# US 5,705,514 A · Signal transduction inhibitor compounds > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,705,514 A - Document ID: US5705514A - Status: Granted - Kind: A - Application number: 08/455,825 - Filed: 1995-05-31 - Granted: 1998-01-06 - Earliest claimed: 1989-05-19 - Assignees: The United States of America as represented by the Department of Health and Human Services - Inventors: Elise C. Kohn; Lance A. Liotta; Christian C. Felder - Web page: https://patentgrep.com/patent/US5705514A ## CPC - A61K 31/4164: 1,3-Diazoles - A61K 31/12: Ketones - A61K 31/41: having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole - A61K 31/415: 1,2-Diazoles - A61K 31/4192: 1,2,3-Triazoles - A61P 35/00: Antineoplastic agents - C07D 233/90: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals - C07D 249/04: 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract A method of inhibiting the invasion and metastasis of malignant solid tumors in mammals, said method comprising administering to said mammal an anti-proliferative, anti-invasive and anti-metastasis effective amount of a compound selected from the group of formulas consisting of: ##STR1## wherein: p is an integer of from 0 to 4; Ar.sup.1 is a moiety selected from the group consisting of --Ar.sup.2 --X--Ar.sup.3, phenyl, trioxaadamantyl, anthracenyl, anthraquinonyl, naphthyl, phenanthryl, and substituted versions thereof; Ar.sup.2 and Ar.sup.3 are each aromatic moieties independently selected from the group consisting of phenyl, naphthyl, and substituted versions thereof; X is a linking moiety selected from the group consisting of O, S, SO.sub.2 2, CO, CHCN, straight chain alkyl, alkoxy, and alkoxyalkyl; and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl and substituted versions thereof, said heterocyclic moieties being attached to the --(CH.sub.2).sub.p -- portion of the molecule at the N1 position of the heterocycle. ## Claims ### Claim 1 A method of inhibiting the invasion and metastasis of malignant solid tumors in mammals, said method comprising administering to said mammal an anti-proliferative, anti-invasive and anti-metastasis effective amount of a compound selected from the group of formulas consisting of: ##STR13## wherein: p is an integer of from 0 to 4; Ar.sup.1 is a moiety selected from the group consisting of --Ar.sup.2 --X--Ar.sup.3, phenyl, trioxaadamantyl, anthracenyl, anthraquinonyl, naphthyl, phenanthryl, and substituted versions thereof; Ar.sup.2 and Ar.sup.3 are each aromatic moieties independently selected from the group consisting of phenyl, naphthyl, and substituted versions thereof; X is a linking moiety selected from the group consisting of O, S, SO.sub.2, CO, CHCN, straight chain alkyl, alkoxy, and alkoxyalkyl; and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl and substituted versions thereof, said heterocyclic moiety being attached to the --(CH.sub.2).sub.p -- portion of the molecule at the N1 position of the heterocycle. ### Claim 2 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I). ### Claim 3 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), Ar.sup.1 is --Ar.sup.2 --X--Ar.sup.3, Ar.sup.2 and Ar.sup.3 are both substituted phenyl, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, 1,2,3-triazolyl, and substituted versions thereof. ### Claim 4 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), p is an integer of from 0 to 2, Ar.sup.1 is --Ar.sup.2 --X--Ar.sup.3, Ar.sup.2 and Ar.sup.3 are both substituted phenyl, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, and 1,2,3-triazolyl, and substituted versions thereof. ### Claim 5 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), p is an integer of from 0 to 2, Ar.sup.1 is --Ar.sup.2 --X--Ar.sup.3, Ar.sup.2 and Ar.sup.3 are both substituted phenyl, X is a linking moiety selected from the group consisting of O, CO, and CHCN, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, and 1,2,3-triazolyl, and substituted versions thereof. ### Claim 6 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), p is 1, Ar.sup.1 is --Ar.sup.2 --X--Ar.sup.3, Ar.sup.2 and Ar.sup.3 are both substituted phenyl, X is CO, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, and 1,2,3-triazolyl, and substituted versions thereof. ### Claim 7 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), p is 1, Ar.sup.1 is --Ar.sup.2 --X--Ar.sup.3, Ar.sup.2 and Ar.sup.3 are both substituted phenyl, X is CO, and Z is 5-amino-4-carboxamido-1,2,3-triazolyl. ### Claim 8 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), p is 1, Ar.sup.1 is --Ar.sup.2 --X--Ar.sup.3, Ar.sup.2 is 2,6-dichlorophenyl, Ar.sup.3 is 4-chlorophenyl, X is CO, and Z is 5-amino-4-carboxamido-1,2,3-triazolyl. ### Claim 9 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), Ar.sup.1 is a moiety selected from the group consisting of trioxaadamantyl, anthracenyl, anthraquinonyl, naphthyl, and phenyl and substituted versions thereof, Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, 1,2,3-triazolyl, and substituted versions thereof. ### Claim 10 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), p is 1, Ar.sup.1 is trioxaadamantyl, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, and 1,2,3-triazolyl, and substituted versions thereof. ### Claim 11 (depends on 1) A method m accordance with claim 1 wherein said compound is of formula (I), p is 1, Ar.sup.1 is 10-chloro-9-anthracenyl, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, and 1,2,3-triazolyl, and substituted versions thereof. ### Claim 12 (depends on 1) A method m accordance with claim 1 wherein said compound is of formula (I), p is 1, Ar.sup.1 is 2-anthraquinonyl, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, and 1,2,3-triazolyl, and substituted versions thereof. ### Claim 13 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), p is 1, Ar.sup.1 is phenyl or substituted phenyl, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, and 1,2,3-triazolyl, and substituted versions thereof. ### Claim 14 (depends on 1) A method in accordance with claim 1 wherein said compound is of formula (I), p is 1, Ar.sup.1 is naphthyl or substituted naphthyl, and Z is a nitrogen-containing heterocyclic moiety selected from the group consisting of imidazolyl, and 1,2,3-triazolyl, and substituted versions thereof.