- Chiral Primary Amine Catalyzed Enantioselective Tandem Reactions Based on Heyns Rearrangement: Synthesis of α-Tertiary Amino Ketones
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Herein, we disclose a new catalytic asymmetric tandem reaction based on the Heyns rearrangement for the synthesis of chiral α-amino ketones with readily available substrates. The rearrangement is different from the Heyns rearrangement in that the α-amino ketones were obtained without the shift of the carbonyl group. The key to success is using chiral primary amine as a catalyst by mimicking glucosamine-6-phosphate synthase in catalyzing the efficient Heyns rearrangement in organisms.
- Chen, Yue,Cui, Xin,Li, Guang-Xun,Nie, Xiao-Kang,Tang, Zhuo,Zhang, Shi-Qi
-
supporting information
p. 2069 - 2074
(2022/03/31)
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- Iridium Complexes as Efficient Catalysts for Construction of α-Substituted Ketones via Hydrogen Borrowing of Alcohols in Water
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Ketones are of great importance in synthesis, biology, and pharmaceuticals. This paper reports an iridium complexes-catalyzed cross-coupling of alcohols via hydrogen borrowing, affording a series of α-alkylated ketones in high yield (86 %–95 %) and chemoselectivities (>99 : 1). This methodology has the advantages of low catalyst loading (0.1 mol%) and environmentally benign water as the solvent. Studies have shown the amount of base has a great impact on chemoselectivities. Meanwhile, deuteration experiments show water plays an important role in accelerating the reduction of the unsaturated ketones intermediates. Remarkably, a gram-scale experiment demonstrates this methodology of iridium-catalyzed cross-coupling of alcohols has potential application in the practical synthesis of α-alkylated ketones.
- Luo, Nianhua,Zhong, Yuhong,Wen, Huiling,Shui, Hongling,Luo, Renshi
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p. 1355 - 1364
(2021/03/03)
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- Copper-catalyzed method for preparing aldehyde or ketone compound by oxidizing alcohol with oxygen as oxidizing agent and application
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The invention discloses a copper-catalyzed method for preparing an aldehyde or ketone compound by oxidizing alcohol with oxygen as an oxidizing agent. Reaction is performed in an organic solvent for 4-48 hours at room temperature by using copper salt and nitroxide free radicals as catalysts and oxygen or air as an oxidizing agent to efficiently oxidize an alcohol compound into the corresponding aldehyde or ketone compound. The method is simple to operate, free of chlorides corrosive to equipment, available in raw materials and reagents, mild in reaction conditions, wide in substrate universality, good in functional group compatibility, convenient in separation and purification, environmentally friendly in the whole process and free of pollution, and is a method suitable for industrial production.
- -
-
Paragraph 0028-0030; 0154-0156
(2020/08/18)
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- Metal-Free Photoinduced Transformation of Aryl Halides and Diketones into Aryl Ketones
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The acylation of aryl halides to prepare aryl ketones without metal catalyst represents an important yet challenging topic towards more sustainable ketone synthesis. Herein, we describe a simple and efficient metal-free protocol for the acylation of aryl halides with diketone under the irradiation of light utilizing N-methylpiperidine as base under an air atmosphere. This reaction can tolerate a wide range of functional groups and the corresponding ketones can be obtained in modest to good yields.
- Yao, Qiuli,Liu, Wenbo,Liu, Peng,Ren, Linjing,Fang, Xuehong,Li, Chao-Jun
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supporting information
p. 2721 - 2724
(2019/01/14)
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- Isomerization of Allylic Alcohols to Ketones Catalyzed by Well-Defined Iron PNP Pincer Catalysts
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[Fe(PNP)(CO)HCl] (PNP=di-(2-diisopropylphosphanyl-ethyl)amine), activated in situ with KOtBu, is a highly active catalyst for the isomerization of allylic alcohols to ketones without an external hydrogen supply. High reaction rates were obtained at 80 °C, but the catalyst is also sufficiently active at room temperature with most substrates. The reaction follows a self-hydrogen-borrowing mechanism, as verified by DFT calculations. An alternative isomerization through alkene insertion and β-hydride elimination could be excluded on the basis of a much higher barrier. In alcoholic solvents, the ketone product is further reduced to the saturated alcohol.
- Xia, Tian,Wei, Zhihong,Spiegelberg, Brian,Jiao, Haijun,Hinze, Sandra,de Vries, Johannes G.
-
supporting information
p. 4043 - 4049
(2018/01/27)
-
- Synthesis method for 3-methoxypropiophenone
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The invention discloses a synthesis method for 3-methoxypropiophenone. The synthesis method comprises the steps of enabling magnesium and m-bromoanisole to produce a Grignard reagent in a tetrahydrofuran (THF) solution under the catalytic action of aluminum chloride, and then, subjecting the Grignard reagent to a reaction with propionitrile, thereby producing the 3-methoxypropiophenone. According to the synthesis method, the operation is simple, the process is advanced, the solvent can be recycled, and thus, the industrial production is facilitated. According to the 3-methoxypropiophenone prepared by the synthesis method, the yield reaches 88.6%, and the liquid-phase purity reaches up to 99.44% or more.
- -
-
Paragraph 0018-0033
(2017/07/14)
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- KOtBu-Mediated Domino Isomerization and Functionalization of Aromatic Allylic Alcohols
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Transition-metal- as well as ligand-free base-mediated domino isomerization and alkylation of allylic alcohols is presented. This protocol features the conversion of simple allylic alcohols into the corresponding ketones through isomerization in the presence of a simple base. Significantly, these in situ generated ketones subsequently undergo alkylation with styrenes as electrophiles, in a domino one-pot fashion, as an atom- and step-economical chemical process.
- Suchand, Basuli,Satyanarayana, Gedu
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p. 3886 - 3895
(2017/07/22)
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- Targeting Cancer with PCPA-Drug Conjugates: LSD1 Inhibition-Triggered Release of 4-Hydroxytamoxifen
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Targeting cancer with small molecule prodrugs should help overcome problems associated with conventional cancer-targeting methods. Herein, we focused on lysine-specific demethylase 1 (LSD1) to trigger the controlled release of anticancer drugs in cancer cells, where LSD1 is highly expressed. Conjugates of the LSD1 inhibitor trans-2-phenylcyclopropylamine (PCPA) were used as novel prodrugs to selectively release anticancer drugs by LSD1 inhibition. As PCPA-drug conjugate (PDC) prototypes, we designed PCPA-tamoxifen conjugates 1 a and 1 b, which released 4-hydroxytamoxifen in the presence of LSD1 in vitro. Furthermore, 1 a and 1 b inhibited the growth of breast cancer cells by the simultaneous inhibition of LSD1 and the estrogen receptor without exhibiting cytotoxicity toward normal cells. These results demonstrate that PDCs provide a useful prodrug method that may facilitate the selective release of drugs in cancer cells.
- Ota, Yosuke,Itoh, Yukihiro,Kaise, Asako,Ohta, Kiminori,Endo, Yasuyuki,Masuda, Mitsuharu,Sowa, Yoshihiro,Sakai, Toshiyuki,Suzuki, Takayoshi
-
supporting information
p. 16115 - 16118
(2016/12/26)
-
- TETRAZOLINONE COMPOUND AND USE THEREOF
-
A tetrazolinone compound represented by formula (1): wherein R1 and R2 each represents a hydrogen atom, a halogen atom, or a C1-C3 alkyl group; R3 represents a C1-C3 alkyl group optionally having one or more halogen atoms; R4, R5, and R6 each represents a hydrogen atom or a halogen atom; R7 represents a C1-C3 alkyl group; Q represents a divalent group selected from Group P4; and A represents a C7-C18 aralkyloxy group optionally having one or more atoms or groups selected from Group P3, has excellent control activity against pests.
- -
-
Paragraph 0485
(2016/09/12)
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- DMF as carbon source: Rh-catalyzed α-methylation of ketones
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An unprecedented Rh-catalyzed direct methylation of ketones with N,N-dimethylformamide (DMF) is disclosed. The reaction shows a broad substrate scope, tolerating both aryl and alkyl ketones with various substituents. Mechanistic studies suggest that DMF delivers a methylene fragment followed by a hydride in the methylation process.
- Li, Yang,Xue, Dong,Lu, Wei,Wang, Chao,Liu, Zhao-Tie,Xiao, Jianliang
-
supporting information
p. 66 - 69
(2014/01/23)
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- Rhodium-catalyzed ketone methylation using methanol under mild conditions: Formation of α-branched products
-
The rhodium-catalyzed methylation of ketones has been accomplished using methanol as the methylating agent and the hydrogen-borrowing method. The sequence is notable for the relatively low temperatures that are required and for the ability of the reaction system to form α-branched products with ease. Doubly alkylated ketones can be prepared from methyl ketones and two different alcohols by using a sequential one-pot iridium- and rhodium-catalyzed process. Uniquely effective for making branched alkyl products from ketones (see scheme): The scope of the presented reaction includes aromatic and aliphatic ketones and consecutive one-pot double alkylation reactions to provide a convenient route to branched ketones from simple methyl ketones. A brief study into the mechanism of the reaction has given evidence for an aldol-based reaction pathway.
- Chan, Louis K. M.,Poole, Darren L.,Shen, Di,Healy, Mark P.,Donohoe, Timothy J.
-
supporting information
p. 761 - 765
(2014/01/23)
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- A versatile synthesis of O-desmethylangolensin analogues from methoxy-substituted benzoic acids
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The synthesis of O-desmethylangolensin (O-DMA) analogues from methoxy-substituted benzoic acids was described. Treatment of methoxy-substituted benzoic acids with 2 equiv of ethyllithium afforded methoxypropiophenones, which were subsequently transformed to ethyl 2-(methoxyphenyl)propionates via 1,2-rearrangement of the methoxyphenyl group using Pb(OAc)4/HClO4 in triethyl orthoformate. After hydrolysis with KOH, the 2-(methoxyphenyl)propionic acids were reacted with di- 2-pyridyl carbonate to afford 2-pyridyl 2-(methoxyphenyl)propionates, which were acylated with methoxy-substituted phenylmagnesium bromides to give methoxy-α-methyldesoxybenzoins. The methoxy groups of these compounds were selectively or fully demethylated using boron tribromide to give diverse O-DMA analogues in high yields.
- Hong, Hyo Jeong,Lee, Jae In
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p. 569 - 574
(2015/02/05)
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- Phosphodiesterase inhibitors. Part 5: Hybrid PDE3/4 inhibitors as dual bronchorelaxant/anti-inflammatory agents for inhaled administration
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(-)-6-(7-Methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl) -5-methyl-4,5-dihydropyridazin-3(2H)-one (KCA-1490) exhibits moderate dual PDE3/4-inhibitory activity and promises as a combined bronchodilatory/anti- inflammatory agent. N-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses PDE3 inhibition. Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the N-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent PDE3 inhibition. Both dihydropyridazinone rings, in the core and extension, can be replaced by achiral 4,4-dimethylpyrazolone subunits and the core pyrazolopyridine by isosteric bicyclic heteroaromatics. In combination, these modifications afford potent dual PDE3/4 inhibitors that suppress histamine-induced bronchoconstriction in vivo and exhibit promising anti-inflammatory activity via intratracheal administration.
- Ochiai, Koji,Takita, Satoshi,Kojima, Akihiko,Eiraku, Tomohiko,Iwase, Kazuhiko,Kishi, Tetsuya,Ohinata, Akira,Yageta, Yuichi,Yasue, Tokutaro,Adams, David R.,Kohno, Yasushi
-
supporting information
p. 375 - 381
(2013/02/23)
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- Efficient and scalable synthesis of ketones via nucleophilic Grignard addition to nitriles using continuous flow chemistry
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In the present Letter we report the development of efficient continuous flow chemistry conditions for the scalable preparation of ketones. This transformation is achieved via nucleophilic addition of Grignard reagents to the corresponding nitriles and imine hydrolysis by means of in-series plug flow reactors.
- Mateos, Carlos,Rincón, Juan A.,Villanueva, José
-
supporting information
p. 2226 - 2230
(2013/05/08)
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- Catalytic isomerization of allylic alcohols promoted by complexes [RuCl2(η6-arene)(PTA-Me)] under homogeneous conditions and supported on Montmorillonite K-10
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The mononuclear arene-ruthenium(II) derivatives [RuCl2(η 6-arene)(PTA-Me)] (arene = C6H6 (3a), p-cymene (3b), 1,3,5-C6H3Me3 (3c), C6Me 6 (3d)), containing the ionic phosphine ligand 1-methyl-3,5-diaza-1- azonia-7-phosphaadamantane chloride (PTA-Me), have been synthesized and fully characterized. These complexes were evaluated as potential catalysts for the redox isomerization of allylic alcohols. Among them, best results in terms of activity were obtained with complex [RuCl2(η6-C 6H6)(PTA-Me)] (3a) which, in combination with K 2CO3 (2.5 equiv. per Ru), was able to selectively isomerize a number of allylic alcohols RCH(OH)CHCH2 (R = H, aryl, alkyl or heteroaryl group) into the corresponding carbonyl compounds RC(O)CH2CH3 in refluxing THF (TOF values up to 800 h -1). Complex [RuCl2(η6-C6H 6)(PTA-Me)] (3a) was adsorbed onto the Montmorillonite K-10 clay, and the resulting solid proved also active in the isomerization of the model substrate 1-octen-3-ol. In addition, it could be easily separated from the reaction media by simple filtration and reused several times (up to 11 consecutive runs) with retention of its efficiency.
- Menéndez-Rodríguez, Lucía,Crochet, Pascale,Cadierno, Victorio
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p. 390 - 399
(2013/02/21)
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- A NOVEL PROCESS FOR THE PREPARATION OF TAPENTADOL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Disclosed herein is a novel, commercially viable and industrially advantageous process for the preparation of 3-[(1R,2R))-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol (Tapentadol), or a pharmaceutically acceptable salt thereof, in high yield and purity. Also described are novel intermediates useful for preparing tapentadol or a pharmaceutically acceptable salt thereof.
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Page/Page column 14-15
(2012/11/13)
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- NOVEL COMPOUNDS
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The present invention relates to novel NADPH oxidase II inhibitors and their use in the treatment of diseases mediated by the NADPH oxidase II enzyme.
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- A facile synthesis of α-fluoro ketones catalyzed by [Cp*IrCl2]2
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Allylic alcohols are isomerized into enolates (enols) by [Cp*IrCl2]2. The enolates react with Selectfluor present in the reaction media. This method produces α-fluoro ketones as single constitutional isomers in high yields. Georg Thieme Verlag Stuttgart. New York.
- Ahlsten, Nanna,Bartoszewicz, Agnieszka,Agrawal, Santosh,Martin-Matute, Belen
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p. 2600 - 2608
(2011/10/02)
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- N, N′-dioxide-Cu(OTf)2 complex catalyzed highly enantioselective amination reaction of N-acetyl enamide
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The N,N′-dioxide-Cu(OTf)2 complexes were applied in the asymmetric amination reaction of N-acetyl enamides with dialkyl azodicarboxylate, giving the corresponding products in good yields with high enantioselectivities (up to 91% ee). Precursors of vicinal diamine were readily obtained with excellent diastereoselectivities (>95:5) by NaBH4 reduction.
- Chang, Lu,Kuang, Yulong,Qin, Bo,Zhou, Xin,Liu, Xiaohua,Lin, Lili,Feng, Xiaoming
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supporting information; scheme or table
p. 2214 - 2217
(2010/08/06)
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- PYRIDAZINONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
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It is to provide a novel pyridazinone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1 represents H or C1-6 alkyl, each of R2 and R3 represents H, X, C1-6 alkoxy, Z represents O or S, and A represents AA or BB, wherein AA represents: and BB represents: wherein R4 represents H or C1-6 alkyl, and each of R5 and R6 represents C1-6 alkyl.
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Page/Page column 161
(2010/04/25)
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- PYRAZOLONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
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It is to provide a novel pyrazolone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1,R2: C1-6 alkyl; R3,R4: H, X, C1-6 alkoxy; Z:O, S; A:AA, BB, wherein AA represents wherein BB represents wherein R5: H, C1-6 alkyl ; R6,R7: C1-6 alkyl.
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Page/Page column 111
(2010/04/25)
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- Ruthenium-catalyzed redox isomerization/transfer hydrogenation in organic and aqueous media: A one-pot tandem process for the reduction of allylic alcohols
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The hexamethylbenzene-ruthenium(ii) dimer [{RuCl(μ-Cl) (η6-C6Me6)}2] 1 and the mononuclear bis(allyl)-ruthenium(iv) complex [RuCl2(η 3:η2:η3-C12H 18)]2, associated with base and a hydrogen donor, were found to be active catalysts for the selective reduction of the CC bond of allylic alcohols both in organic and aqueous media. The process, which proceeds in a one-pot manner, involves a sequence of two independent reactions: (i) the initial redox-isomerization of the allylic alcohol, and (ii) subsequent transfer hydrogenation of the resulting carbonyl compound. The highly efficient transformation reported herein represents, not only an illustrative example of auto-tandem catalysis, but also an appealing alternative to the classical transition-metal catalyzed CC hydrogenations of allylic alcohols. The process has been successfully applied to aromatic as well as aliphatic substrates affording the corresponding saturated alcohols in 45-100% yields after 1.5-24 h. The best performances were reached using (i) 1-5 mol% of 1 or 2, 2-10 mol% of Cs2CO3, and propan-2-ol or (ii) 1-5 mol% of 1 or 2, 10-15 equivalents of NaO2CH, and water. The catalytic efficiency is strongly related to the structure of the allylic alcohol employed. Thus, in propan-2-ol, the reaction rate essentially depends on the steric requirement around the CC bond, therefore decreasing with the increasing number of substituents. On other hand, in water the transformation is favoured for primary allylic alcohols vs. secondary ones.
- Cadierno, Victorio,Crochet, Pascale,Francos, Javier,Garcia-Garrido, Sergio E.,Gimeno, Jose,Nebra, Noel
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scheme or table
p. 1992 - 2000
(2010/06/19)
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- CHEMICAL COMPOUNDS
-
The present invention discloses novel compounds with a variety of therapeutic uses. More particularly, the invention discloses novel symmetrical triphenyl compounds that are particularly useful for selective estrogen receptor modulation.
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-
- CHEMICAL COMPOUNDS
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The present invention discloses to novel compounds with a variety of therapeutic uses. More particularly, the invention discloses novel symmetrical triphenyl compounds that are particularly useful for selective estrogen receptor modulation.
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Page/Page column 29; 30
(2008/06/13)
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- PYRIDAZINONE COMPOUNDS AS CALCILYTICS
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Various calcilytic compounds and pharmaceutical compositions containing these compounds are disclosed. Calcilytic compounds are compounds capable of inhibiting calcium receptor activity. Methods for preparing calcilytic compounds, oral bioavailability of calcilytic compounds, and their use as calcium receptor antagonists are also disclosed.
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Page/Page column 35-36
(2010/11/27)
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- Method of treating filariae
-
The present invention relates to a novel method for treating a mammal suffering from filariae.
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- Photochemistry of substituted propiophenones: An interesting α-and aryl substituents effect on their photobehaviour
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Photochemistry of different α-substituted and phenyl-substituted propiophenones in methanol is investigated with a view to delineate the substituent effect with a special reference tu their rearrangement to α-arylpropanoic acids, an important class of nonsteroidal antiinflammatory agents. The results thus obtained bringsforth an important element of their reactivityprofile i.e. the α-chloro-substituent in combination with nuclear alkyl substituents (para>meta) favours 1,2-arylmigration leading to the synthetically useful reaction for α-arylpro panoic acids.
- Sonawane, Harikisan R.,Bellur, Nanjundiah S.,Nazeruddin
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p. 11281 - 11294
(2007/10/02)
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- Synthesis and activity of 2-methyl-3-aminopropiophenones as centrally acting muscle relaxants
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Some novel 2-methyl-3-aminopropiophenones were synthesized and their centrally acting muscle relaxant activities were,evaluated for an inhibitory effect on the flexor reflex in rats. The structure-activity relationships are discussed. In this series 2-methyl-3-pyrrolidino-1-(4-trifluoromethylphenyl)-propan-1-one (28) showed significant centrally acting muscle relaxant activity. In addition, the activities of each enantiomer (28-(S) and (R)) were studied along with their acute toxicities. Compound 28-(R) was found to exhibit more potent activity and weaker acute toxicity than 28-(S). Accordingly, compound 28-(R) (NK433) is under development as a novel centrally acting muscle relaxant.
- Shiozawa,Narita,Izumi,Kurashige,Sakitama,Ishikawa
-
-
- Tetraorganogallate complexes in organic chemistry: A novel, efficient and versatile preparation of ketones from acyl chlorides
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Tetraorganogallium ate complexes, prepared in situ by addition of an organolithium reagent to a triorganogallium, reacted smoothly with acyl chlorides to yield ketones in high yields and mixed ate complexes display high chemoselectivity in the transfer of one of their ligands.
- Han, Ying,Fang, Lei,Tao, Wen-Tian,Huang, Yao-Zeng
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p. 1287 - 1290
(2007/10/02)
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- Heterocyclic carboxylic acids
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Novel N-substituted azaheterocyclic carboxylic acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent, the compounds thus having the general formula I STR1 wherein Y is STR2 wherein R1 and R2 independently are C3-8 cycloalkyl phenyl or thienyl all of which may be optionally substituted with halogen, trifluoromethyl, C1-16 alkyl or C1-6 alkoxy; s is 1, 2 or 3; x is --CH2 --, --O-- or STR3 -wherein R3 is hydrogen or C1-6 -alkyl; r is 2, 3 or 4; R4 and R5 each represents hydrogen or may together represent a bond and R6 is OH or C1-8 -alkoxy; and pharmaceutically acceptable acid addition salts are potent inhibitors of GABA uptake from the synaptic cleft.
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- Heterocyclic thiazole derivatives and pharmaceutical compositions comprising said derivatives
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The invention concerns a thiazole of the formula I, STR1 wherein Q1 is an optionally substituted 6-membered monocyclic or 10-membered bicyclic heterocyclic moiety containing one or two nitrogen atoms; X is oxy, thio, sulphinyl, sulphonyl or imino; Ar is phenylene which may optionally bear one or two substituents, or Ar is an optionally substituted 6-membered heterocyclene moiety continuing up to three nitrogen atoms; R1 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl or substituted (1-4C)alkyl; R2 is hydrogen, (1-6C)alkyl, (3-6C)alkenyl, (3-6C)alkynyl or substituted (1-4C)alkyl or R2 is optionally substituted benzoyl; and Q2 is optionally substituted thiazolyl; or a pharmaceutically-acceptable salt thereof. The invention also concerns processes for the manufacture of a thiazole of the formula I and pharmaceutical compositions containing said thiazole.
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-
- (Methoxyalkyl)thiazoles: A new series of potent, selective, and orally active 5-lipoxygenase inhibitors displaying high enantioselectivity
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(Methoxyalkyl)thiazoles are novel 5-lipoxygenase (5-LPO) inhibitors that are neither redox agents nor iron chelators. Consideration of a hypothetical model of the enzyme active site led to this series which is exemplified by 1-[3(naphth-2-ylmethoxy)phenyl]-1-(thiazol-2-yl)propyl methyl ether (2d, ICI211965). 2d inhibits cell-free guinea pig 5-LPO activity, LTC4 synthesis in plasma free mouse macrophages, and LTB4 synthesis in rat and human blood (IC50s 0.1 μM, 8nM, 0.5 μM, and 0.4 μM, respectively) but does not inhibit the synthesis of cyclooxygenase products at concentrations up to 50 μM in macrophages and 100 μM in blood. 2d is orally active in rat (ex vivo ED50 10 mg/kg in blood taken in 1h after dosing). SAR studies show that high in vitro potency requires methoxy, thiazolyl, and naphthyl groups and depends critically on the substitution pattern. (Methoxyalkyl)thiazoles are chiral. Resolution of 1-methoxy-6-(naphth-2-ylmethoxy)-1-(thiazol-2-yl)indan (2j, ICl216800) shows that (+)-2j is 50-150-fold more potent than (-)-2j in in vitro assays. Thus, (methoxyalkyl)thiazoles are a new series of orally active, selective 5-LPO inhibitors and represent the first class of inhibitors in which inhibition is mediated by specific, enantioselective interactions with the enzyme.
- Bird,Bruneau,Crawley,Edwards,Foster,Girodeau,Kingston,McMillan
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p. 2176 - 2186
(2007/10/02)
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- Quinoline dioic acids and amides
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Compounds having the formula are antagonists of leukotrienes and inhibitors of their biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents.
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-
- Heterocyclic derivatives
-
The invention concerns a thiazole of the formula I, wherein Q1 is an optionally substituted 6-membered monocyclic or 10-membered bicyclic heterocyclic moiety containing one or two nitrogen atoms;, X is oxy, thio, sulphinyl, sulphonyl or imino;, Ar is phenylene which may optionally bear one or two substituents, or Ar is an optionally substituted 6-membered heterocyclene moiety contining up to three nitrogen atoms;, R1 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl or substituted (1-4C)alkyl;, R2 is hydrogen, (1-6C)alkyl, (3-6C)alkenyl, (3-6C)alkynyl or substituted (1-4C)alkyl or R2 is optionally substituted benzoyl; and, Q2 is optionally substituted thiazolyl;, or a pharmaceutically-acceptable salt thereof. The invention also concerns processes for the manufacture of a thiazole of the formula I and pharmaceutical compositions containing said thiazole.
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-
- Reaction of some N-acyl-1-alkylamines with polyphosphoric ester PPE: nuclear magnetic resonance and stereochemistry of reaction products
-
Phenylindanes were obtained from the reaction of N-acyl-1-arylalkylamines with polyphosphoric ester (PPE). cis-1-Methyl-3-(3,4-dimethoxyphenyl)-5,6-dimethoxyindane was synthesized to determine which stereoisomer was produced by N-formyl and N-acetyl-1-(3,4-dimethoxyphenyl)ethylamine with PPE.Nuclear magnetic resonance specta (1H and 13C) of several mono-, 1,3-di-, and 1,2,3-tri-substituted indanes were fully analyzed to provide information on steric interactions and conformation of the cyclopentene ring.Possible cyclodimerization pathways are proposed.
- Alesso, Elba N.,Tombari, Dora G.,Iglesias, Graciela Y. Moltrasio,Aguirre, Jose M.
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p. 2568 - 2574
(2007/10/02)
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