Methods for processing chemical compounds having reactive functional groups

• US 6,559,303 B1
• Filed: 04/09/1999
• Issued: 05/06/2003
• Est. Priority Date: 01/11/1995
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Cook, Phillip Dan
• Primary Examiner(s): Ford, John M.
• Application Number:
  US09/254,219
• Time in Patent Office: 1,488 Days
• Field of Search: 540/472
• US Class Current: 540/472
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: C07D 471/08 Bridged systems
• CPC Class Codes: C07D 515/08 Bridged systems

Abstract

Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring system. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.

Claims

1. A composition of macrocyclic compounds wherein each of said macrocyclic compounds is of the formula:

wherein

each L<sub>1−

n</sub> is, independently, a chemical functional group selected from the group consisting of L₁, L₂, L₃, to L_n wherein n is from 4 to about 20;

each L*<sub>1−

m</sub> is, independently, a chemical functional group selected from the group consisting of L*₁ to L*_m where m is 0 or from 2 to about 20; and

each L<sub>1−

n</sub> and each L*<sub>1−

m</sub> is, independently, selected from the group consisting of H, C₂-C₁₀ alkyl or substituted alkyl, C₂-C₁₀ alkenyl or substituted alkenyl, C₂-C₁₀ alkynyl or substituted alkynyl, C₄-C₇ carbocyclic alkyl, or substituted C₄-C₇ carbocyclic alkyl, alkenyl or alkynyl carbocyclic, or substituted alkenyl or alkynyl carbocyclic, or C₆-C₁₄ aryl or substituted aryl where the substituent groups are selected from hydroxyl, amino, alkoxy, alcohol, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl, or alkynyl groups;

an ether having 2 to 10 carbon atoms and 1 to 4 oxygen or sulfur atoms;

halogen;

hydroxyl;

thiol;

keto;

carboxyl;

amide;

amidine;

guanidine;

glutamyl;

nitrate;

nitro;

nitrile;

trifluoromethyl;

trifluoromethoxy;

O-alkyl;

S-alkyl;

NH-alkyl;

N-dialkyl;

O-aralkyl;

S-aralkyl;

NH-aralkyl;

amino;

azido;

hydrazino;

hydroxylamino;

sulfoxide;

sulfone;

sulfide;

disulfide; and

silyl.

2. The composition of claim 1 wherein n is from 2 to about 10.

3. The composition of claim 2 wherein n is from about 4 to about 10.

4. The composition of claim 3 wherein n is 4.

5. The composition of claim 1 wherein m is 0 or 2.

6. The composition of claim 3 wherein m is 0.

7. The composition of claim 1 wherein at least one of L₁₋

n or L*<sub>1−

m</sub> is alkyl, alkenyl, alkynyl, alicyclic, or aralkyl.

8. The composition of claim 1 wherein at least one of L₁₋

n or L*<sub>1−

m</sub> is benzyl, m-methylbenzyl, m-nitrobenzyl, m-methoxybenzyl, m-anisoyl, or and m-toluoyl.