1-[(Heterocyclyl)-alkyl]-4-diarylmethoxy piperidine derivatives

• US 4,200,641 A
• Filed: 02/06/1978
• Issued: 04/29/1980
• Est. Priority Date: 12/21/1976
• Status: Expired due to Term

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Kennis, Ludo E. J., Vandenberk, Jan, Van der Aa, Marcel J. M. C., Van Heertum, Albert H. M. Th.
• Primary Examiner(s): Coughlan, Jr., Paul M.
• Application Number:
  US05/875,342
• Time in Patent Office: 813 Days
• Field of Search: 260/293.67, 260/293.68, 260/293.7, 424/267, 546/198, 546/199
• US Class Current: 514/318
• CPC Class Codes: C07D 211/46 having a hydrogen atom as the second substituent in position 4
• CPC Class Codes: C07D 213/26 Radicals substituted by halogen atoms or nitro radicals
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C07D 213/50 Ketonic radicals
• CPC Class Codes: C07D 235/06 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
• CPC Class Codes: C07D 235/08 Radicals containing only hydrogen and carbon atoms
• CPC Class Codes: C07D 235/18 with aryl radicals directly attached in position 2
• CPC Class Codes: C07D 235/26 Oxygen atoms
• CPC Class Codes: C07D 235/28 Sulfur atoms
• CPC Class Codes: C07D 295/073 with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain

Abstract

Novel 1-[(heterocyclyl)alkyl]-4-diarylmethoxy piperidine derivatives are disclosed having the formula ##STR1## where n is 2-6, Ar¹ and Ar² are aryl and B is a substituted benzimidazolyl radical. These compounds are useful for their antianaphylactic and antihistaminic properties. Specific claimed compounds are 1-{3-[4-(diphenylmethoxy)-1-piperidinyl]-propyl}-1,3-dihydro-2H-benzimidazol-2-one, 1-{2-[4-(diphenylmethoxy)-1-piperidinyl]ethyl}1-, 3-dihydro-2H-benzimidazol-2-one, and 1-{4-[4-(diphenylmethoxy)-1-piperidinyl]butyl}-1,3-dihydro-2H-benzimidazol-2-one.

Claims

1. A chemical compound selected from the group consisting of a compound having the formula ##STR61## and the pharmaceutically acceptable acid addition salts thereof, wherein:

Ar¹ and Ar² are each independently selected from the group consisting of phenyl, substituted phenyl and pyridinyl, wherein said substituted phenyl is phenyl having from 1 to 2 substituents independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, trifluoromethyl and nitro;

m is the ingeger 1;

A is >

CH--

n is an integer of from 2 to 6 inclusive, provided that when C_n H_2n represents a branched alkylene chain, then at least 2 carbon atoms are present in the linear portion of the chain linking B with the piperidine nitrogen atom; and

B is a member selected from the group consisting of;

(a) a radical having the formula ##STR62## wherein;

R¹ and R² are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl; and

Y is a member selected from the group consisting of oxygen, sulfur and a substituted nitrogen of the formula >

N--L wherein said L is a member selected from the group consisting of hydrogen, lower alkyl, lower alkylcarbonyl, lower alkyloxycarbonyl-lower alkyl, carboxy-lower alkyl, phenyl, phenylmethyl, lower alkylaminocarbonyl, hydroxymethyl, and lower alkenyl; and

(b) a radical having the formula ##STR63## wherein;

R¹ and R² are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl; and

M is a member selected from the group consisting of hydrogen, lower alkyl, phenyl, phenylmethyl, mercapto, lower alkylthio, amino, lower alkylcarbonylamino, lower alkyloxycarbonylamino, and cycloalkyl having from 3 to 6 carbon atoms.

2. A chemical compound selected from the group consisting of 1-{3-[4-(diphenylmethoxy)-1-piperidinyl]-propyl}-1,3-dihydro-2H-benzimidazol-2-one and the pharmaceutically acceptable acid addition salts thereof.

3. A chemical compound selected from the group consisting of 1-{2-[4-(diphenylmethoxy)-1-piperidinyl]ethyl}-1,3-dihydro-2H-benzimidazol-2-one and the pharmaceutically acceptable acid addition salts thereof.

4. A chemical compound selected from the group consisting of 1-{4-[4-(diphenylmethoxy)-1-piperidinyl]butyl}-1,3-dihydro-2H-benzimidazol-2-one and the pharmaceutically acceptable acid addition salts thereof.

5. A pharmaceutical composition comprising an inert carrier material and as an active ingredient an effective antihistaminic or anti-anaphylactic amount of a chemical compound selected from the group consisting of a compound having the formula ##STR64## and the pharmaceutically acceptable acid addition salts thereof, wherein:

Ar¹ and Ar² are each independently selected from the group consisting of phenyl, substituted phenyl and pyridinyl, wherein said substituted phenyl is phenyl having from 1 to 2 substituents independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, trifluoromethyl and nitro;

m is the integer 1;

A is >

CH--

n is an integer of from 2 to 6 inclusive, provided that when C_n H_2n represents a branched alkylene chain, then at least 2 carbon atoms are present in the linear portion of the chain linking B with the piperidine nitrogen atom; and

B is a member selected from the group consisting of;

(a) a radical having the formula ##STR65## wherein;

R¹ and R² are each independently selected from the group consisting of hydrogen, halo, lower alkyl and trifluoromethyl; and

Y is a member selected from the group consisting of oxygen, sulfur and a substituted nitrogen of the formula >

N--L wherein said L is a member selected from the group consisting of hydrogen, lower alkyl, lower alkylcarbonyl, lower alkyloxycarbonyl-lower alkyl, carboxy-lower alkyl, phenyl, phenylmethyl, lower alkylaminocarbonyl, hydroxymethyl, and lower alkenyl; and

(b) a radical having the formula ##STR66## wherein;

R¹ and R² are each independently selected from the group consisting of hydrogen, halo, lower alkyl, and trifluoromethyl; and

M is a member selected from the group consisting of hydrogen, lower alkyl, phenyl, phenylmethyl, mercapto, lower alkylthio, amino, lower alkylcarbonylamino, lower alkyloxycarbonylamino, and cycloalkyl having from 3 to 6 carbon atoms.