High throughput HPLC method for determining Log P values

• US 6,524,863 B1
• Filed: 07/26/2000
• Issued: 02/25/2003
• Est. Priority Date: 08/04/1999
• Status: Expired due to Fees

• Current Assignee: Scynexis Incorporated
• Original Assignee: SCYNEXIS Chemistry & Automation, Inc.
• Inventors: Abedi, Jaleh
• Primary Examiner(s): LUDLOW, JAN M
• Application Number:
  US09/625,905
• Time in Patent Office: 944 Days
• Field of Search: 436/161, 73/615.2, 73/615.6, 210/656, 210/662
• US Class Current: 506/12
• CPC Class Codes: G01N 30/34 of fluid composition, e.g. gradient G01N30/36 takes precedence
• CPC Class Codes: G01N 30/8672 not depending on an individual instrument, e.g. retention time indexes or calibration transfer
• CPC Class Codes: G01N 30/8682 Group type analysis, e.g. of components having structural properties in common
• CPC Class Codes: G01N 30/88 Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
• CPC Class Codes: G01N 30/89 Inverse chromatography

Abstract

Methods for calculating Log P values for organic compounds are disclosed. The methods allow identification of compounds in a library with a desired Log P value. The method can be used to minimize the number of compounds in a given combinatorial or lead generation library which need to be further characterized and/or assayed. The Log P value is preferably obtained while the purity of the compounds is being determined. Preferably, the Log P value is correlated to the retention time on an HPLC column, such that the retention time equals the Log P value.

Claims

1. A method for calculating log P values for one or more compounds, comprising:

a) determining an appropriate set of HPLC conditions such that the log P value is substantially equal to the retention time on an HPLC column, and

b) determining the log P values of one or more compounds by eluting them off of the HPLC column under the set of HPLC conditions determined in step (a).

2. The method of claim 1 wherein the purity of the compound or compounds and the Log P value(s) are determined simultaneously.

3. The method of claim 1 wherein the compounds to be analyzed are present in a combinatorial or lead generation library.

4. The method of claim 1 wherein the compounds are detected and/or characterized by one or more methods selected from the group consisting of UV, MS and ELSD.

5. The method of claim 1, wherein the one or more compounds are eluted off of the HPLC column using gradient elution.

6. A method for calculating log P values for one or more compounds, comprising:

a) determining an appropriate set of HPLC conditions such that the log P value is substantially equal to the retention time on an HPLC column;

b) determining the log P values of one or more compounds by eluting them off of the HPLC column under the set of HPLC conditions determined in step (a); and

c) characterizing the one or more compounds, wherein only the one or more compounds with a desired log P value are characterized.

7. The method of claim 6, wherein characterizing the one or more compounds comprises performing a bioassay on the one or more compounds to determine their bioactivity and wherein only the one or more compounds with a desired Log P value are bioassayed.

8. The method of claim 6, wherein information regarding the Log P values and the characterization of the one or more compounds is stored in a database.

9. The method of claim 6, wherein the one or more compounds are eluted off of the HPLC column using gradient elution.

10. The method of claim 6, wherein purity of the one or more compounds is determined simultaneously with the log P values of the one or more compounds.

11. The method of claim 7, wherein the one or more compounds are eluted off of the HPLC column using gradient elution and wherein information regarding the Log P values and the bioactivity of the one or more compounds is stored in a database.

12. The method of claim 11, wherein purity of the one or more compounds is determined simultaneously with the log P values of the one or more compounds.