Low molecular weight dendritic compounds as pharmaceutical agents

• US 6,225,352 B1
• Filed: 02/04/1999
• Issued: 05/01/2001
• Est. Priority Date: 08/14/1996
• Status: Expired due to Fees

• Current Assignee: Warner-Lambert Company (Pfizer Inc.)
• Original Assignee: Warner-Lambert Company (Pfizer Inc.)
• Inventors: Ratcliffe, Giles Stuart, Horwell, David Christopher
• Primary Examiner(s): AULAKH, CHARANJIT
• Application Number:
  US09/230,988
• Time in Patent Office: 817 Days
• Field of Search: 514/415, 514/617, 514/622, 548/491, 564/180
• US Class Current: 514/617
• CPC Class Codes: C07C 217/58 with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• CPC Class Codes: C07C 235/66 with carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings being part of condensed ring systems and singly-bound oxygen atoms, bound to the same carbon skeleton
• CPC Class Codes: C07C 237/04 the carbon skeleton being acyclic and saturated
• CPC Class Codes: C07C 237/22 having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated peptides C07K
• CPC Class Codes: C07C 239/20 having oxygen atoms of hydroxylamino groups etherified
• CPC Class Codes: C07C 257/18 having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 43/2055 containing more than one ether bond
• CPC Class Codes: C07C 43/23 containing hydroxy or O-metal groups
• CPC Class Codes: C07C 69/94 of polycyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07D 209/14 Radicals substituted by nitrogen atoms, not forming part of a nitro radical

Abstract

This invention is for low molecular weight dendritic polymers (dendroids) of Formula I

are useful as agents in the treatment of cancer, Alzheimers disease, thrombosis, inflammatory diseases, and bacterial resistance.

Claims

1. A compound of formula

or a pharmaceutically acceptable salt thereof wherein:

A is selected from [1,2,3,5-tetrasubstituted or 1,2,4- or 1,3,5-trisubstituted benzene;

2,3,4,5-tetrasubstituted or 2,3,5;

or 2,4,5-trisubstituted thiophenes;

2,3,4,6- or 2,4,5,6-tetrasubstituted or 2,3,5-;

or 2,3,6-trisubstituted pyridine;

] 1,8,X-trisubstituted naphthalene, ortho-, meta-, or perisubstituted naphthalene;

B, C, and D are covalently bonded to A and are the same or different and are independently selected from —

Y—

Z—

below;

Y is selected from ═

(CH₂)_n—

O—

, O—

(CH₂)_n—

, —

NHCO(CH₂)_n, (CH₂)_nNHCO—

, CONH-(CH₂)_n, (CH₂)_nCONH;

—

(CH₂)_n—

, or a bond wherein n is an integer of from 0 to 3.

Z is di, tri, or tetrasubstituted benzene as defined above or is selected from A above, or is a substituted amine or amide selected from —

CH₂-3-indole and —

CH₂-2-imidazole or a carbamate, or a bond;

E, F, G, H, I, J, K, L, and M are each independently selected from B, C, and D above;

X is hydrogen, (CH₂)_nCO₂R wherein R is an ester;

N or a function group attached to the one monomer A above.

2. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 together with a pharmaceutically acceptable carrier.

3. A method for the treatment of bacterial infections comprising administering to a mammal in need of said treatment a therapeutically effective amount of a compound of claim 1.

4. A compound according to claim 1 and selected from:

8-(4-Bromo-benzyloxy)-naphthalene-1-carboxylic acid dimethylamide;

8-(4-Methoxy-benzyloxy)-naphthalene-1-carboxylic acid dimethylamide;

8-(3,4-Dimethoxy-benzyloxy)-naphthalene-1-carboxylic acid dimethylamide;

8-(3,4,5-Trimethoxy-benzyloxy)-naphthalene-1-carboxylic acid dimethylamide;

8-(3,5-Dimethoxy-benzyloxy)-naphthalene-1-carboxylic acid dimethylamide;

8-(Biphenyl-4-ylmethoxy)-naphthalene-1-carboxylic acid dimethylamide;

8-(4-Benzyloxy-benzyloxy)-naphthalene-1-carboxylic acid dimethylamide;

8-(4-Styryl-benzyloxy)-naphthalene-1-carboxylic acid dimethylamide;

8-Hydroxy-naphthalene-1-carboxylic acid benzyl-phenethyl-amide;

8-(4-Benxyloxy-benzyloxy)-naphthalene-1-carboxylic acid benzyl-phenethyl-amide;

8-(4-Benxyloxy-benzyloxy)-naphthalene-1-carboxylic acid benzyl-ethyl-amide;

8-(4-Benxyloxy-benzyloxy)-naphthalene-1-carboxylic acid [1-(1H-indol-3-yl)-ethyl]-isoproyl-amide; and

8-(4-Benxyloxy-benzyloxy)-naphthalene-1-carboxylic acid [2-(2-methoxy-phenyl)-ethyl]-phenethyl-amide.