WO2001017984A1 - Chalcone coumarins - Google Patents

Chalcone coumarins Download PDF

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Publication number
WO2001017984A1
WO2001017984A1 PCT/EP2000/008367 EP0008367W WO0117984A1 WO 2001017984 A1 WO2001017984 A1 WO 2001017984A1 EP 0008367 W EP0008367 W EP 0008367W WO 0117984 A1 WO0117984 A1 WO 0117984A1
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WO
WIPO (PCT)
Prior art keywords
methyl
group
vib
coumarin
compound according
Prior art date
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Ceased
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PCT/EP2000/008367
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English (en)
French (fr)
Inventor
Ezio Bombardelli
Piero Valenti
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Indena SpA
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Indena SpA
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Filing date
Publication date
Priority to SI200030111T priority Critical patent/SI1212311T1/xx
Priority to EP00965902A priority patent/EP1212311B1/en
Priority to AU76488/00A priority patent/AU775083B2/en
Priority to PL00353245A priority patent/PL353245A1/xx
Priority to JP2001521731A priority patent/JP2003508523A/ja
Priority to CA002382112A priority patent/CA2382112A1/en
Priority to DK00965902T priority patent/DK1212311T3/da
Priority to SK310-2002A priority patent/SK3102002A3/sk
Priority to DE60001850T priority patent/DE60001850T2/de
Priority to HK02105581.2A priority patent/HK1043997B/en
Application filed by Indena SpA filed Critical Indena SpA
Priority to AT00965902T priority patent/ATE235480T1/de
Publication of WO2001017984A1 publication Critical patent/WO2001017984A1/en
Priority to US10/075,625 priority patent/US6767916B2/en
Priority to NO20021048A priority patent/NO20021048L/no
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A61K31/37—Coumarins, e.g. psoralen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/18—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted otherwise than in position 3 or 7
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the present invention relates to a novel class of compounds which have structures related to certain naturally occurring and synthetic chalcones, as well as to methods for the preparation of such compounds and to pharmaceutical uses thereof.
  • the compound 1 ,3-diphenyl-2-propene-1 -one is known by the trivial name chalcone.
  • Many naturally occurring flavonoids share structural features with chalcone and are referred to by the generic term "chalcones" .
  • certain flavonoids, including ones which are also classified as chalcones have recently been demonstrated to have anticancer activity (Cancer Research 48, 5754, 1 988) and chemopreventive activity in some tumours (J. Nat. Prod. 53, 23, 1990).
  • Patent Publication No. WO 91 17749 and in International Patent Publication No. WO 96/19209 (Baylor College of Medicine) have proved to have a significant antiproliferation activity on a variety of different cell lines.
  • Ar represents: a substituted or unsubstituted, (preferably aromatic), carbocyclic or heterocyclic group, said carbocyclic or heterocyclic group containing from 5 to 10 ring atoms, said ring atoms forming one or two rings, wherein the or each ring contains 5 or 6 ring atoms, any heteroatoms being selected from N, O and S, any substituents on the Ar group being independently selected from the group consisting of:
  • R represents
  • R 0 and R 1 are as defined above; and R 1 represents H or a lower C ⁇ straight or branched hydrocarbyl group which may be unsubstituted or substituted by 1 , 2 or 3 substituents selected from Cl, Br, F, OMe, NO 2 and CF 3 .
  • a preferred class of compounds of Formula (I) are those wherein Ar represents a substituted or unsubstituted (preferably aromatic), heterocyclic group said heterocyclic group containing from 5 to 10 ring atoms, said ring atoms forming one or two rings, wherein the or each ring contains 5 or 6 ring atoms, the heteroatoms being selected from N, O and S, and any substituents on the Ar group being independently selected from the group consisting of:
  • R 10 represents a saturated or unsaturated lower G, ⁇ straight or branched hydrocarbyl group which may be unsubstituted or substituted by 1, 2 or 3 substituents selected from:
  • R 1 represents a saturated or unsaturated lower C ⁇ straight or branched hydrocarbyl group or a phenyl group.
  • Ar contains a basic nitrogen function, for example, by virtue of a heterocyclic nitrogen ring atom being present, or Ar may contain a substituent having a basic nitrogen, such as an amine, or an acetamido function.
  • the Ar group is preferably a substituted or unsubstituted (preferably aromatic), heterocyclic group, said heterocyclic group containing from 5 to 10 ring atoms, wherein at least one of the ring atoms is a nitrogen atom and any substituent on the ring is as defined as for Formula (I).
  • Particularly preferred Ar groups include pyridyl or indolyl.
  • a second preferred group of compounds of Formula (I) are those wherein Ar represents a substituted or unsubstituted (preferably aromatic), carbocyclic group, said carbocyclic group containing from 5 to 10 ring atoms, said ring atoms forming one or two rings, wherein the or each ring contains 5 or 6 ring atoms, and any substituents on the Ar group being independently selected from the group consisting of:
  • any substituents on the Ar group are preferably selected from the group consisting of: NHCOCH 3 , N(R 6 )(R 8 ), OR 10 and -OCOR 11 , wherein R 6 , R 8 , R 10 and R 11 are as defined as above for Formula (I).
  • R 10 and R 11 preferably represent a saturated or unsaturated C, ⁇ straight chain or branched hydrocarbyl group, in particular methyl, ethyl, n-propyl or isopropyl.
  • Ar is preferably substituted with one or more OR 10 groups, wherein R 10 represents a saturated or unsaturated lower C, ⁇ straight or branched hydrocarbyl group.
  • R 10 represents a saturated or unsaturated lower C, ⁇ straight or branched hydrocarbyl group.
  • An especially preferred R 0 group is methyl.
  • Particularly preferred Ar groups include phenyl or phenyl substituted with 1 , 2 or 3 methoxy groups.
  • the basic nitrogen function is provided by virtue of the carbocyclic ring comprising at least one substituent selected from NHCOCH 3 or N(R 6 )(R 8 ), wherein R 6 and R 8 are as defined as for Formula (I).
  • R preferably represents an unsaturated lower C ⁇ straight or branched hydrocarbyl group.
  • R 1 preferably represents a lower C ⁇ straight or branched hydrocarbyl group, especially methyl.
  • a further group of preferred compounds of Formula (I) include those wherein:
  • Ar represents phenyl, which may be unsubstituted or substituted by one, two or three substituents independently selected from
  • R represents
  • the present invention also provides the use of a compound of Formula (I) in the manufacture of an antiproliferative medicament.
  • the compounds of the present invention may be useful for the manufacture of a medicament for the treatment or prevention of neoplasms, particularly those located in the uterus, ovary or breast.
  • the compounds may be useful for the manufacture of a medicament for the treatment of cancer cells that are resistant to paclitaxel and docetaxel.
  • the compounds of Formula (I) may advantageously be used in combination therapies involving the combined use of a compound of Formula (I) and another anti-neoplastic agent, especially paclitaxel or docetaxel.
  • the combination therapy may involve simultaneous or successive administration of a compound of Formula (I) and an anti- neoplastic agent. Such combination therapy forms a further aspect of the invention.
  • the compounds of the invention may be further used in the manufacture of a medicament for the treatment or prevention of menopausal disorders and osteoporosis.
  • the present invention further includes a pharmaceutical composition comprising one of more of the compounds of Formula (I) in combination with one or more pharmaceutically acceptable excipients.
  • a solution of KOH 50% (3 ml) is added to an equimolar solution of a ketone (0.0075 mol) and an aldehyde (0.0075 mol) in ethanol 95 %; the addition is performed under energetic stirring at room temperature.
  • the reaction is left under stirring for one night and then diluted with water and acidified.
  • the precipitate is separated by filtration and dried under vacuum.
  • the compounds are crystallized by ethanol or first separated by chromatography and then crystallized by ethanol .
  • Example 4 1 -[4-Methyl-7-(3-methylbut-2-enyloxy)coumarin-8-yl]-3-(3 f 4,5-tri- methoxyphenyl)propen-1 -one (see accompanying formula drawing VIB 120).
  • a solution of KOH 50% (3 ml) is added to an equimoiar solution of 4-methyl-7- methylallyloxy-8-acetylcoumarin (2.04 g, 0.0075 mol) and benzaldehyde (0.8 g, 0.0075 mol) in ethanol 95%; the addition is performed under energetic stirring at room temperature. The reaction is left under stirring for one night and then diluted with water and acidified. The precipitate is separated by filtration and dried under vacuum.
  • Example 7 1 -[4-Methyl-7-(2-methylallyloxy)coumarin-8-yl]-3-(3-methoxy-phenyD- propen-1-one (see accompanying formula drawing VIB 162).
  • a solution of KOH 50% (3 ml) is added to an equimoiar solution of 4-methyl-7- methylallyloxy-8-acetylcoumarin (2.04 g, 0.0075 mol) and 3-methoxybenzaldehyde (1 .01 g, 0.0075mol) in ethanol 95%; the addition is performed under energetic stirring at room temperature.
  • the reaction is left under stirring for one night and then diluted with water and acidified.
  • the precipitate is separated by filtration and dried under vacuum.
  • Example 8 1 -[4-Methyl-7-(2-methylallyloxy)coumarin-8-yl]-3-(3,4,5-trimethoxy- phenyl)-propen-1 -one (see accompanying formula drawing VIB 1 23).
  • Example 10 1 -[4-Methyl-7-(allyloxy)coumarin-8-yl]-3-(pyridin-3-yl)-propen-1 -one. (see accompanying formula drawing VIB 161 ).
  • Example 1 1 . 1 - [4-Methyl-7-(allyloxy)coumarin-8-yl] -3-(3-methoxyphenyl)-propen-
  • a solution of KOH 50% (3 ml) is added to an equimoiar solution of 4-methyl-7- allyloxy-8-acetylcoumarin (1 .93 g, 0.0075 mol) and 3-methoxybenzaldehyde ( 1 .01 g, 0.0075 mol) in ethanol 95 %; the addition is performed under energetic stirring at room temperature.
  • the reaction is left under stirring for one night and then diluted with water and acidified.
  • the precipitate is separated by filtration and dried under vacuum.
  • the compound is crystallized by methanol to give 1 .6 g of product m.p.
  • Example 12 1 -[4-Methyl-7-(allyloxy)coumarin-3-yl]-3-(3,4,5-trimethoxyphenyD- propen-1 -one (see accompanying formula drawing VIB 160).
  • a solution of KOH 50% (3 ml) is added to an equimoiar solution of 4-methyl-7- allyloxy-8-acetylcoumarin (1 .93 g, 0.0075 mol) and 3-methoxybenzaldehyde ( 1 .47 g, 0.0075 mol) in ethanol 95%; the addition is performed under energetic stirring at room temperature.
  • the reaction is left under stirring for one night and then diluted with water and acidified.
  • the precipitate is separated by filtration and dried under vacuum.
  • Example 14 1 -[4-Methyl-7-(prop-2-ynyloxy)coumarin-8-yl]-3-phenylpropen-1 -one (see accompanying formula drawing VIB 124).
  • Example 15 1 -[4-Methyl-7-(prop-2-ynyioxy)coumarin-8-yl]-3-(pyridin-3-yl)-propen-1 - one (see accompanying formula drawing VIB 125).
  • Example 16 1 -[4-Methyl-7-(prop-2-ynyloxy)coumarin-8-yl]-3-(3-methoxyphenyl)- propen-1-one (see accompanying formula drawing VIB 163).
  • Example 20 1 -[4-Methyl-7-(allyloxy)coumarin-8-yl]-3-(2,6-dichloro-phenyl)-propen- 1-one (see accompanying formula drawing VIB 243).
  • the compounds were then evaluated in combination with paclitaxel for their cytostatic activity against the drug-resistant breast cancer cells MDA-435/LCC6-MDR.
  • the compounds were used in combination with paclitaxel, the paclitaxel being at a concentration of 0.1 ⁇ M, the ICg, of paclitaxel decreases by 3-5 fold when used in combination with each of compounds VIB 106 and VIB 122, i.e. from 426 n to 130-86 nM compared with paclitaxel alone. Consequently, in the presence of these compounds, paclitaxel can recover its excellent inhibitory activities against the drug- resistant cancer cells.
  • the treatment consisted of concurrent exposure of MDA-435/LCC-MDR cells to paclitaxel in the presence or absence of the compounds reversing agent (1 ⁇ M)for 72 h in vitro.
  • Assessment of cytotoxicity i.e. cell growth inhibition, was determined according to the methods of Skehan, et al. as discussed in J. Nat. Cancer Inst., 82, 1107, 1990. Briefly, cells were plated between 400 and 1200 cells/well in 96 well plates and incubated at 37°C for 15-18 h prior to drug addiction to allow attachment of cells. Compounds were solubilized in 100% DMSO and further diluted in RPMI-1640 containing 10 mM HEPES.
  • SRB Sulforhodamine B

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • Orthopedic Medicine & Surgery (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • General Preparation And Processing Of Foods (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
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PCT/EP2000/008367 1999-09-03 2000-08-28 Chalcone coumarins Ceased WO2001017984A1 (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
DE60001850T DE60001850T2 (de) 1999-09-03 2000-08-28 Chalcon coumarine
AU76488/00A AU775083B2 (en) 1999-09-03 2000-08-28 Chalcone coumarins
PL00353245A PL353245A1 (en) 1999-09-03 2000-08-28 Chalcone coumarins
JP2001521731A JP2003508523A (ja) 1999-09-03 2000-08-28 カルコンクマリン類
CA002382112A CA2382112A1 (en) 1999-09-03 2000-08-28 Chalcone coumarins
DK00965902T DK1212311T3 (da) 1999-09-03 2000-08-28 Chalconcumariner
SK310-2002A SK3102002A3 (en) 1999-09-03 2000-08-28 Chalcone coumarins, pharmaceutical composition comprising them and their use
SI200030111T SI1212311T1 (en) 1999-09-03 2000-08-28 Chalcone coumarins
EP00965902A EP1212311B1 (en) 1999-09-03 2000-08-28 Chalcone coumarins
HK02105581.2A HK1043997B (en) 1999-09-03 2000-08-28 Chalcone coumarins
AT00965902T ATE235480T1 (de) 1999-09-03 2000-08-28 Chalcon coumarine
US10/075,625 US6767916B2 (en) 1999-09-03 2002-02-15 Chalcone coumarins
NO20021048A NO20021048L (no) 1999-09-03 2002-03-01 Chalkonkumariner

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9920908.2A GB9920908D0 (en) 1999-09-03 1999-09-03 Chalcone coumarins
GB9920908.2 1999-09-03

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US10/075,625 Continuation US6767916B2 (en) 1999-09-03 2002-02-15 Chalcone coumarins

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PCT/EP2000/008367 Ceased WO2001017984A1 (en) 1999-09-03 2000-08-28 Chalcone coumarins

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US (1) US6767916B2 (enExample)
EP (1) EP1212311B1 (enExample)
JP (1) JP2003508523A (enExample)
KR (1) KR100819574B1 (enExample)
CN (1) CN1142927C (enExample)
AT (1) ATE235480T1 (enExample)
AU (1) AU775083B2 (enExample)
CA (1) CA2382112A1 (enExample)
CZ (1) CZ2002786A3 (enExample)
DE (1) DE60001850T2 (enExample)
DK (1) DK1212311T3 (enExample)
ES (1) ES2191643T3 (enExample)
GB (1) GB9920908D0 (enExample)
HK (1) HK1043997B (enExample)
HU (1) HUP0202581A3 (enExample)
NO (1) NO20021048L (enExample)
PL (1) PL353245A1 (enExample)
PT (1) PT1212311E (enExample)
RU (1) RU2266291C2 (enExample)
SE (1) SE1212311T5 (enExample)
SK (1) SK3102002A3 (enExample)
WO (1) WO2001017984A1 (enExample)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7329687B2 (en) 2002-04-18 2008-02-12 Sri International Flavanoid compounds as chemotherapeutic, chemopreventive, and antiangiogenic agents
WO2009036656A1 (fr) * 2007-09-18 2009-03-26 Nanjing Zhongrui Medicine Co., Ltd Dérivés de coumarine, leurs procédés de préparation et leurs utilisations
US7638554B2 (en) 2002-04-18 2009-12-29 Sri International Flavanoids as chemotherapeutic, chemopreventive, and antiangiogenic agents
US8067461B2 (en) 2005-06-08 2011-11-29 Temple University-Of The Commonwealth System Of Higher Education 3-acyl coumarins, thiochromones and quinolones and therapeutic uses thereof
WO2012017454A1 (en) 2010-08-05 2012-02-09 Council Of Scientific & Industrial Research Coumarin-chalcones as anticancer agents
CN109293616A (zh) * 2018-09-29 2019-02-01 贵州大学 一种含香豆素查尔酮类衍生物、其制备方法及应用
US11400090B2 (en) 2017-11-16 2022-08-02 The Institute Of Cancer Research: Royal Cancer Hospital Coumarin derivative for therapy or prophylaxis of a cell proliferative disorder
US11517573B2 (en) 2019-09-13 2022-12-06 The Institute Of Cancer Research: Royal Cancer Hospital Therapeutic compositions, combinations, and methods of use
US11873296B2 (en) 2022-06-07 2024-01-16 Verastem, Inc. Solid forms of a dual RAF/MEK inhibitor

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CN101041646B (zh) * 2007-04-30 2011-07-20 浙江大学 含氮查耳酮衍生物的制备方法和用途
WO2009060835A1 (ja) * 2007-11-05 2009-05-14 Kyoto University 新規ユビキリン結合性小分子
EP3333153A1 (en) 2011-06-15 2018-06-13 The U.S.A. as represented by the Secretary, Department of Health and Human Services Nuclear receptor modulators and their use for the treatment and prevention of cancer
CN103420990B (zh) * 2012-05-23 2016-04-20 复旦大学 7-氧、硫或氮杂取代香豆素及其衍生物和用途
CN102731457A (zh) * 2012-06-25 2012-10-17 西南石油大学 一种水溶性荧光示踪聚合物及其制备方法

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FR2387956A1 (fr) * 1977-04-20 1978-11-17 Unicler Derives de la pyridine et leur preparation
WO1991017749A1 (en) * 1990-05-17 1991-11-28 Baylor College Of Medicine Growth inhibitors and methods of treating cancer and cell proliferative diseases
WO1995018803A1 (en) * 1994-01-07 1995-07-13 Allergan Acetylenes disubstituted with a phenyl or heteroaryl group and a 2-oxochromanyl, 2-oxothiochromanyl or 2-oxo-1,2,3,4-tetrahydroquinolinyl group having retinoid-like activity
WO1996019209A1 (en) * 1994-12-20 1996-06-27 Indena S.P.A. Chalcones and esters thereof with antiproliferative activity in uterus, ovary and breast tumours
WO1996022985A1 (en) * 1995-01-24 1996-08-01 Warner-Lambert Company 2-(2-amino-3-methoxyphenyl)-4-oxo-4h-[1]benzopyran for treating proliferative disorders

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Publication number Priority date Publication date Assignee Title
FR2387956A1 (fr) * 1977-04-20 1978-11-17 Unicler Derives de la pyridine et leur preparation
WO1991017749A1 (en) * 1990-05-17 1991-11-28 Baylor College Of Medicine Growth inhibitors and methods of treating cancer and cell proliferative diseases
WO1995018803A1 (en) * 1994-01-07 1995-07-13 Allergan Acetylenes disubstituted with a phenyl or heteroaryl group and a 2-oxochromanyl, 2-oxothiochromanyl or 2-oxo-1,2,3,4-tetrahydroquinolinyl group having retinoid-like activity
WO1996019209A1 (en) * 1994-12-20 1996-06-27 Indena S.P.A. Chalcones and esters thereof with antiproliferative activity in uterus, ovary and breast tumours
WO1996022985A1 (en) * 1995-01-24 1996-08-01 Warner-Lambert Company 2-(2-amino-3-methoxyphenyl)-4-oxo-4h-[1]benzopyran for treating proliferative disorders

Non-Patent Citations (4)

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Title
AHLUWALIA, V. K. ET AL: "New route to synthesis of some 8-(dihydrocinnamoyl)dihydrocoumarin derivatives", INDIAN J. CHEM., SECT. B (1988), 27B(1), 70-1, XP000979595 *
KHAN, M. S. Y. ET AL: "Synthesis of new.alpha.-pyronoflavones and related products. Part II", INDIAN J. CHEM., SECT. B (1993), 32B(8), 817-21, XP000981909 *
SANGWAN, NARESH K. ET AL: "Synthesis and biological properties of substituted 2H-1-benzopyran-2-ones and 2H,10H-benzo[1,2-b:3,4-b']dipyran-2,10- diones", J. PRAKT. CHEM. (1988), 330(1), 137-41, XP000979579 *
SHARAN, P. ET AL: "Synthesis of some 7-hydroxy-4-methylcoumarin-8-yl chalcones and related isoxazoles as potential fungicides", J. INDIAN CHEM. SOC. (1989), 66(6), 393-4, XP000979582 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7638554B2 (en) 2002-04-18 2009-12-29 Sri International Flavanoids as chemotherapeutic, chemopreventive, and antiangiogenic agents
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RU2266291C2 (ru) 2005-12-20
CN1371370A (zh) 2002-09-25
SK3102002A3 (en) 2003-10-07
SE1212311T5 (enExample) 2003-06-10
DE60001850D1 (de) 2003-04-30
US6767916B2 (en) 2004-07-27
DE60001850T2 (de) 2003-12-11
CN1142927C (zh) 2004-03-24
HUP0202581A3 (en) 2003-07-28
SE1212311T3 (enExample) 2003-05-06
JP2003508523A (ja) 2003-03-04
HK1043997B (en) 2003-08-15
PT1212311E (pt) 2003-08-29
KR20020030800A (ko) 2002-04-25
EP1212311B1 (en) 2003-03-26
KR100819574B1 (ko) 2008-04-04
DK1212311T3 (da) 2003-06-23
ATE235480T1 (de) 2003-04-15
GB9920908D0 (en) 1999-11-10
PL353245A1 (en) 2003-11-03
RU2002108567A (ru) 2004-01-10
ES2191643T3 (es) 2003-09-16
NO20021048D0 (no) 2002-03-01
HUP0202581A2 (hu) 2002-11-28
US20020161036A1 (en) 2002-10-31
HK1043997A1 (en) 2002-10-04
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EP1212311A1 (en) 2002-06-12
CA2382112A1 (en) 2001-03-15

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