1,3-Dihydro-1-[3-(1-piperidinyl)propyl]-2H-benzimidazol-2-ones and related compounds
AssigneeJanssen Pharmaceutica NV
InventorsJan Vandenberk, Ludo E. J. Kennis, Marcel J. M. C. Van der Aa, Albert H. M. Th. Van Heertum
Life of this patent
Estimating the term…
Abstract
Compounds of the class of 1-(benzazolyalkyl)piperidine derivatives useful as antiemetic agents.
Claims15
A chemical compound selected from the group consisting of a 1-(benzazolylalkyl)piperidine derivative having the formula:
- ##STR57## and the pharmaceutically acceptable acid addition salts thereof, wherein:
- R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- B is a member selected from the group consisting of the bivalent radicals ##STR58## said L being a member selected from the group consisting of hydrogen, lower alkyl, lower alkylcarbonyl and lower alkenyl, and said bivalent radicals being attached to the benzene nucleus with their heteroatom;
- R.sup.3 is a member selected from the group consisting of hydrogen and methyl;
- m and n are each an integer of from 1 to 2 inclusive;
- and the radical ##STR59## is a member selected from the group consisting of:
- a. a radical having the formula:
- ##STR60## wherein R.sup.4 is a member selected from the group consisting of hydrogen and lower alkyl;
- and R.sup.5 and R.sup.6 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- b. a radical having the formula:
- ##STR61## wherein R.sup.7 and R.sup.8 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- Y is a member selected from the group consisting of O and S;
- M is a member selected from the group consisting of hydrogen, lower alkyl and lower alkylcarbonyl;
- and the dotted line indicates that the double bond between the 3 and 4 carbon atoms of the piperidine nucleus is optional, provided that when said Y is S, then there is a single bond between said 3 and 4 carbon atoms of the piperidine nucleus, and then said M is hydrogen;
- c. a radical having the formula:
- ##STR62## wherein R.sup.7 and R.sup.8 are each independently selected from the group consisting of hydrogen, halo, lower alkyl, and trifluoromethyl;
- and
- d. a radical having the formula:
- ##STR63## wherein R.sup.9 is selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl, and R.sup.10 is selected from the group consisting of hydrogen and halo.
A chemical compound selected from the group consisting of 5-chloro-1-{1-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)-propyl]-4-piperi dinyl}-1,3-dihydro-2H-benzimidazol-2-one and the pharmaceutically acceptable acid addition salts thereof.
A chemical compound selected from the group consisting of 8-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl]-1-(4-fluorophenyl)-1, 3,8-triazaspiro[4,5]decan-4-one and the pharmaceutically acceptable acid addition salts thereof.
A pharmaceutical composition comprising an inert carrier material and as an active ingredient an effective antiemetic amount of a chemical compound selected from the group consisting of a 1-(benzazolylalkyl)piperidine derivative having the formula:
- ##STR64## and the pharmaceutically acceptable acid addition salts thereof, wherein:
- R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- B is a member selected from the group consisting of the bivalent radicals ##STR65## said L being a member selected from the group consisting of hydrogen, lower alkyl, lower alkylcarbonyl and lower alkenyl, and said bivalent radicals being attached to the benzene nucleus with their heteroatom;
- R.sup.3 is a member selected from the group consisting of hydrogen and methyl;
- m and n are each an integer of from 1 to 2 inclusive;
- and the radical ##STR66## is a member selected from the group consisting of:
- a. a radical having the formula:
- ##STR67## wherein R.sup.4 is a member selected from the group consisting of hydrogen and lower alkyl;
- and R.sup.5 and R.sup.6 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- b. a radical having the formula:
- ##STR68## wherein R.sup.7 and R.sup.8 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- Y is a member selected from the group consisting of O and S;
- M is a member selected from the group consisting of hydrogen, lower alkyl and lower alkylcarbonyl;
- and the dotted line indicates that the double bond between the 3 and 4 carbon atoms of the piperidine nucleus is optional, provided that when said Y is S, then there is a single bond between said 3 and 4 carbon atoms of the piperidine nucleus, and the said M is hydrogen;
- c. a radical having the formula:
- ##STR69## wherein R.sup.7 and R.sup.8 are each independently selected from the group consisting of hydrogen, halo, lower alkyl, and trifluoromethyl;
- and
- d. a radical having the formula:
- ##STR70## wherein R.sup.9 is selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl, and R.sup.10 is selected from the group consisting of hydrogen and halo.
A pharmaceutical composition in dosage unit form comprising per dosage unit an effective antiemetic amount of a compound selected from the group consisting of a 1-(benzazolylalkyl)piperidine derivative having the formula:
- ##STR71## and the pharmaceutically acceptable acid addition salts thereof, wherein:
- R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- B is a member selected from the group consisting of the bivalent radicals ##STR72## said L being a member selected from the group consisting of hydrogen, lower alkyl, lower alkylcarbonyl and lower alkenyl, and said bivalent radicals being attached to the benzene nucleus with their heteroatom;
- R.sup.3 is a member selected from the group consisting of hydrogen and methyl;
- m and n are each an integer of from 1 to 2 inclusive;
- and
- the radical ##STR73## is a member selected from the group consisting of:
- a. a radical having the formula:
- ##STR74## wherein R.sup.4 is a member selected from the group consisting of hydrogen and lower alkyl;
- and R.sup.5 and R.sup.6 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- b. a radical having the formula:
- ##STR75## wherein R.sup.7 and R.sup.8 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- Y is a member selected from the group consisting of O and S;
- M is a member selected from the group consisting of hydrogen, lower alkyl and lower alkylcarbonyl;
- and the dotted line indicates that the double bond between the 3 and 4 carbon atoms of the piperidine nucleus is optional, provided that when said Y is S, then there is a single bond between said 3 and 4 carbon atoms of the piperidine nucleus, and then said M is hydrogen;
- c. a radical having the formula:
- ##STR76## wherein R.sup.7 and R.sup.8 are each independently selected from the group consisting of hydrogen, halo, lower alkyl, and trifluoromethyl;
- and
- d. a radical having the formula:
- ##STR77## wherein R.sup.9 is selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl, and R.sup.10 is selected from the group consisting of hydrogen and halo;
- in admixture with a pharmaceutical carrier.
A pharmaceutical composition in dosage unit form comprising per dosage unit an effective antiemetic amount of 5-chloro-1-{1-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl]-4-piperid inyl}1,3-dihydro-2-H-benzimidazol-2-one and the pharmaceutically acceptable acid addition salts thereof in admixture with a pharmaceutical carrier.
A pharmaceutical composition of dosage unit form comprising per dosage unit an effective antiemetic amount of 8-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl]-1-(4-fluorophenyl)1,3 ,8-triazaspiro[4,5]decan-4-one and the pharmaceutically acceptable acid addition salts thereof in admixture with a pharmaceutical carrier.
A method of inhibiting emesis which comprises the systemic administration in warm-blooded animals of an effective antiemetic amount of a compound selected from the group consisting of a 1-(benzazolylalkyl)piperidine derivative having the formula:
- ##STR78## and the pharmaceutically acceptable acid addition salts thereof, wherein:
- R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- B is a member selected from the group consisting of the bivalent radicals ##STR79## said L being a member selected from the group consisting of hydrogen, lower alkyl, lower alkylcarbonyl and lower alkenyl, and said bivalent radicals being attached to the benzene nucleus with their heteroatom;
- R.sup.3 is a member selected from the group consisting of hydrogen and methyl
- m and n are each an integer of from 1 to 2 inclusive;
- and the radical ##STR80## is a member selected from the group consisting of:
- a. a radical having the formula:
- ##STR81## wherein R.sup.4 is a member selected from the group consisting of hydrogen and lower alkyl;
- and R.sup.5 and R.sup.6 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- b. a radical having the formula:
- ##STR82## wherein R.sup.7 and R.sup.8 are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl;
- Y is a member selected from the group consisting of O and S;
- M is a member selected from the group consisting of hydrogen, lower alkyl and lower alkylcarbonyl;
- and the dotted line indicates that the double bond between the 3 and 4 carbon atoms of the piperidine nucleus is optional, provided that when said Y is S, then there is a single bond between said 3 and 4 carbon atoms of the piperidine nucleus, and then said M is hydrogen;
- c. a radical having the formula:
- ##STR83##
- wherein R.sup.7 and R.sup.8 are each independently selected from the group consisting of hydrogen, halo, lower alkyl, and trifluoromethyl;
- and
- d. a radical having the formula:
- ##STR84## wherein R.sup.9 is selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl, and R.sup.10 is selected from the group consisting of hydrogen and halo;
- in admixture with a pharmaceutical carrier.
A method of inhibiting emesis which comprises the systemic administration in warm-blooded animals of an effective antiemetic amount of 5-chloro-1-{1-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl]-4-pipe ridinyl}-1,3-dihydro-2H-benzimidazol-2-one and the pharmaceutically acceptable acid addition salts thereof in admixture with a pharmaceutical carrier.
A method of inhibiting emesis which comprises the systemic administration in warm-blooded animals of an effective antiemetic amount of 8-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)-propyl]-1-(4-fluorophenyl )-1,3,8-triazaspiro[4,5]decan-4-one and the pharmaceutically acceptable acid addition salts thereof in admixture with a pharmaceutical carrier.
Dependencies are inferred from the claim text.