Claims
- 1. A compound of the formula:
- 2. The compound of claim 1, wherein each R1-R3 is independently halo, NO, NO2, CN, SO2H, SO3H, optionally substituted alkyl (1-12C), alkenyl (2-12C), alkynyl (2-12C), aryl (6-12C) or arylalkyl, arylalkenyl or arylalkynyl (each 7-16C) wherein in each of the foregoing 1-4C may be replaced by a heteroatom (Si, N, O and/or S) and wherein said optional substituents may include ═O and wherein when alkyl, alkenyl, or alkynyl comprises at least one cyclic moiety, the number of C contained may be up to and including 18, wherein one or more C may be replaced by a heteroatom, and
wherein two substituents at adjacent positions on the same ring may form a 3-7 membered saturated or unsaturated ring fused to said substituted ring, said fused ring is optionally itself substituted and optionally contains one or more heteroatoms (N, S, O), and wherein R1 may be keto.
- 3. The compound of claim 1, wherein X is alkyl (1-12C) or alkenyl (2-12C) optionally including one or more N, O or S with the proviso that any N included in a ring is secondary or is tertiary solely because of an alkyl substitution.
- 4. The compound of claim 3, wherein X is acyclic.
- 5. The compound of claim 1, wherein X is aryl, provided that if aryl is phenyl or pyridyl, said aryl must contain at least one substituent and wherein if said aryl is phenyl and contains only one substituent, said substituent must comprise an aryl group or a trialkylsilyl group and wherein said phenyl is not 2,3-dimethylphenyl or fused to an aliphatic ring.
- 6. The compound of claim 5, wherein X is benzimidazole, benzothiazole, or substituted phenyl.
- 7. The compound of claim 1, wherein CRH-aryl wherein R is H, alkyl, or a heteroaromatic ring, wherein when R is H, aryl is optionally substituted 4-pyridyl, or is substituted phenyl other than phenyl fused to an aliphatic ring, or is substituted naphthyl or is substituted 5-membered aryl.
- 8. The compound of claim 7, wherein R is cyclopropyl or a thiophene residue.
- 9. The compound of claim 1, wherein X is alkylene-aryl wherein said alkylene contains at least 2 C, and further optionally contains one heteroatom and/or is substituted by ═O and/or OH provided that if said alkylene is CH2CH2, CH2CH2CH2, CH2CH2O or CH2CH2CH2O, and said aryl is phenyl, said phenyl must be substituted; and if said alkylene is CH2CH2CH2O substituted by OH, said aryl is other than substituted quinolyl or monosubstituted phenyl.
- 10. The compound of claim 9, wherein said alkylene comprises a keto substituent.
- 11. The compound of claim 9, wherein X is substituted phenyl coupled to (CH2)n— or Y(CH2)n, wherein n is 2-5, and Y is NH, O or S.
- 12. The compound of claim 1, wherein at least one of n1-n3 is 0.
- 13. The compound of claim 1, wherein n1 is 0 or R1 is alkyl
- 14. The compound of claim 1, wherein both n2 and n3 are 0.
- 15. The compound of claim 1, wherein all of n1-n3 are 0.
- 16. The compound of claim 1 which is
1-{4-[4-(4-Fluoro-benzyl)-phenyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; 1-[4-(3,5-Di-tert-butyl-4-hydroxy-benzyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 1-{4-[3-(4-Amino-2,3,5-trimethyl-phenoxy)-2-hydroxy-propyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; 1-(4-Adamantan-1-ylmethyl-piperazin-1-yl)-3,3-diphenyl-propan-1-one; 1-(4-Benzothiazol-2-yl-piperazin-1-yl)-3,3-diphenyl-propan-1-one; 3,3-Diphenyl-1-{4-[2-(3,4,5-trimethoxy-phenoxy)-ethyl]-piperazin-1-yl}-propan-1-one; 1-{4-[2-(3,4-Dimethoxy-phenoxy)-ethyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; 1-{4-[2-(Benzothiazol-2-ylsulfanyl)-ethyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; N-(2,6-Dimethyl-phenyl)-2-[4-(3,3-diphenyl-propionyl)-piperazin-1-yl]-acetamide; 2-[4-(3,3-Diphenyl-propionyl)-piperazin-1-yl]-N-methyl-N-phenyl-acetamide; 3,3-Diphenyl-1-[4-(1-phenyl-ethyl)-piperazin-1-yl]-propan-1-one; 1-[4-(2-Diallylamino-ethyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 1-[4-(2-Dipropylamino-ethyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 1-(4-sec-Butyl-piperazin-1-yl)-3,3-diphenyl-propan-1-one; 1-[4-(1-Ethyl-propyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 1-[4-(1-Methyl-piperidin-3-ylmethyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 1-(4-Heptyl-piperazin-1-yl)-3,3-diphenyl-propan-1-one; 3,3-Diphenyl-1-(4-pyridin-4-ylmethyl-piperazin-1-yl)-propan-1-one; 1-[4-(3,5-Dichloro-phenyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 1-(4-Cycloheptyl-piperazin-1-yl)-3,3-diphenyl-propan-1-one; 1-[4-(3,4-Dimethyl-phenyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 1-(4-Biphenyl-4-yl-piperazin-1-yl)-3,3-diphenyl-propan-1-one; 1-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 1-[4-(1-Methyl-piperidin-4-ylmethyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; N-{2-[4-(3,3-Diphenyl-propionyl)-piperazin-1-yl]-ethyl}-3,4,5-trimethoxy-benzamide; 1-(4-Isopropyl-piperazin-1-yl)-3,3-diphenyl-propan-1-one; 1-[4-(3-Dimethylamino-propyl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 3,3-Diphenyl-1-[4-(4-trimethylsilanyl-phenyl)-piperazin-1-yl]-propan-1-one; 3,3-Diphenyl-1-[4-(2-phenylamino-ethyl)-piperazin-1-yl]-propan-1-one; 1-{4-[2-(2,4-Difluoro-phenoxy)-ethyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; 3,3-Diphenyl-1-{4-[2-(2,3,5,6-tetrafluoro-phenoxy)-ethyl]-piperazin-1-yl}-propan-1-one; 1-[4-(1-Benzyl-1H-benzoimidazol-2-yl)-piperazin-1-yl]-3,3-diphenyl-propan-1-one; 3,3-Diphenyl-1-[4-(phenyl-thiophen-2-yl-methyl)-piperazin-1-yl]-propan-1-one; 1-{4-[Cyclopropyl-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; (4-{2-[4-(3,3-Diphenyl-propionyl)-piperazin-1-yl]-ethoxy}-2,3,6-trimethyl-phenyl)-carbamic acid tert-butyl ester; 1-{4-[2-(4-Amino-2,3,5-trimethyl-phenoxy)-ethyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; 1-{4-[2-(4-Methoxy-phenoxy)-ethyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; 1-{4-[2-(Benzo[1,3]dioxol-5-yloxy)-ethyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; 1-{4-[2-(2,4-Dichloro-phenoxy)-ethyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; 1-{4-[2-(4-Fluoro-phenoxy)-ethyl]-piperazin-1-yl}-3,3-diphenyl-propan-1-one; or 3,3-Diphenyl-1-[4-(2-phenylsulfanyl-ethyl)-piperazin-1-yl]-propan-1-one; or a salt thereof.
- 17. A pharmaceutical composition for use in treating conditions characterized by abnormal calcium channel activity which composition comprises, in admixture with a pharmaceutically acceptable excipient, a dosage amount of at least one compound of claim 1.
- 18. A method to treat conditions associated with abnormal 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. 10/060,900 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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Number |
Date |
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Parent |
09476927 |
Dec 1999 |
US |
Child |
10060900 |
Jan 2002 |
US |
Continuation in Parts (3)
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Number |
Date |
Country |
Parent |
10060900 |
Jan 2002 |
US |
Child |
10655393 |
Sep 2003 |
US |
Parent |
09401699 |
Sep 1999 |
US |
Child |
09476927 |
Dec 1999 |
US |
Parent |
09107037 |
Jun 1998 |
US |
Child |
09401699 |
Sep 1999 |
US |