WO2006097617A2 - Nouveaux derives dihydropyrimidines et leur utilisation comme agents anti-cancereux - Google Patents
Nouveaux derives dihydropyrimidines et leur utilisation comme agents anti-cancereux Download PDFInfo
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- WO2006097617A2 WO2006097617A2 PCT/FR2006/000556 FR2006000556W WO2006097617A2 WO 2006097617 A2 WO2006097617 A2 WO 2006097617A2 FR 2006000556 W FR2006000556 W FR 2006000556W WO 2006097617 A2 WO2006097617 A2 WO 2006097617A2
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- 0 C[*-](C)*(C)=C1C=CC(CCC(O)=O)=CC1 Chemical compound C[*-](C)*(C)=C1C=CC(CCC(O)=O)=CC1 0.000 description 3
- RQOPYBJYXDKFSB-UHFFFAOYSA-N CC(NC(NC1c2cc(O)ccc2)=S)=C1C(c1ccccc1)=O Chemical compound CC(NC(NC1c2cc(O)ccc2)=S)=C1C(c1ccccc1)=O RQOPYBJYXDKFSB-UHFFFAOYSA-N 0.000 description 1
- ITJAYNBNCHZDKC-UHFFFAOYSA-N CC(NC(NC1c2cccc(O)c2)=S)=C1C(c1cc(Cl)ccc1)=O Chemical compound CC(NC(NC1c2cccc(O)c2)=S)=C1C(c1cc(Cl)ccc1)=O ITJAYNBNCHZDKC-UHFFFAOYSA-N 0.000 description 1
- PFCVYLRQXLAEIE-UHFFFAOYSA-N CC(NC(NC1c2cccc(O)c2)=S)=C1C(c1cc(I)ccc1)=O Chemical compound CC(NC(NC1c2cccc(O)c2)=S)=C1C(c1cc(I)ccc1)=O PFCVYLRQXLAEIE-UHFFFAOYSA-N 0.000 description 1
- LZMVHFLNMWWPLI-UHFFFAOYSA-N CC(NC(NC1c2cccc(O)c2)=S)=C1C(c1cccc(F)c1)=O Chemical compound CC(NC(NC1c2cccc(O)c2)=S)=C1C(c1cccc(F)c1)=O LZMVHFLNMWWPLI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- the present invention relates to novel molecules derived from dihydropyrimidine, the drugs comprising them and their use as anti-cancer agents.
- Eg5 which belongs to the kinesin family of motor proteins involved in cell proliferation, is one of these proteins.
- an inhibitory molecule of Eg5 is likely to be active in anticancer therapy.
- Monastrol is weak (II 50 > 14 ⁇ m) and can not be considered for use as an anti-cancer treatment.
- the compounds of the present invention are endowed with modulator activity of Eg5 protein, in particular an inhibitory activity of Eg5 protein. They have an antimitotic effect and as such can be used for the preparation of a medicament for the prevention or treatment of cancer.
- the invention relates more particularly to the molecules corresponding to formula (I):
- X represents an atom selected from: O and S;
- R 1 represents a group chosen from: a hydrogen atom, an alkyl group in C 1 -C 6 alkenyl, C 2 -C 6 haloalkyl, C 1 -C 6 aralkyl, C 6 -CJ 2, phenyl optionally substituted by one or more groups chosen from: a halogen, a C 1 -C 3 alkyl, a C 1 -C 3 haloalkyl, a hydroxyl group or a C 1 -C 3 alkoxy group;
- R 2 represents a group selected from: alkyl C 1 -C 6 alkenyl, C 2 -C 6 haloalkyl, C 1 -C 6 aralkyl, C 6 -C 12 phenyl optionally substituted with one or more groups selected from: halogen, C 1 -C 3 -haloalkyl-C 3, a hydroxyl group, an alkoxy group of C 1 -C 3 alkyl;
- R 3 represents a group chosen from:
- Y 1 represents a group chosen from: a group -Q 1 , a group -OQ 1 , a group -NHQi, a group - NQ 1 Q 2 ;
- O w Y 2 and Y 2 represents a group selected from: H, -Q 2 group, a group -OCOQ:
- Y 7 represents a group chosen from: H and a group -Q 1 ; and either
- Y 5 represents a group selected from H and a group - Q 2
- Y 6 is selected from: a hydrogen atom and a group selected from: -Qs - COQ 3, -CO 2 Q 3; is
- Y 5 is H, and Y 6 is selected from -SO 2 Q 3, - CONHQ 3;
- Y 8 and Y 8 is selected from one of the following groups: -Q 1 - OQ 1 -OCONHQ 1 -OCONQ 1 Q 2, -NHQ 1, -NQ 1 Q 2, -NHCOQ 1 -NQ 1 COQ 2 , -NQiCO 2 Q 2 , -NHCO 2 Q 1 , -NHSO 2 Q 1 , -NHCONHQ 1 ; and Q 1 , Q 2 and Q 3 , which may be identical or different, represent a group chosen from: a C 1 -C 6 alkyl, C 2 -C 6 alkenyl and haloalkyl group;
- C 1 -C 6 alkyl denotes a linear, branched or cyclic hydrogen-carbon radical comprising from 1 to 6 carbon atoms; we can mention by methyl, propyl, n-butyl, isopropyl, isobutyl, terbutyl, n-pentyl, hexyl, isohexyl, 1-ethylpropyl, etc.
- C 2 -C 6 alkenyl denotes a linear, branched or cyclic hydrogenated hydrocarbon radical containing at least one double bond and 2 to 6 carbon atoms.
- propene-2-yl may be mentioned.
- aralkyl denotes a linear, branched or cyclic alkyl radical substituted with an aryl group, such as for example a pyridine or a phenyl, itself optionally substituted with one or more groups chosen from: a halogen, a C 1 -alkyl 1 -C 3 , a C 1 -C 3 haloalkyl, a hydroxyl group, a C 1 -C 3 alkoxy group.
- halo C 1 -C 6 denotes an alkyl radical in C1-C 6 linear, branched or cyclic substituted by at least one halogen atom such as F, Br, I, Cl can be cited for example:. - CF 3 , -CH 2 -CH 2 Cl.
- the halogen atom can be chosen from the following list: F, Cl, Br, I.
- the C 1 -C 6 alkoxy group denotes a radical -OW in which W represents a C 1 -C 6 alkyl. There may be mentioned for example a methoxy radical, ethoxy isoproproxy.
- the acyloxy group C 1 -C n denotes a radical -O (CO) W in which W represents a C 1 -C 2 alkyl.
- W represents a C 1 -C 2 alkyl.
- an acetyl radical may be mentioned.
- the heteroatoms may be chosen preferentially from S, N or O. Examples that may be mentioned include pyridine, quinoline and heteronaphthyl groups.
- R 2 is selected from alkyl groups Cj-C 6 haloalkyl and C 1 -C 6 alkyl.
- R 2 may be chosen from: -CH 3 , -CH 2 -CH 3 , -CH (CH 2 ) 2 , -CH 2 -CH (CH 3 ) 2 , -CF 3 .
- the group Y may be any one of Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , that is to say that it may be in the ortho, meta or para position on the aromatic ring.
- Y is chosen from: -OH, H, Cl, F, Br, -OCH 3 .
- Z 1 , Z 3 , Z 4 , Z 5 ) (H, H, H, H) and Z 2 represents a group chosen from a hydroxyl group and a C 1 -C 6 alkoxy group.
- the invention relates to the molecules of formula (I) wherein R 1 represents a group selected from: alkyl C 1 -C 6 alkenyl, C 2 -C 6 haloalkyl, C 1 - C 6 , phenyl optionally substituted by one or more groups chosen from: a halogen, a C 1 -C 3 alkyl, a C 1 -C 3 haloalkyl, a hydroxyl group or a C 1 -C 3 alkoxy group.
- R 1 represents a group selected from: alkyl C 1 -C 6 alkenyl, C 2 -C 6 haloalkyl, C 1 - C 6 , phenyl optionally substituted by one or more groups chosen from: a halogen, a C 1 -C 3 alkyl, a C 1 -C 3 haloalkyl, a hydroxyl group or a C 1 -C 3 alkoxy group.
- R 1 is selected from C 1 -C 3 alkyls and alkenyls.
- R 3 is advantageously chosen from
- R 3 is chosen
- the phenyl group is advantageously substituted by one or more substituents chosen from: OCH 3 , -F, -Cl, -Br.
- Q 1 Y 1 is chosen from methyl, phenyl, meta-fluorophenyl, meta-iodophenyl, meta-chlorophenyl and meta-methoxyphenyl.
- the compounds of the invention are chosen from those numbered 1 to 34 and whose formula is given below:
- the three reagents (II), (III) and (IV) are reacted in the absence of solvent.
- the aldehyde (II) and the ketone (III) are in an amount substantially equivalent in number of moles, while the thiourea (IV) is present in excess.
- thiourea (IV) is used in an amount of between 1 and 2 times the amount of aldehyde (II) or ketone (III).
- the mixture is heated to a temperature ranging from 80 to 120 ° C. for several hours.
- a catalyst may optionally be employed. This catalyst may for example be chosen from Yb (OTF) 3 , Sc (OTf) 3 , La (OTf) 3 , YbCl 3 , InCl 3 , concentrated HCl.
- the resulting product is purified by methods well known to those skilled in the art: crystallization, precipitation, silica gel chromatography, extraction, high performance liquid chromatography.
- the reaction described in scheme 1 can be carried out in solid phase, the compound (II) being attached to a solid resin by one of its functionalities Z 1 , Z 2 , Z 3 , Z 4 or Z 5 .
- Z 4 OH
- the compound (II) is grafted onto a carboxylic acid-functional resin by an esterification reaction to give the functionalized resin (Ilbis).
- This resin (Ilbis) is placed in the presence of the ketone (III) and the thiourea (IV) to give the grafted resin (Ibis) from which the compound (I) can be removed by simple hydrolysis.
- the grafting of (II) on the acidic resin is done using a coupling agent such as DCC.
- a coupling agent such as DCC.
- the reaction of the grafted resin (Ilbis) with ketone (III) and thiourea (IV) is as described above without solvent, at a temperature between 80 and 120 ° C in the presence of a catalyst and / or by applying a treatment with microwaves.
- a catalyst can for example be chosen from Yb (OTF) 3 , Sc (OTf) 3 , La (OTf) 3 , YbCl 3 , InCl 3 , concentrated HCl.
- the invention further relates to a medicament comprising a compound of formula (I) as described above in a pharmaceutically acceptable carrier.
- the compounds of the invention and the medicaments comprising them are more particularly intended for the prevention and / or treatment of a proliferative disease such as cancer.
- These compounds and these drugs have the property of modulating the activity of the Eg5 motor protein and / or of inducing apoptosis. They have an antimitotic activity and therefore, they can be used for the prevention and / or the treatment of various proliferative-type pathologies such as cancers, autoimmune diseases, viral diseases, fungal diseases, neurological diseases. degenerative and cardiovascular diseases.
- the molecules and medicaments of the invention are particularly useful for the prevention and / or treatment of cancers, in particular: cancer of the lung, breast, pancreas, stomach, ovaries, esophagus, thyroid, prostate, melanomas, lymphomas, sarcomas, carcinomas, tumors of the nervous system.
- the proliferative diseases include adenomatous polyposis, atherosclerosis.
- Viral diseases include infection with HIV, herpes.
- Autoimmune diseases include inflammatory bowel diseases, psoriasis, autoimmune diabetes.
- Neurodegenerative diseases include Alzheimer's disease, Parkinson's disease.
- the invention further relates to the use of a compound of formula (I) as described above for the preparation of a medicament for the prevention and / or treatment of a proliferative disease such as cancer .
- the molecules of the invention are also useful for blocking the development of cancer, in particular by blocking the progression of malignant cells or by inhibiting the development of the tumor.
- the compounds and medicaments of the invention may be used alone or in combination with another molecule or drug known as anticancer treatment such as for example doxorubicin, paclitaxel, etoposide, cisplatin, tamoxifen, methotrexate , 5-fluorouracyl.
- anticancer treatment such as for example doxorubicin, paclitaxel, etoposide, cisplatin, tamoxifen, methotrexate , 5-fluorouracyl.
- the amount of molecule of formula (I) to be administered to humans, or possibly to the animal, depends on the activity specific to this molecule, an activity which can be measured by means that will be exposed in the examples. It also depends on the degree of severity of the pathology to be treated, the age and weight of the individual.
- the reagents used are commercial products. Spectra
- ADVANCE400 400 Mhz. The chemical shifts are given in ppm ( ⁇ ), tetramethylsilane being used as a reference. HPLC-mass analyzes were performed on a Waters® device with UV detection and light scattering (DEDL).
- a mixture of aldehyde (Immole), ⁇ -keto ester or ⁇ -diketone (Immole) and thiourea (1.5 mmol) are heated to 0 ° C. without stirring for 3.5 hours.
- a catalyst, ytterbium triflate is employed in an amount of 5 mol%.
- the product obtained is isolated by one of the following methods: The mixture is allowed to cool to room temperature. It is added ether (4ml). The resulting solid is filtered, washed with ether (2x1 ml) and then with water (2x1 ml) and dried.
- the resin is swollen in dry THF (4 mL) and a suspension of K 2 CO 3 (6 eq) in methanol (2 mL) is added. The mixture is stirred at room temperature for several hours and the resin is filtered, washed twice with methanol. The crude material is then adsorbed on silica and purified by filtration on a silica micro-column (1 g of silica) with a solvent gradient of a hexane / Et 2 ⁇ 7/3 to Et 2 O mixture (method purification d).
- ATPase levels were measured using the pyruvate kinase / lactate dehydrogenase protocol in A25A buffer (25 mM ACES potassium pH 6.9, 2 mM magnesium-acetate, 2 mM potassium-EGTA, 0.1 mM potassium-EDTA, 1 mM - mercaptoethanol).
- IC 50 values for the in vitro inhibition of ATPase activity of motor kinesin proteins are determined according to the method described in DeBonis, S. et al (2003) Biochemistry 42, 338-349. Monastrol has been used as a positive control. When necessary, the inhibitor concentrations were adjusted according to the initial IC50. Each inhibitor concentration was measured one to three times and averaged data are reported with the margins of error ⁇ the standard deviation.
- HeLa cells were cultured on Dulbecco's Modified Eagle Medium (GIBCO, BRL) supplemented with 10% fetal bovine serum (Hyclone) and maintained in a humid incubator at 37 ° C under 5%. CO 2 .
- the cells were allowed to adhere for at least 36 h on poly-D-lysine coated glass in 24-well plates before adding the test compounds. After incubation with the test compounds for 8 h, the cells were fixed with 1% paraformaldehyde-PBS at 37 ° C. for 3 min, followed by incubation in 100% methanol at -20 ° C. for 5 min and washed. with PBS for 5 min.
- Purification of human Eg5 Purification of human Eg5 (monomeric construct Eg52-386) has already been described (DeBonis, S., et al., (2003).) Interaction of the mitotic inhibitor monastrol with human kinesin Eg5. Biochemistry 42, 338-349).
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Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008501362A JP2008534449A (ja) | 2005-03-15 | 2006-03-14 | 新しいジヒドロピリミジン誘導体およびそれらの抗癌剤としての使用 |
US11/908,710 US20080145453A1 (en) | 2005-03-15 | 2006-03-14 | Novel Dihydropyrimidine Derivatives And Their Use As Anti-Cancer Agents |
CA002601425A CA2601425A1 (fr) | 2005-03-15 | 2006-03-14 | Nouveaux derives dihydropyrimidines et leur utilisation comme agents anti-cancereux |
EP06726083A EP1885368A2 (fr) | 2005-03-15 | 2006-03-14 | Nouveaux derives dihydropyrimidines et leur utilisation comme agents anti-cancereux |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0502518 | 2005-03-15 | ||
FR0502518A FR2883284A1 (fr) | 2005-03-15 | 2005-03-15 | Nouveaux derives dihydropyrimidines et leur utilisation comme agents anti-cancereux |
Publications (3)
Publication Number | Publication Date |
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WO2006097617A2 true WO2006097617A2 (fr) | 2006-09-21 |
WO2006097617A3 WO2006097617A3 (fr) | 2006-12-28 |
WO2006097617B1 WO2006097617B1 (fr) | 2007-02-22 |
Family
ID=35169846
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/FR2006/000556 WO2006097617A2 (fr) | 2005-03-15 | 2006-03-14 | Nouveaux derives dihydropyrimidines et leur utilisation comme agents anti-cancereux |
Country Status (6)
Country | Link |
---|---|
US (1) | US20080145453A1 (fr) |
EP (1) | EP1885368A2 (fr) |
JP (1) | JP2008534449A (fr) |
CA (1) | CA2601425A1 (fr) |
FR (1) | FR2883284A1 (fr) |
WO (1) | WO2006097617A2 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8741915B2 (en) | 2009-09-25 | 2014-06-03 | N30 Pharmaceuticals, Inc. | Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors |
US8906933B2 (en) | 2010-09-24 | 2014-12-09 | N30 Pharmaceuticals, Inc. | Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8318663B2 (en) | 2008-11-26 | 2012-11-27 | Satiogen Pharmaceuticals, Inc. | Methods of treating diabetes and/or obesity using an enteroendocrine peptide secretion enhancing agent |
CN102316872B (zh) | 2008-11-26 | 2016-12-21 | 萨蒂奥根制药公司 | 治疗肥胖症和糖尿病的胆汁酸再循环抑制剂 |
ES2552657T3 (es) | 2010-05-26 | 2015-12-01 | Satiogen Pharmaceuticals, Inc. | Inhibidores del reciclado de ácidos biliares y saciógenos para el tratamiento de diabetes, obesidad, y afecciones gastrointestinales inflamatorias |
PL2771003T3 (pl) | 2011-10-28 | 2017-10-31 | Lumena Pharmaceuticals Llc | Inhibitory ponownego wykorzystania kwasów żółciowych do leczenia pediatrycznych cholestatycznych chorób wątroby |
EP2682389A1 (fr) * | 2012-07-02 | 2014-01-08 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Dihydropyrimidine-2(1h)-ones et dihydropyrimidin-2(1h)-thiones en tant qu'inhibiteurs de symport d'iodure de sodium |
WO2016004028A1 (fr) * | 2014-07-01 | 2016-01-07 | Latif Rauf | Dérivés 2-oxopyrimidine-5-carboxylate pour le traitement de maladies de la thyroïde |
US10052326B1 (en) | 2017-10-12 | 2018-08-21 | King Saud University | Antihepatotoxic agents |
US10047071B1 (en) | 2018-01-15 | 2018-08-14 | King Saud University | Dihydropyrimidinone derivatives |
CN111358792A (zh) * | 2020-03-13 | 2020-07-03 | 中国人民解放军第四军医大学 | Kif11抑制剂monastrol抑制病理性疼痛的应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997042956A1 (fr) * | 1996-05-16 | 1997-11-20 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines et leurs emplois |
WO2002066443A2 (fr) * | 2001-02-21 | 2002-08-29 | Ono Pharmaceutical Co., Ltd. | Derives de 2-thioxo-1,2,3,4-tetrahydropyrimidine |
WO2002079169A1 (fr) * | 2001-03-29 | 2002-10-10 | Bristol-Myers Squibb Company | Composes de dihydropyrimidine cyano-substitues et leur utilisation pour traiter des maladies |
Family Cites Families (1)
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WO2003052106A1 (fr) * | 2001-12-17 | 2003-06-26 | Children's Medical Center Corporation | Procede de criblage de composes |
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2005
- 2005-03-15 FR FR0502518A patent/FR2883284A1/fr not_active Withdrawn
-
2006
- 2006-03-14 WO PCT/FR2006/000556 patent/WO2006097617A2/fr active Application Filing
- 2006-03-14 JP JP2008501362A patent/JP2008534449A/ja not_active Withdrawn
- 2006-03-14 CA CA002601425A patent/CA2601425A1/fr not_active Abandoned
- 2006-03-14 US US11/908,710 patent/US20080145453A1/en not_active Abandoned
- 2006-03-14 EP EP06726083A patent/EP1885368A2/fr not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997042956A1 (fr) * | 1996-05-16 | 1997-11-20 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines et leurs emplois |
WO2002066443A2 (fr) * | 2001-02-21 | 2002-08-29 | Ono Pharmaceutical Co., Ltd. | Derives de 2-thioxo-1,2,3,4-tetrahydropyrimidine |
WO2002079169A1 (fr) * | 2001-03-29 | 2002-10-10 | Bristol-Myers Squibb Company | Composes de dihydropyrimidine cyano-substitues et leur utilisation pour traiter des maladies |
Non-Patent Citations (10)
Title |
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BRINDABAN C. RANU ET ALL.: "Indium (III) Chloride-Catalysed One-Pot Synthesis of Dihydropyrimidinones by a Three-Component Coupling of 1,3-Dicarbonyl Compounds, Aldehydes, and Urea: An Improved Procedure for the Biginelli Reaction" J.ORG.CHEM., vol. 65, no. 19, 2000, pages 6270-6272, XP002403821 * |
DATABASE BEILSTEIN BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002354728 Database accession no. BRN: 9919278; 9919872; 5814739;9919278;8988325; & ZHU, YULIN; PAN, YUANJIANG; HUANG, SHENLIN: SYNTH. COMMUN., vol. 34, no. 17, 2004, pages 3167-3174, * |
DATABASE CA [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; LI, MING ET AL: "One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by nontoxic ionic liquid" XP002403834 extrait de STN Database accession no. 2005:1000235 & YOUJI HUAXUE , 25(9), 1062-1065 CODEN: YCHHDX; ISSN: 0253-2786, 2005, * |
DATABASE CA [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; MOBINIKHALEDI, A. ET AL: "Synthesis of some thioxopyrimidines, thiazolopyrimidines, thiazolodipyrimidines and pyrazolothiazolopyrimidines" XP002403833 extrait de STN Database accession no. 2005:484838 & PHOSPHORUS, SULFUR AND SILICON AND THE RELATED ELEMENTS , 180(7), 1713-1719 CODEN: PSSLEC; ISSN: 1042-6507, 2005, * |
DATABASE CHEMCATS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002403829 & "Screening Collection" 11 août 2003 (2003-08-11), "ZELINSKY INSTITUTE OF ORGANIC CHEMISTRY", 47 LENINSKY PROSPECT, MOSCOW, 117913, RUSSIA * |
DATABASE CHEMCATS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002403830 & "Chemdiv, Inc. Product Libary" 25 avril 2003 (2003-04-25), CHEMDIV, INC. 11558 SORRENTO VALLEY ROAD SUITE 5 SAN DIEGO, CA, 92121 USA * |
DATABASE CHEMCATS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002403831 & "Interchim Intermediates" 18 janvier 2005 (2005-01-18), INTERCHIM 211 BIS AV. J.F.KENNEDY BP 1140, MONTLUCON, 03103, FRANCE * |
DATABASE CHEMCATS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002403832 & "Chembridge Sceening Library" 12 janvier 2005 (2005-01-12), CHEMBRIDGE CORPORATION, 16981 VIA TAZON, SUITE G, SAN DIEGO, CA, 92127, USA * |
KAPPE C O ET AL: "X-Ray Structure, Conformational Analysis, Enantioseparation, and Determination of Absolute Configuration of the Mitotic Kinesin Eg5 Inhibitor Monastrol" TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 56, no. 13, mars 2000 (2000-03), pages 1859-1862, XP004192632 ISSN: 0040-4020 * |
KAPPE C O: "Biologically active dihydropyrimidones of the Biginelli-type - a literature survey" EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 35, no. 12, décembre 2000 (2000-12), pages 1043-1052, XP004372823 ISSN: 0223-5234 * |
Cited By (4)
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US8741915B2 (en) | 2009-09-25 | 2014-06-03 | N30 Pharmaceuticals, Inc. | Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors |
US9067893B2 (en) | 2009-09-25 | 2015-06-30 | Nivalis Therapeutics, Inc. | Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors |
US9283229B2 (en) | 2009-09-25 | 2016-03-15 | Nivalis Therapeutics, Inc. | Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors |
US8906933B2 (en) | 2010-09-24 | 2014-12-09 | N30 Pharmaceuticals, Inc. | Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists |
Also Published As
Publication number | Publication date |
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US20080145453A1 (en) | 2008-06-19 |
WO2006097617A3 (fr) | 2006-12-28 |
JP2008534449A (ja) | 2008-08-28 |
FR2883284A1 (fr) | 2006-09-22 |
WO2006097617B1 (fr) | 2007-02-22 |
EP1885368A2 (fr) | 2008-02-13 |
CA2601425A1 (fr) | 2006-09-21 |
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