- Synthesis method of elagolix intermediate
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The invention relates to a synthesis method of an elagolix intermediate. Specifically, the invention provides a synthesis method of an elagolix intermediate compound X and an elagolix intermediate compound I. According to the method, 2-fluoro-3-methoxy-phenylacetic acid is used as a raw material, and the steps of cyclization, hydrolysis, amino protection, condensation, Mitsunobu reaction and the like are carried out in sequence, so that the elagolix intermediate compound X and the elagolix intermediate compound I are obtained. The method has the advantages of cheap and easily available reagents, high conversion rate, simple operation and low process cost, and is suitable for industrialization.
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Paragraph 0113; 0119-0121
(2020/02/17)
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- BORON-CONTAINING SMALL MOLECULES
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This invention provides novel compounds of the following formula and pharmaceutical compositions containing such compounds.
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Paragraph 0234
(2015/02/19)
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- Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases
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Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferati
- Dakin, Les A.,Block, Michael H.,Chen, Huawei,Code, Erin,Dowling, James E.,Feng, Xiaomei,Ferguson, Andrew D.,Green, Isabelle,Hird, Alexander W.,Howard, Tina,Keeton, Erika K.,Lamb, Michelle L.,Lyne, Paul D.,Pollard, Hannah,Read, Jon,Wu, Allan J.,Zhang, Tao,Zheng, Xiaolan
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scheme or table
p. 4599 - 4604
(2012/08/07)
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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 141
(2010/04/25)
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- 1-AMINO-2-OXY-SUBSTITUTED TETRAHYDRONAPHTALENE DERIVATIVES, METHODS FOR THE PRODUCTION THEREOF, AND THEIR USE AS ANTIPHLOGISTICS
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The invention relates to polysubstituted tetrahydronaphtalene derivatives of formula (I), to methods for the production thereof, and to their use as antiphlogistics. The substituents are defined in Claim 1.
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Page/Page column 67
(2010/02/11)
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- HALO SUBSTITUTED BENZO`B! THIOPHENES WITH PI3K INHIBITORY ACTIVITY AS THERAPEUTIC AGENTS
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The present invention provides benzo[b]thiophenes of Formula (I), wherein R3, R4, R5, R6, R7, Y, and L have any of the values defined therefor in the specification, and pharmaceutically acceptable sal
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Page/Page column 54
(2010/02/11)
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- 3-ARYLOXY/ THIO-2, 3-SUBSTITUTED PROPANAMINES AND THEIR USE IN INHIBITING SEROTONIN AND NOREPINEPHRINE REUPTAKE
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There is provided a compound of formula (I) wherein A is selected from -O- and -S-; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C1-C4 alkyl and C1-C4 alkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C1-C4 alkyl, and C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, -CF3, -CN and -CONH2; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, nitro, acetyl, -CF3, -SCF3 and cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C1-C4 alkyl; Z is selected from OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; and pharmaceutically acceptable salts thereofwith the proviso that when Y is optionally substituted phenyl or optionally substituted 1,3-benzodioxolyl and Z is OR3 and X is optionally substituted phenyl then A is -S-.
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Page 66 - 67
(2010/02/07)
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- PROPANAMINE DERIVATIVES AS SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS
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There is provided a heretoaryloxy/thio 3-substituted propanamine compound of formula (I) wherein A is selected from -O- and -S-; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C1-C4 alkyl and C1-C4 alkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C1-C4 alkyl, and C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, -CF3, -CN and -CONH2; Y is selected from dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, and thienopyridyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, nitro, acetyl, -CF3, -SCF3 and cyano; Z is selected from H, OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; and pharmaceutically acceptable salts thereof.
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- Unexpected Regioselectivity in the Lithiation of Fluoroanisoles
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The regioselectivity of lithiation of a series of fluoroanisoles and fluoroveratroles has been studied by determining the ratio of isomeric aldehydes produced by dimethylformamide quenching.The position of lithiation is influenced by such factors as temperature and time of the reaction.Contrary to published reports, fluorine competes significantly with the methoxy group as an ortho director in lithiation reactions.Lithiation of dimethyl-tert-butylsilyl ethers of fluorophenols proceeds exclusively ortho to fluorine.
- Furlano, David C.,Calderon, Silvia N.,Chen, George,Kirk, Kenneth L.
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p. 3145 - 3147
(2007/10/02)
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- Synthesis and Adrenergic Activity of Ring-Fluorinated Phenylephrines
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2-Fluoro-, 4-fluoro-, and 6-fluorophenylephrine (6-FPE) were synthesized from the corresponding fluorinated 3-hydroxybenzaldehydes.New routes to 2-fluoro- and 6-fluoro-3-hydroxybenzaldehydes were developed based on regioselective lithiation of 2- and 4-fluorobenzene ortho to fluorine.As with norepinephrine and isoproterenol analogues, the adrenergic properties of phenylephrine were markedly altered by ring fluorination.The order of potency of the fluoro analogues as α1-adrenergic agonists in the stimulation of contraction of aorticstrips and of phosphatidylinositol turnover and potentiation of cyclic AMP accumulation in guinea pig synaptoneurosomes was 6-FPE > PE > 4-FPE > 2-FPE.The same pattern was observed for the displacement of radioligands specific for α1- and α2-adrenergic receptors on brain membranes.The order of potency for the displacement of 3H>dihydroalprenolol, a β-specific adrenergic ligand from brain membranes, was 2-FPE > 4-FPE = PE >> 6-FPE. 6-FPE was much more selective for α-adrenergic receptors compared to β-receptors than was phenylephrine.A rationale for the observed fluorine-induced alterations in potency and selectivity of the FPEs for α- and β-adrenergic systems is presented based on fluorine-induced conformations due to electrostatic repulsion of fluorine and the benzyl hydroxyl group.
- Kirk, Kenneth L.,Olubajo, Olarangbe,Buchhold, Konstantin,Lewandowski, Gail A.,Gusovsky, Fabian,et al.
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p. 1982 - 1988
(2007/10/02)
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