Claims
- 1. A compound of the formula:
- 2. The compound of claim 1 which is of the formula
- 3. The compound of claim 1 which is of the formula
- 4. The compound of claim 1 which is of the formula
- 5. The compound of claim 1, wherein each non-interfering substituent is independently alkyl (1-10C), alkenyl (2-10C), alkynyl (2-10C), aryl (6-10C), arylalkyl (7-16C) or arylalkenyl (7-16C) each optionally further containing 1-4 heteroatoms (N, O or S) each further optionally substituted, or is independently ═O, halo, CF3, OCF, NO2, NH2, OH, or SH wherein S may optionally be oxidized.
- 6. The compound of claim 1, wherein the phenyl groups represented by A and B are linked through a bond, one or more CR2 moieties wherein each R is H or lower alkyl (1-6C) wherein one or more of said CR2 may be replaced by NR, O or S.
- 7. The compound of claim 1, wherein each 1 is independently 0 or 1.
- 8. The compound of claim 1, wherein X2 is substituted by ═O adjacent the piperazine ring.
- 9. The compound of claim 1, wherein X1 is substituted by ═O at the position next to the piperazine ring.
- 10. The compound of claim 1, wherein each of R2 and R3 is independently alkoxy, halo, or alkyl.
- 11. The compound of claim 1, wherein m is 1 and R1 is ═O or a carboxylic acid group or ester or amide thereof.
- 12. The compound of claim 1, wherein Ar is optionally substituted phenyl.
- 13. The compound of claim 12, wherein said phenyl is unsubstituted or is substituted by one or more tert-butyl, methoxy, substituted alkoxy, hydroxy and/or halo.
- 14. The compound of claim 13, wherein the substituted alkoxy is substituted by an amino group.
- 15. The compound of claim 1, wherein Ar is optionally substituted pyrimidyl, pyridyl, benzothiazole, benzimidazole or indole.
- 16. The compound of claim 1, which is
6,6-Bis-(4-fluoro-phenyl)-1-[4-(2-phenylsulfanyl-ethyl)-piperazin-1-yl]-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-[2-(4-fluoro-phenoxy)-ethyl]-piperazine; 1-{4-[2-(Benzo[1,3]dioxol-5-yloxy)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(2-phenylsulfanyl-ethyl)-piperazine; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-[2-(4-methoxy-phenoxy)-ethyl]-piperazine; 1-{4-[2-(2,4-Difluoro-phenoxy)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 6,6-Bis-(4-fluoro-phenyl)-1-[4-(2-phenoxy-ethyl)-piperazin-1-yl]-hexan-1-one; 1-{4-[2-(2,4-Dichloro-phenoxy)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 6,6-Bis-(4-fluoro-phenyl)-1-{4-[2-(4-methoxy-phenoxy)-ethyl]-piperazin-1-yl}-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(2-phenoxy-ethyl)-piperazine; 6,6-Bis-(4-fluoro-phenyl)-1-{4-[2-(3,4,5-trimethoxy-phenoxy)-ethyl]-piperazin-1-yl}-hexan-1-one; 1-{4-[2-(Benzothiazol-2-ylsulfanyl)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; [4-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-piperazin-1-yl}-ethoxy)-2,3,6-trimethyl-phenyl]-carbamic acid tert-butyl ester; 4-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-ethoxy)-2,3,6-trimethyl-phenylamine; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-[2-(2,4-dichloro-phenoxy)-ethyl]-piperazine; [2-(4-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-ylmethyl}-2,6-di-tert-butyl-phenoxy)-ethyl]-dimethyl-amine; 4-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-ylmethyl}-2,6-di-tert-butyl-phenol; 1-[4-(3,5-Di-tert-butyl-4-methoxy-benzoyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[4-(3,5-Di-tert-butyl-4-methoxy-benzyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,5-di-tert-butyl-4-methoxy-benzyl)-piperazine; {4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-(3,5-di-tert-butyl-4-methoxy-phenyl)-methanone; 1-{4-[3,5-Di-tert-butyl-4-(2-dimethylamino-ethoxy)-benzoyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-Benzo[1,3]dioxol-5-ylmethyl-4-[6,6-bis-(4-fluoro-phenyl)-hexyl]-piperazine; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,5-di-tert-butyl-benzyl)-piperazine; {4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-(3,5-di-tert-butyl-4-hydroxy-phenyl)-methanone; 1-[4-(3,5-Di-tert-butyl-4-hydroxy-benzyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[4-(3,5-Dibromo-4-hydroxy-benzoyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[4-(3,5-Di-tert-butyl-4-hydroxy-benzoyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[4-(3,5-Di-tert-butyl-benzoyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(4-tert-butyl-benzyl)-piperazine; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(9H-thioxanthen-9-yl)-piperazine; 2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-benzothiazole; 6,6-Bis-(4-fluoro-phenyl)-1-(4-pyrimidin-2-yl-piperazin-1-yl)-hexan-1-one; 2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-pyrimidine; 6,6-Bis-(4-fluoro-phenyl)-1-[4-(9H-thioxanthen-9-yl)-piperazin-1-yl]-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,4,5-trimethoxy-benzyl)-piperazine-2-carboxylic acid ethyl ester; 6,6-Bis-(4-fluoro-phenyl)-1-{4-[2-(3,4,5-trimethoxy-benzylamino)-ethyl]-piperazin-1-yl}-hexan-1-one; 9,9-Bis-(4-fluoro-phenyl)-1-[4-(3,4,5-trimethoxy-benzyl)-piperazin-1-yl]-nonan-1-one; (2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-ethyl)-phenyl-amine; 1-[9,9-Bis-(4-fluoro-phenyl)-nonyl]-4-(3,4,5-trimethoxy-benzyl)-piperazine; (4-{4-[Bis-(4-fluoro-phenyl)-methoxy]-butyl}-piperazin-1-yl)-(3,4,5-trimethoxy-phenyl)-methanone; 6,6-Bis-(4-fluoro-phenyl)-1-[4-(4-trifluoromethoxy-benzoyl)-piperazin-1-yl]-hexan-2-one; 1-[4-(4-Bromo-benzoyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 6,6-Bis-(4-fluoro-phenyl)-5-hydroxy-1-[4-(3,4,5-trimethoxy-benzoyl)-piperazin-1-yl]-hexan-1-one; 1-{4-[Bis-(4-fluoro-phenyl)-methoxy]-butyl}-4-(3,4,5-trimethoxy-benzyl)-piperazine; 6,6-Bis-(4-fluoro-phenyl)-6-hydroxy-1-[4-(3,4,5-trimethoxy-benzoyl)-piperazin-1-yl]-hexan-1-one; 4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-1-(3,4,5-trimethoxy-benzyl)-piperazine-2-carboxylic acid; 4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-1-(3,4,5-trimethoxy-benzyl)-piperazin-2-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-4-(3,5-di-tert-butyl-4-methoxy-benzoyl)-piperazin-2-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,4,5-trimethoxy-benzoyl)-piperazin-2-one; 4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-1-(3,4,5-trimethoxy-benzyl)-piperazin-2-one; 4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-1-(3,5-di-tert-butyl-4-methoxy-benzyl)-piperazin-2-one; 4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-1-[2-(4-fluoro-phenoxy)-ethyl]-piperazin-2-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,5-di-tert-butyl-4-methoxy-benzoyl)-piperazin-2-one; 4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-1-(3,5-di-tert-butyl-4-methoxy-benzoyl)-piperazin-2-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,5-di-tert-butyl-4-methoxy-benzyl)-piperazin-2-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-4-(3,5-di-tert-butyl-4-hydroxy-benzoyl)-piperazin-2-one; 6,6-Bis-(4-fluoro-phenyl)-1-[4-(3,4,5-trimethoxy-benzoyl)-piperazin-1-yl]-hex-5-en-1-one; 1-{4-[2-(3,4-Dimethoxy-phenoxy)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-[2-(3,4-dimethoxy-phenoxy)-ethyl]-piperazine; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,4,5-trimethoxy-benzyl)-piperazine-2-carboxylic acid; 4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-1-(3,4,5-trimethoxy-benzyl)-piperazine-2-carboxylic acid ethyl ester; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,4-dimethoxy-benzyl)-piperazine; 1-[4-(3,4-Dimethoxy-benzoyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[2-(Benzo[1,3]dioxol-5-yloxy)-ethyl]-4-[6,6-bis-(4-fluoro-phenyl)-hexyl]-piperazine; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-[2-(3,4,5-trimethoxy-phenoxy)-ethyl]-piperazine; 1-(4-Amino-2,3,5-trimethyl-phenoxy)-3-{4-[6,6-bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-propan-2-ol; 1-{4-[3-(4-Amino-2,3,5-trimethyl-phenoxy)-2-hydroxy-propyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-(4-Benzothiazol-2-yl-piperazin-1-yl)-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(3,5-bis-trifluoromethyl-benzyl)-piperazine; 1-[4-(3,5-Bis-trifluoromethyl-benzoyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[4-(4-tert-Butyl-benzoyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(4-bromo-benzyl)-piperazine; 2-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-ethylsulfanyl)-benzothiazole; 6,6-Bis-(4-fluoro-phenyl)-1-[4-(4-hydroxy-3,5-dimethoxy-benzoyl)-piperazin-1-yl]-hexan-1-one; 4-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-ylmethyl}-2,6-dibromo-phenol; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-(4-trifluoromethoxy-benzyl)-piperazine; (2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-ethyl)-(3,4,5-trimethoxy-benzyl)-amine; 1-{4-[2-(4-Fluoro-phenoxy)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 6,6-Bis-(4-fluoro-phenyl)-1-[4-(2-phenylamino-ethyl)-piperazin-1-yl]-hexan-1-one; 1-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-4-[2-(2,4-difluoro-phenoxy)-ethyl]-piperazine; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-2-oxo-ethyl)-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-2-oxo-ethyl)-4-chloro-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-2-oxo-ethyl)-4-methyl-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-2-oxo-ethyl)-4-isopropyl-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-2-oxo-ethyl)-4-tert-butyl-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-yl}-2-oxo-ethyl)-4-fluoro-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-piperazin-1-yl}-2-oxo-ethyl)-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-piperazin-1-yl}-2-oxo-ethyl)-4-chloro-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-piperazin-1-yl}-2-oxo-ethyl)-4-methyl-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-piperazin-1-yl}-2-oxo-ethyl)-4-isopropyl-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-piperazin-1-yl}-2-oxo-ethyl)-4-tert-butyl-benzamide; N-(2-{4-[6,6-Bis-(4-fluoro-phenyl)-hexanoyl]-piperazin-1-yl}-2-oxo-ethyl)-4-fluoro-benzamide; 1-[4-(2-Benzylamino-ethyl)-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-{4-[2-(4-Chloro-benzylamino)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 6,6-Bis-(4-fluoro-phenyl)-1-{4-[2-(4-methyl-benzylamino)-ethyl]-piperazin-1-yl}-hexan-1-one; 6,6-Bis-(4-fluoro-phenyl)-1-{4-[2-(4-isopropyl-benzylamino)-ethyl]-piperazin-1-yl}-hexan-1-one; 1-{4-[2-(4-tert-Butyl-benzylamino)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-{4-[2-(4-Fluoro-benzylamino)-ethyl]-piperazin-1-yl}-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 6,6-Bis-(4-fluoro-phenyl)-1-[4-(1-hydroxy-pyridine-4-carbonyl)-piperazin-1-yl]-hexan-1-one; 4-{4-[6,6-Bis-(4-fluoro-phenyl)-hexyl]-piperazin-1-ylmethyl}-2,6-dimethoxy-phenol; 9,9-Diphenyl-1-[4-(3,4,5-trimethoxy-benzyl)-piperazin-1-yl]-nonan-1-one; 1-[4-(3,5-Di-tert-butyl-4-methoxy-benzoyl)-2-methyl-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[4-(3,5-Di-tert-butyl-4-methoxy-benzoyl)-3-methyl-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; 1-[4-(3,5-Di-tert-butyl-benzoyl)-2-methyl-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one; or 1-[4-(4-tert-Butyl-benzoyl)-2-methyl-piperazin-1-yl]-6,6-bis-(4-fluoro-phenyl)-hexan-1-one.
- 17. A pharmaceutical composition for use in treating conditions characterized by calcium channel activity which composition comprises, in admixture with a pharmaceutically acceptable excipient, a unit dosage amount of at least one compound of claim 1.
- 18. A method to treat conditions associated with calcium channel activity in a subject which method comprises administering to a subject in need of such treatment at least one compound of claim 1 or a pharmaceutical composition thereof.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No. 10/409,868 filed 8 Apr. 2003, which is a continuation-in-part of U.S. Ser. No. 10/060,900 filed 29 Jan. 2002, which is a continuation of U.S. Ser. No. 09/476,927 filed 30 Dec. 1999, now U.S. Pat. No. 6,387,897; which is a continuation-in-part of U.S. Ser. No. 09/401,699, filed 23 Sep. 1999, now U.S. Pat. No. 6,294,533; which is a continuation-in-part of U.S. Ser. No. 09/107,037 filed 30 Jun. 1998, now U.S. Pat. No. 6,011,035. The contents of these applications are incorporated herein by reference.
Continuations (1)
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09476927 |
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10060900 |
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Continuation in Parts (4)
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10409868 |
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10060900 |
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09401699 |
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09476927 |
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09107037 |
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09401699 |
Sep 1999 |
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