التفاصيل البيبلوغرافية
| العنوان: |
Compounds Useful In Therapy |
| Document Number: |
20080096950 |
| تاريخ النشر: |
April 24, 2008 |
| Appl. No: |
11/866565 |
| Application Filed: |
October 03, 2007 |
| مستخلص: |
Compounds of Formula (I): [chemical expression included] and pharmaceutically acceptable salts, solvates (including hydrates) of said compounds and salts, or prodrugs of said compound, or pharmaceutically acceptable salts or solvates of said prodrugs, wherein the substituents are as herein defined, are useful in therapy, for example they may be useful for treating progesterone-mediated conditions such as endometriosis, uterine fibroids (leiomyomata), menorrhagia, adenomyosis, primary and secondary dysmenorrhoea (including symptoms of dyspareunia, dyschexia and chronic pelvic pain), or chronic pelvic pain syndrome. |
| Inventors: |
Gibson, Karl Richard (Sandwich, GB); Skerratt, Sarah Elizabeth (Sandwich, GB); Dack, Kevin Neil (Sandwich, GB) |
| Claim: |
1. A compound of Formula (I) [chemical expression included] or a pharmaceutically acceptable salt, solvate (including hydrate) of said compounds and salt, or a prodrug of said compound, or a pharmaceutically acceptable salt or solvate of said prodrug, wherein: R1 and R2 are independently selected from H, C1-6 alkyl optionally substituted by one or more halogen, C1-6alkyloxy optionally substituted by one or more halogen, CN, and halo; R3 is selected from the group consisting of H; C1-6alkyl; C1-6alkyloxy; C3-8cycloalkyl; and halo; R4 is C1-6 alkyl optionally substituted by one or more fluorine and/or nitrile groups, C1-6alkyloxy, C3-8cycloalkyl optionally substituted by one or more fluorine and/or nitrile groups, or halo; X represents O, S, S(O) or SO2; Z represents a bond or (CR5R6); where R5 and R6 are independently selected from the group consisting of H and C1-6alkyl; or R5 and R6, together with the carbon to which they are attached, form a 3 to 6 membered carbocyclic ring which optionally bears from 1 to 3 substituents independently selected from the group consisting of halo; cyano; hydroxyl; C1-4alkyl; C1-4haloalkyl; C1-4haloalkyloxy and C1-4alkyloxy; and m and n independently are 0, 1 or 2 provided that m+n is not more than 3; and wherein said alkyl, cycloalkyl or alkoxy groups are independently optionally substituted with from 1 to 5 substituents independently selected from the group consisting of halo, cyano, hydroxyl, C1-4alkyl; C1-4haloalkyl; C1-4haloalkyloxy and C1-4alkyloxy. |
| Claim: |
2. A compound, salt, solvate or prodrug according to claim 1 wherein R1 and R2 are independently H, Cl, C1-3 alkyl, optionally substituted by one or more halogen, or C1-3 alkyloxy, optionally substituted by one or more halogen. |
| Claim: |
3. A compound, salt, solvate or prodrug according to claim 1 wherein R3 is methyl, ethyl, cyclopropyl, or chloro. |
| Claim: |
4. A compound, salt, solvate or prodrug according to claim 1 wherein R4 is C1-6 alkyl or C3-8 cycloalkyl. |
| Claim: |
5. A compound, salt, solvate or prodrug according to claim 1 wherein Z is a bond or (CH2). |
| Claim: |
6. A compound, salt, solvate or prodrug according to claim 1 wherein m+n is zero, or m is 1 and n is 1. |
| Claim: |
7. A compound, salt, solvate or prodrug according to claim 1 wherein R1 and R2 are independently H, Cl, CH3, CF3, OCF3 or OCH3. |
| Claim: |
8. A compound, salt, solvate or prodrug according to claim 1 wherein R3 is methyl or cyclopropyl. |
| Claim: |
9. A compound, salt, solvate or prodrug according to claim 1 wherein R4 is C1-4 alkyl or C3-4 cycloalkyl. |
| Claim: |
10. A compound, salt, solvate or prodrug according to claim 1 wherein Z is a bond. |
| Claim: |
11. A compound, salt, solvate or prodrug according to claim 1 wherein X is O or SO2. |
| Claim: |
12. A compound, salt, solvate or prodrug according to claim 1 wherein R1 or R2 is CH3. |
| Claim: |
13. A compound, salt, solvate or prodrug according to claim 1 wherein R4 is methyl, isopropyl, cyclopropyl or cyclobutyl. |
| Claim: |
14. A compound, salt, solvate or prodrug according to claim 13 wherein R4 is cyclopropyl. |
| Claim: |
15. A compound, salt, solvate or prodrug according to claim 1 wherein X is SO2. |
| Claim: |
16. A compound according to claim 1 selected from the group consisting of: 4-(3,5-dicyclopropyl-1-oxetan-3-yl-1H-pyrazol-4-yloxy)-2,6-dimethyl-benzonitrile; 4-[3,5-dicyclopropyl-1-(1,1-dioxo-thietan-3-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[3,5-dicyclopropyl-1-(tetrahydro-furan-3-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[3,5-dicyclopropyl-1-(tetrahydro-thiopyran-4-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[3,5-dicyclopropyl-1-(1,1-dioxo-hexahydro-1 λ6-th iopyran-4-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[3,5-dicyclopropyl-1-(tetrahydro-pyran-4-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[3,5-dicyclopropyl-1-(1,1-dioxo-tetrahydro-1λ6-thiophen-3-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-(3-cyclopropyl-5-methyl-1-(1,1-dioxo-thietan-3-yl)-1H-pyrazol-4-yloxy)-2,6-dimethyl-benzonitrile; 4-(3-methyl-5-cyclopropyl-1-(1,1-dioxo-thietan-3-yl)-1H-pyrazol-4-yloxy)-2,6-dimethyl-benzonitrile; 4-[5-cyclobutyl-1-(1,1-dioxo-tetrahydro-1λ6-thiophen-3-yl)-3-methyl-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[3-cyclobutyl-1-(1,1-dioxo-tetrahydro-1λ6-thiophen-3-yl)-5-methyl-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[5-cyclopropyl-1-(1,1-dioxo-tetrahydro-1λ6-thiophen-3-yl)-3-methyl-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[3-cyclopropyl-1-(1,1-dioxo-tetrahydro-1λ6-thiophen-3-yl)-5-methyl-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-(3-cyclopropyl-5-methyl-1-(1,1-dioxo-1λ6-thietan-3-yl)-1H-pyrazol-4-yloxy)-2-methyl-benzonitrile; 4-(3-cyclopropyl-5-methyl-1-(1,1-dioxo-1λ6-thietan-3-yl)-1H-pyrazol-4-yloxy)-2-chloro-benzonitrile; 4-[5-cyclopropyl-1-(1,1-dioxo-1λ6-thietan-3-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[3-cyclopropyl-1-(1,1-dioxo-1λ6-thietan-3-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; 4-[5-chloro-3-cyclopropyl-1-(1,1-dioxo-1λ6-thietan-3-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; and 4-[3-chloro-5-cyclopropyl-1-(1,1-dioxo-1λ6-thietan-3-yl)-1H-pyrazol-4-yloxy]-2,6-dimethyl-benzonitrile; or a salt, solvate, racemate, enantiomer, or prodrug thereof. |
| Claim: |
17. A pharmaceutical formulation comprising a compound, salt, solvate or prodrug according to claim 1 together with a pharmaceutically acceptable excipient, diluent or carrier. |
| Claim: |
18. A method of treatment of a mammal to treat endometriosis, uterine fibroids, menorrhagia, adenomyosis, primary and secondary dysmenorrhoea, or chronic pelvic pain syndrome comprising treating said mammal with an effective amount of a compound, salt, solvate or prodrug according to claim 1 or a composition thereof. |
| Claim: |
19. A method according to claim 18, wherein the disease or disorder is endometriosis or uterine fibroids. |
| Current U.S. Class: |
514/407 |
| Current International Class: |
61; 61; 07 |
| رقم الانضمام: |
edspap.20080096950 |
| قاعدة البيانات: |
USPTO Patent Applications |