N; R1 = alkyl, cycloalkyl, (un)substituted Ph, etc.; R2 and R6 independently = H or halo; R3 and R5 independently = H, alkyl, halo, CN, etc.; R4 = H, alkyl, alkoxy, halo, etc.; R7 = alkyl, (un)substituted cycloalkyl, Ph, etc.], and their pharmaceutically acceptable salts, are prepd. and disclosed as HDL-cholesterol raising agents. Thus, e.g., II was prepd. by etherification of 3-bromo-2-chloro-5- nitropyridine with 2,2,2-trifluoroethanol followed by redn., coupling with 4-chlorophenylboronic acid, and condensation with valeric acid. I were evaluated in CB1 and CB2 receptor affinity assays, e.g., II demonstrated a percent inhibition at 10 μM of 45% and 9.2%, resp.
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50. A new entry for the oxidation of fluoroalkyl-substituted methanol derivatives: Scope and limitation of the organoiodine(V) reagent-catalyzed oxidation
By Tanaka, Yusuke; Ishihara, Takashi; Konno, Tsutomu
From Journal of Fluorine Chemistry (2012), 137, 99-104. Language: English, Database: CAPLUS, DOI:10.1016/j.jfluchem.2012.03.002
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Oxidn. of various fluoroalkyl-substituted methanol derivs. under the influence of a catalytic amt. of sodium 2- iodobenzenesulfonate and oxone in CH3CN or CH3NO2 was investigated in detail. The efficiency of the newly developed oxidn. was also evaluated by comparison to other oxidns., such as Dess-Martin, PDC, and Swern oxidn.
~4 Citings
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51. A Self-Immolative Spacer That Enables Tunable Controlled Release of Phenols under Neutral Conditions
By Schmid, Kyle M.; Jensen, Lasse; Phillips, Scott T.
From Journal of Organic Chemistry (2012), 77(9), 4363-4374. Language: English, Database: CAPLUS, DOI:10.1021/jo300400q
A current challenge in the area of responsive materials is the design of reagents and polymers that provide controlled release of phenols in environments that are less polar than water. In these contexts, a mol. strategy that enables release of nearly any phenol with predictable and tunable rates and without complication from background hydrolysis would substantially increase the precision with which materials can be designed to respond to a particular signal. This Article addresses this problem at the fundamental level by describing the design, synthesis, and phys.-org. characterization of two small mol. self-immolative spacers that are capable of releasing phenols in org. and mixed org.-aq. solns. The rate of release from these small mol. model systems is predictable and tunable, such that nearly any type of phenol, regardless of pKa value, can be released in neutral solns. without complications from nonspecific background release due to hydrolysis. Furthermore, the release properties of the spacers can be predicted from bond length and conformation data (obtained from crystal structures). On the basis of these results, it should now be possible to incorporate these design elements into materials to enable precise response properties in environments that are not 100% aq.
~10 Citings
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52. Pyrazolopyridines as inhibitors of the kinase LRRK2 and their preparation and use in the treatment of cancer and neurodegenerative diseases
By Chan, Bryan; Chen, Huifen; Estrada, Anthony; Shore, Daniel; Sweeney, Zachary; McIver, Edward From PCT Int. Appl. (2012), WO 2012038743 A1 20120329, Language: English, Database: CAPLUS
The invention relates to pyrazolopyrimidine compds. or pharmaceutically acceptable salts or esters thereof, as LRRK2 inhibitors. Further aspects relate to pharmaceutical compns. and therapeutic uses of said compds. Example compd. I was prepd. by amidation of 3-[4-(tetrahydro-2H_pyran-4-ylamino)- 1H_pyrazolo[4,3-c]pyridin-3-yl]propanoic acid with (R)-3- phenylpiperidine. All the invention compds. were evaluated for their LRRK2 inhibitory activity (some data given).