Abstract: Sequences and partial sequences for three types of mammalian (human and rat sequences identified) T-type calcium channel subunits which we have labeled as the ?1G, ?1H and ?1I subunits are provided. Knowledge of the sequence of these calcium channel permits the localization and recovery of the complete sequence from human cells, and the development of cell lines which express the novel calcium channels of the invention. These cells may be used for identifying compounds capable of acting as agonists or antagonists to the calcium channels.

Abstract: Compounds of the formula and their salts, wherein Cy represents cyclohexyl; Y is CH?CH?, CH?2, ? or Cy, X is trivalent straight-chain alkylene (3–10C) or trivalent straight-chain 1-alkenylene (3–10C) optionally substituted by oxo at the C adjacent N when n is 0 and Y is ?2CH; and is otherwise trivalent straight-chain alkylene (5–10C) or trivalent straight-chain 1-alkenylene (5–10C) optionally substituted by oxo at the C adjacent N; Z is N, NCO, CHNCOR1 or CHNR1, wherein R1 is alkyl (1–6C); and n is 0–5; wherein each ? and Cy independently may optionally be substituted by alkyl (1–6C) or by halo, CF3, OCF3, NO2, NR2, OR, SR, COR, COOR, CONR2, NROCR or OOCR where R is H or alkyl (1–4C), or two substituents may form a 5–7 membered ring with the proviso that the compounds of formula (1) contain at least one aromatic moiety, are useful as calcium channel blockers.

Abstract: Certain piperazine substituted compounds are described which are useful in altering calcium channel activity.

Abstract: Certain piperazine substituted compounds are described which are useful in altering calcium channel activity.

Abstract: Certain piperazine substituted compounds are described which are useful in altering calcium channel activity.

Abstract: Certain piperazine substituted compounds are described which are useful in altering calcium channel activity.

Abstract: Certain piperazine substituted compounds are described which are useful in altering calcium channel activity.

Abstract: Compounds of the formula and their salts, wherein Cy represents cyclohexyl; Y is CH═CH&PHgr;, CH&PHgr;2, &PHgr; or Cy, X is trivalent straight-chain alkylene (3-10C) or trivalent straight-chain 1-alkenylene (3-10C) optionally substituted by oxo at the C adjacent N when n is 0 and Y is &PHgr;2CH; and is otherwise trivalent straight-chain alkylene (5-10C) or trivalent straight-chain 1-alkenylene (5-10C) optionally substituted by oxo at the C adjacent N; Z is N, NCO, CHNCOR1 or CHNR1, wherein R1 is alkyl (1-6C); and n is 0-5; wherein each &PHgr; and Cy independently may optionally be substituted by alkyl (1-6C) or by halo, CF3, OCF3, NO2, NR2, OR, SR, COR, COOR, CONR2, NROCR or OOCR where R is H or alkyl (1-4C), or two substituents may form a 5-7 membered ring with the proviso that the compounds of formula (1) contain at least one aromatic moiety, are useful as calcium channel blockers.

Abstract: Compounds of the formula or the salts thereof, wherein each Z is independently N or CH, but one Z must be N; wherein n1 is 1 and n2 is 0 or 1; X1 and X2 are linkers; Ar represents one or two substituted or unsubstituted aromatic or heteroaromatic rings, and Cy represents one or two substituted or unsubstituted aliphatic cyclic or heterocyclic rings, or consists of one substituted or unsubstituted aliphatic cyclic or heterocyclic ring and one substituted or unsubstituted aromatic or heteroaromatic ring; each of Ya and Yb is two substituted or unsubstituted aromatic or heteroaromatic rings, or can be two substituted or unsubstituted aliphatic cyclic or heterocyclic rings or consists of one substituted or unsubstituted aliphatic cyclic or heterocyclic ring and one substituted or unsubstituted aromatic or heteroaromatic ring; with the proviso that said rings cannot both be phenyl when both Ar includes a single phenyl ring and X1 contains less than 5C; and with the proviso that formula (1

Abstract: Compounds of the formula and their salts, wherein Cy represents cyclohexyl; Y is CH═CH&PHgr;, CH&PHgr;2, &PHgr; or Cy, X is trivalent straight-chain alkylene (3-10C) or trivalent straight-chain 1-alkenylene (3-10C) optionally substituted by oxo at the C adjacent N when n is 0 and Y is &PHgr;2CH; and is otherwise trivalent straight-chain alkylene (5-10C) or trivalent straight-chain 1-alkenylene (5-10C) optionally substituted by oxo at the C adjacent N; Z is N, NCO, CHNCOR1 or CHNR1, wherein R1 is alkyl (1-6C); and n is 0-5; wherein each &PHgr; and Cy independently may optionally be substituted by alkyl (1-6C) or by halo, CF3, OCF3, NO2, NR2, OR, SR, COR, COOR, CONR2, NROCR or OOCR where R is H or alkyl (1-4C), or two substituents may form a 5-7 membered ring with the proviso that the compounds of formula (1) contain at least one aromatic moiety, are useful as calcium channel blockers.

Abstract: Compounds of the formula or salts thereof, wherein the variable are as defined herein are useful as calcium channel blockers.

Abstract: Compounds comprising a straight backbone carbon chain of 8-16C, optionally substituted with 1-5 alkyl groups (1-6C); said chain optionally functionalized at one terminus with halo, —OR, —SR, —NR2, —OOCR, —NROCR wherein R is alkyl (1-6C), or phosphate or pyrophosphate, or functionalized wherein a terminal carbon is optionally in the form of —COOR, —CONR2 or —COR wherein R is alkyl (1-6C); and wherein said chain may optionally contain 1-&pgr;-bonds or the epoxides thereof are useful as calcium channel inhibitors. Libraries of these compounds can also be used to identify antagonists for other targets.

Abstract: Compounds of the formula ##STR1## wherein m is 0, 1 or 2; wherein when m is 0, Z is O, when m is 1, Z is N, and when m is 2, Z is C;Y is H, OH, NH.sub.2, or an organic moiety of 1-20C, optionally additionally containing 1-8 heteroatoms selected from the group consisting of N, P, O, S and halo;each I.sup.1 and I.sup.2 is independently 0-5;I.sup.3 is 0 or 1;each of R.sup.1, R.sup.2 and R.sup.3 is independently alkyl (1-6C), aryl (6-10C) or arylalkyl (7-16C) optionally containing 1-4 heteroatoms selected from the group consisting of halo, N, P, O, and S or each of R.sup.1 and R.sup.2 may independently be halo, COOR, CONR.sub.2, CF.sub.3, CN or NO.sub.2, wherein R is H or lower alkyl (1-4C) or alkyl (1-6C);n is 0 or 1;X is a linker;with the proviso that Y is not a tropolone, a coumarin, or an antioxidant containing an aromatic group and with the further proviso that if I.sup.3 is 0, and either I.sup.1 and I.sup.2 is 0 or 1 and if R.sup.1 and/or R.sup.

Abstract: Pro-cytotoxic drug conjugates for anticancer therapy comprising a homing agent first moiety, a spacer molecule second moiety covalently linked to the homing agent, and a third moiety covalently linked to the second moiety consisting of a pro-cytotoxic drug that is non-toxic extracellularly but that, after internalization of the conjugate by proliferating tumor cells, is metabolized by one or more endogenous intracellular enzymes to a cytotoxic metabolic product, so that cell growth is arrested or the cells killed. Preferred procytotoxic drugs are carboxyphosphamide or carboxyisophosphamide.