Back to results
US 2004/0110944 A1Published application
4,7-Disubstituted indoles and methods of making
AssigneeIrm LLC
InventorsPhil B. Alper, Khanh Linh T. Nguyen
Life of this patent
Estimating the term…
Abstract
The present invention provides, compounds, methods and compositions of biologically important indoles. In addition, the present invention provides synthesis methods for substituting leaving groups at positions 4 and 7 of the indole ring as diversity generating elements.
Claims24
A compound having the formula
- 34
- wherein:
- R1 is a member selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
- R2 is a member selected from the group consisting of hydrogen, halogen, optionally substituted alkylamino, and C(O)—R5, wherein R5 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
- R3 is a member selected from the group consisting of hydrogen, and optionally substituted alkyl;
- R4 is a member selected from the group consisting of halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and S(O)n—R6, wherein R6 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl, wherein n is 1, 2 or 3;
- and
- X is a heteroatom selected from the group consisting of O and NR, wherein R is a member selected from the group consisting of hydrogen and optionally substituted alkyl, or, alternatively, R and R2 together with the atoms to which they are attached, join to form an optionally substituted 5-, 6- or 7-membered heterocyclic ring.
5 more elements
A method of making a compound having the formula:
- 40
- wherein:
- R1 is a member selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
- R2 is a member selected from the group consisting of hydrogen, halogen, optionally substituted alkylamino, and C(O)—R5, wherein R5 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
- R3 is a member selected from the group consisting of hydrogen, and optionally substituted alkyl;
- R10 is a member selected from the group consisting of halogen, and S(O)n—R wherein R6 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl, wherein n is 1, 2 or 3;
- and
- X is a heteroatom selected from 0 and NR, wherein R is a member selected from the group consisting of hydrogen and optionally substituted alkyl, or, alternatively, R and R2 together with the atoms to which they are attached, join to form an optionally substituted 5-, 6- or 7-membered heterocyclic ring, said method comprising:
- reacting a compound having the formula:
- 41
- with a sulfide to form a compound having a sulfide functionality of the formula
- 42
- wherein R9 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
- and PG is a protective group;
- cleaving said protecting group (PG) to form a compound having the formula:
- 43
- protecting the primary amine to form a protected amine;
- and
- eliminating said sulfide functional group and subsequent alcoholysis to generate a compound of Formula II.
16 more elements
A method for generating a pharmacophore scaffold by introducing leaving groups at positions 4 and 7 of an indole ring, said method comprising:
- reacting a compound having the formula:
- 46
- with a sulfide to form a compound having a sulfide functionality of the formula
- 47
- wherein R9 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
- and PG is a protective group;
- cleaving said protecting group (PG) to form a compound having the formula:
- 48
- protecting the primary amine to form a protected amine;
- and
- eliminating said sulfide functional group and subsequent alcoholysis to generate a pharmacophore scaffold with leaving groups at positions 4 and 7 of the indole ring to generate a compound having a formula:
- 49
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
- R2 is a member selected from the group consisting of hydrogen, halogen, and C(O)—R5, wherein R5 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
- R3 is a member selected from the group consisting of hydrogen, and optionally substituted alkyl;
- and R10 is a member selected from the group consisting of halogen, and S(O)n—R6, wherein R6 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl, wherein n is 1, 2 or 3.
14 more elements
A method for making a compound having the formula:
- 50
- wherein:
- R11 is a member selected from the group consisting of optionally substituted alkenyl, optionally substituted aryl, and optionally substituted heteroaryl, said method comprising:
- reacting a compound having the formula
- 51
- with an sp2-sp2 C—C bond coupling group in the presence of a Pd catalyst, to generate said compound of Formula IV.
3 more elements
Dependencies are inferred from the claim text.