- Effective synthesis of novel dihydrobenzisoxazoles bearing the 2-aminothiazole moiety and evaluation of the antiproliferative activity of their acylated derivatives
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An effective method for the synthesis of 8-aryl-4,5-dihydrothiazolo[4′,5′:3,4]benzo[1,2-c]isoxazol-2-amines was developed. This method includes the α-keto bromination of 3-aryl-6,7-dihydrobenzo[c]isoxazol-4(5H)-ones followed by the condensation of the obt
- Khlebnicova, Tatyana S.,Lakhvich, Fedor A.,Matous, Anton E.,Piven, Yuri A.,Scherbakov, Alexander M.,Shchegolev, Yuri Yu.,Sorokin, Danila V.,Yastrebova, Margarita A.,Zinovich, Veronica G.
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p. 10432 - 10443
(2021/12/17)
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- Triazole derivative having HSP90 (Heat Shock Protein) inhibiting activity, as well as preparation method and application of triazole derivative
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The invention discloses a triazole derivative having an HSP90 (Heat Shock Protein) inhibiting activity, as well as a preparation method and an application of the triazole derivative. Specifically, the invention relates to the triazole derivative having a structure as shown in a formula (I), a stereisomer of the triazole derivative and a pharmaceutically acceptable salt, wherein the definition of each substituent group in the formula (I) and the definition in a description are the same. The compound with a novel structure has the HSP90 inhibiting activity, can be used to cure cancers, neurodegenerative disorders, inflammation diseases, autoimmune diseases, ischemic brain injuries and the like, and has a broad application prospect.
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- (2,4-dihydroxy-5-isopropylphenyl)(4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)ketone derivative, preparation and uses thereof
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The present invention discloses a (2,4-dihydroxy-5-isopropylphenyl)(4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)ketone derivative, preparation and uses thereof, and particularly relates to a (2,4-dihydroxy-5-isopropylphenyl)(4,6-dihydro-5H-thieno[2,3-c]pyrrol
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Paragraph 0103; 0104; 0105
(2016/10/08)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides a compound for use in medicine, the compound being a compound of the formula (VI0) or a salt, solvate, tautomer or N-oxide thereof: wherein the bicyclic group: is selected from the structures C1, C5 and C6: wherein n is 0, 1, 2 or 3; R1 is hydrogen, hydroxy, or O—Rz; R2a is hydroxy, methoxy or O—Rz; provided that at least one of R1 and R2a is O—Rz; Rz is Lp-Rp1; SO3H; a glucuronide residue; a mono-, di- or tripeptide residue; or Lp is a bond, C═O, (C═O)O, (C═O)NRp1 or S(O)xNRp1; x is 1 or 2; Rp1 is hydrogen or a an optionally substituted C1-25 hydrocarbyl group containing 0, 1 or 2 carbocyclic rings and 0, 1, 2, 3, 4, 5 or 6 carbon-carbon multiple bonds, provided that Rp1 is not hydrogen when Lp is a bond, C═O or (C═O)O; and provided also that O—Rz does not contain an O—O moiety; and excluding compounds wherein R1 is hydroxy and R2a is methoxy; Rp2 and Rp3 are the same or different and each is a group Rp1; and R3, R4a, R8 and R10 are defined in the claims. The compounds of formula (VI0) are pro-drugs of parent compounds wherein R1 and/or R2a are hydroxy, wherein the parent compounds have Hsp90 inhibiting activity.
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Page/Page column 100
(2010/06/22)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides a compound of the formula (1 ): or a salt, solvate, N-oxide or tautomer thereof; wherein either R1 is R1a and R2 is R2a; or R1 is R1b and R2 is R2b; provided that in each case at least one of R1 and R2 is other than hydrogen; R1a and R2a are the same or different and each is selected from hydrogen, C1-4 alkyl, C2-4 alkenyl and C2-4 alkynyl wherein the C1-4 alkyl is optionally substituted by C1-2 alkoxy; R1b and R2b are the same or different and are selected from hydrogen, C(O)NR4R5, C(O)R6 and C(O)OR6 where R6 is C1-4 alkyl, R4 and R5 are both C1-4 alkyl, or NR4R5 forms a 4 to 7 membered saturated heterocyclic ring optionally containing a second heteroatom ring member selected from O, N or S and oxidised forms of N and S, the heterocyclic ring being optionally substituted by one or two C1-4 alkyl groups and/or one or two oxo groups; and R3 is a group (D): wherein the asterisk denotes the point of attachment to the isoindoline ring; but excluding acetic acid 5-acetoxy-4-isopropyl-2-[5-(4-methyl-piperazin-1 -ylmethyl)-1,3- dihydro-isoindole-2-carbonyl]-phenyl ester.
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Page/Page column 106
(2009/11/29)
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1- 5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 inhibitors.
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Page/Page column 240
(2008/06/13)
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase inhibitors.
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Page/Page column 262
(2008/06/13)
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase and/or aurora kinase inhibitors.
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Page/Page column 314-315
(2008/06/13)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides the use of a compound for the manufacture of a medicament for the treatment of pain, wherein the compound is a compound of the formula (Vl): or a salt, solvate, tautomer or N-oxide thereof; wherein the bicydic group: is selected from the structures C1, C5 and C6: wherein n, R1, R2a, R3, R4a, R8 and R10 are as defined in the claims. The invention also provides the use of a compound of the formula (Vl) for the manufacture of a medicament for the prophylaxis or treatment of a fungal, protozoal, viral or parasitic disease state or condition (other than a disease state or condition due to Plasmodium falciparum) or for use in the prophylaxis or treatment of Ewing's sarcoma, atherosclerosis or lupus erythematosus
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Page/Page column 158
(2008/06/13)
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