CA2371642A1 - Derives d'uree et d'amide cycliques - Google Patents
Derives d'uree et d'amide cycliques Download PDFInfo
- Publication number
- CA2371642A1 CA2371642A1 CA002371642A CA2371642A CA2371642A1 CA 2371642 A1 CA2371642 A1 CA 2371642A1 CA 002371642 A CA002371642 A CA 002371642A CA 2371642 A CA2371642 A CA 2371642A CA 2371642 A1 CA2371642 A1 CA 2371642A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- alkyl
- aryl
- heterocyclic
- alkoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000003950 cyclic amides Chemical class 0.000 title description 3
- ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical class OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 126
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 61
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- 125000003118 aryl group Chemical group 0.000 claims abstract description 50
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 48
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 37
- 125000001424 substituent group Chemical group 0.000 claims abstract description 36
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 25
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- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 21
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 15
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- 239000000126 substance Substances 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims abstract 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 62
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- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
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- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 2
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 26
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- 239000000186 progesterone Substances 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
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- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 13
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- 238000003556 assay Methods 0.000 description 13
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- 238000012360 testing method Methods 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
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- 239000003153 chemical reaction reagent Substances 0.000 description 11
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- 239000000583 progesterone congener Substances 0.000 description 11
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000005089 Luciferase Substances 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
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- 239000001963 growth medium Substances 0.000 description 9
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
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- 125000004432 carbon atom Chemical group C* 0.000 description 8
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- 238000004458 analytical method Methods 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 5
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- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 229950011093 onapristone Drugs 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 238000000424 optical density measurement Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000001408 paramagnetic relaxation enhancement Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 1
- 239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002379 progesterone receptor modulator Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229940095745 sex hormone and modulator of the genital system progesterone receptor modulator Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 210000002325 somatostatin-secreting cell Anatomy 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
L'invention concerne des composés de formule I. Dans ladite formule, A, B et D sont N ou CH, à condition que A, B et D ne puissent pas tous être CH; R?1¿ et R?2¿ sont des substituants indépendants qui peuvent être H, COR?A¿, NR?B¿COR?A¿, ou des groupes alkyle éventuellement substitué, alcényle, alkynyle, cycloalkyle ou aryle; ou bien R?1¿ et R?2¿ sont fusionnés pour former une chaîne alkyle spirocyclique éventuellement substituée comprenant de 3 à 8 éléments, alcényle ou hétérocyclique; R?A¿ est H ou alkyle éventuellement substitué, aryle, alcoxy, ou aminoalkyle; R?B¿ est H, alkyle C¿1-3?, ou alkyle C¿1-3? substitué; R?3¿ est H, OH, NH¿2?, ou alkyle éventuellement substitué, ou alcényle, ou COR?C¿; R?C¿ est H ou alkyle éventuellement substitué, aryle, alcoxy, ou aminoalkyle; R?4¿ est une chaîne benzène substituée ou une chaîne à 5 ou 6 éléments comportant 1, 2 ou 3 hétéroatomes pouvant être O, S, SO, SO¿2? ou NR?5¿; R?F¿ est H ou alkyle éventuellement substitué, aryle, alcoxy, ou aminoalkyle; R?G¿ est H, alkyle, ou alkyle substitué; R?5¿ est H ou alkyle; Q est O, S, NR?6¿, ou CR?7¿R?8¿; R?6¿ est CN, SO¿2?CF¿3?, ou une chaîne alkyle éventuellement substituée, cycloalkyle, aryle, ou hétérocyclique; R?7¿ et R?8¿ sont H, NO¿2?, CN CO¿2?R?9¿, ou une chaîne alkyle éventuellement substituée, cycloalkyle, aryle, ou hétérocyclique; R?9¿ est alkyle C¿1-3?; ou CR?7¿R?8¿ forme une chaîne à 6 éléments dont la structure est représentée ci-dessous. W est O ou une liaison chimique. Il peut s'agir d'un sel pharmaceutiquement acceptable des dérivés considérés. L'invention concerne en outre l'utilisation de ces dérivés, et des compositions pharmaceutiques tenant lieu d'agonistes et d'antagonistes vis-à-vis du récepteur de progestérone.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18303799P | 1999-05-04 | 1999-05-04 | |
| US60/183,037 | 1999-05-04 | ||
| US09/552,356 US6369056B1 (en) | 1999-05-04 | 2000-04-19 | Cyclic urea and cyclic amide derivatives |
| US09/552,356 | 2000-04-19 | ||
| PCT/US2000/011836 WO2000066592A1 (fr) | 1999-05-04 | 2000-05-01 | Derives d'uree et d'amide cycliques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2371642A1 true CA2371642A1 (fr) | 2000-11-09 |
Family
ID=56290016
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002371642A Abandoned CA2371642A1 (fr) | 1999-05-04 | 2000-05-01 | Derives d'uree et d'amide cycliques |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1173443A1 (fr) |
| JP (1) | JP2002543206A (fr) |
| AU (1) | AU4689600A (fr) |
| CA (1) | CA2371642A1 (fr) |
| MX (1) | MXPA01011291A (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060122262A1 (en) | 2002-10-29 | 2006-06-08 | Lephart Edwin D | Use of equol for treating androgen mediated diseases |
-
2000
- 2000-05-01 AU AU46896/00A patent/AU4689600A/en not_active Abandoned
- 2000-05-01 EP EP00928699A patent/EP1173443A1/fr not_active Withdrawn
- 2000-05-01 MX MXPA01011291A patent/MXPA01011291A/es unknown
- 2000-05-01 CA CA002371642A patent/CA2371642A1/fr not_active Abandoned
- 2000-05-01 JP JP2000615622A patent/JP2002543206A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU4689600A (en) | 2000-11-17 |
| JP2002543206A (ja) | 2002-12-17 |
| EP1173443A1 (fr) | 2002-01-23 |
| MXPA01011291A (es) | 2003-07-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |