- Hemilabile Benzyl Ether Enables Γ-C(sp3)-H Carbonylation and Olefination of Alcohols
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Pd-catalyzed C(sp3)-H activation of alcohol typically shows β-selectivity due to the required distance between the chelating atom in the attached directing group and the targeted C-H bonds. Herein we report the design of a hemilabile directing group which exploits the chelation of a readily removable benzyl ether moiety to direct Γ- or δ-C-H carbonylation and olefination of alcohols. The utility of this approach is also demonstrated in the late-stage C-H functionalization of β-estradiol to rapidly prepare desired analogues that required multi-step syntheses with classical methods.
- Tanaka, Keita,Ewing, William R.,Yu, Jin-Quan
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p. 15494 - 15497
(2019/10/16)
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- Hemilabile Benzyl Ether Enables γ-C(sp3)-H Carbonylation and Olefination of Alcohols
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Pd-catalyzed C(sp3)-H activation of alcohol typically shows β-selectivity due to the required distance between the chelating atom in the attached directing group and the targeted C-H bonds. Herein we report the design of a hemilabile directing group which exploits the chelation of a readily removable benzyl ether moiety to direct γ- or δ-C-H carbonylation and olefination of alcohols. The utility of this approach is also demonstrated in the late-stage C-H functionalization of β-estradiol to rapidly prepare desired analogues that required multi-step syntheses with classical methods.
- Tanaka, Keita,Ewing, William R.,Yu, Jin-Quan
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- Inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies
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1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.
- Deng, Lisheng,Diao, Jiasheng,Chen, Pinhong,Pujari, Venugopal,Yao, Yuan,Cheng, Gang,Crick, Dean C.,Prasad, B. V. Venkataram,Song, Yongcheng
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p. 4721 - 4734
(2011/09/19)
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- Synthesis and structure-activity relationships of aza- and diazabiphenyl analogues of the antitubercular drug (6 S)-2-nitro-6-{[4-(trifluoromethoxy) benzyl]oxy}-6,7-dihydro-5 H-imidazo[2,1-b][1,3]oxazine (PA-824)
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New heterocyclic analogues of the potent biphenyl class derived from antitubercular drug PA-824 were prepared, aiming to improve aqueous solubility but maintain high metabolic stability and efficacy. The strategy involved replacement of one or both phenyl
- Kmentova, Iveta,Sutherland, Hamish S.,Palmer, Brian D.,Blaser, Adrian,Franzblau, Scott G.,Wan, Baojie,Wang, Yuehong,Ma, Zhenkun,Denny, William A.,Thompson, Andrew M.
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experimental part
p. 8421 - 8439
(2011/02/21)
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- BICYCLIC NITROIMIDAZOLES COVALENTLY LINKED TO SUBSTITUTED PHENYL OXAZOLIDINONES
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The current invention provides a series of bicyclic nitroimidazole- substituted phenyl oxazolidinones in which a bicyclic nitroimidazole pharmacophore is covalently bonded to a phenyl oxazolidinone, their pharmaceutical compositions, and the method of use of the compositions for prevention and treatment of bacterial infections. The bicyclic nitroimidazole-substituted phenyl oxazolidinones possess surprising antibacterial activity against wild- type and resistant strains of pathogens, and are therefore useful for the prevention, control and treatment of a number of human and veterinary bacterial infections caused by these pathogens, such as Mycobacterium tuberculosis.
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- ION CHANNEL MODULATORS
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The present teachings provide carboxylic amide compounds that can modulate the activity of ion channels in a mammal. The present teachings also provide processes for producing said compounds and their pharmaceutically acceptable salts, hydrates and esters, and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds including their pharmaceutically acceptable salts, hydrates and esters. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.
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Page/Page column 132; 133
(2008/12/06)
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- ION CHANNEL MODULATORS
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The present teachings provide compounds of Formula (I): and pharmaceutically acceptable salts, hydrates, and esters thereof, wherein Ar, R1, R2, R3, p, and X are defined herein. The present teachings also provide processes for producing said compounds and their pharmaceutically acceptable salts, hydrates and esters, and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds including their pharmaceutically acceptable salts, hydrates and esters. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.
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Page/Page column 86; 93
(2008/12/06)
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- ION CHANNEL MODULATORS
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The present teachings provide compounds of Formula (I) and pharmaceutically acceptable salts, hydrates, and esters thereof, wherein Ar, R1, R1', R2, R3, R4 R4', and p are defined herein. The present teachings also provide processes for producing said compounds and their pharmaceutically acceptable salts, hydrates and esters, and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds including their pharmaceutically acceptable salts, hydrates and esters. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.
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Page/Page column 55; 63
(2008/12/06)
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- CARBOXAMIDE DERIVATIVES AS ION CHANNEL MODULATORS
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The present teachings provide compounds of Formula (I) wherein Ar, R1, R2, R3, X, p and n are defined herein. The present teachings also provide processes for producing said compounds and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.
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Page/Page column 83; 88; 95
(2008/12/06)
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- TRISUBSTITUTED AMINE COMPOUND
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The present invention relates to a compound of the general formula (1): wherein, Y is a methylene group, and the like; A is an optionally substituted heterocyclic group, and the like; B is an optionally substituted heterocyclic group, and the like; R1 is an optionally substituted alkyl group, wherein the alkyl group further may optionally be substituted by an optionally substituted homocyclic group, and the like; and R2 is an optionally substituted amino group, and the like; or a pharmaceutically acceptable derivative thereof, which has an inhibitory activity against cholesteryl ester transfer protein (CETP), thereby being useful for prophylaxis and/or treatment of arteriosclerotic diseases, hyperlipemia or dyslipidemia, and the like.
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Page/Page column 115-116
(2008/06/13)
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- Novel aminopyridine compounds having Syk inhibitory activity
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The present invention relates to an aminopyridine compound represented by the following general formula (I) or a salt thereof and an Syk inhibitor containing the compound or a salt thereof as an active ingredient. Here, X1, X2, Xsup
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Page/Page column 52
(2010/11/23)
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- 1, 6 -DIHYDRO- 1,3, 5, 6-TETRAAZA-AS-INDACENE BASED TRICYCLIC COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS COMPRISING SAME AS INHIBITORS OF IKK ENZYME ACTIVITY
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The present invention provides for tricyclic compounds having the formula (I) wherein R1, R2, R5, R6, R7, and R8 are as described herein. The present invention further provides pharmaceutical compositions comprising such compounds, as well as the use of such compounds for treating inflammatory and immune diseases.
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Page/Page column 156; 156-157
(2010/11/24)
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- NEW COMPOUNDS
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The present invention relates to new compounds of formula I, wherein P Q X1 X2 X3 X4 X5 R R1 R2 R3 R4R5 G M1 M2 M3 m and n are defined as in formula I, a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said compounds and to the use of said compounds in therapy.
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