Dimerizing agents, their production and use

• US 6,984,635 B1
• Filed: 02/12/1999
• Issued: 01/10/2006
• Est. Priority Date: 02/13/1998
• Status: Expired due to Term

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation), Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Crabtree, Gerald R., Schreiber, Stuart L., Liberles, Stephen D.
• Primary Examiner(s): Huang, Evelyn Mei
• Application Number:
  US09/248,755
• Time in Patent Office: 2,524 Days
• Field of Search: 540/456, 514/291, 514/183
• US Class Current: 514/183
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07D 498/18 Bridged systems

Abstract

Materials and methods are disclosed for regulation of biological events such as target gene transcription and growth, proliferation or differentiation of engineered cells.

Claims

1. A compound selected from the group consisting of one of the following structures:

wherein RC3 is an allyl or methallyl moiety, optionally substituted with one or more groups selected from —

OH, —

SH, —

CHO, ═

O, —

COOH, oxime, —

NH₂, halo, trihaloalkyl, cyano, —

SO₂CF₃, —

OSO₂F, —

OS(O)₂R¹¹, —

SO₂—

NHR¹¹, —

NHSO₂R¹¹, aryl or heteroaryl;

R¹¹ is H or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

wherein each aryl moiety is a substituted or unsubstituted phenyl ring, and each heteroaryl moiety is selected from a five- or six-membered heteroaryl ring,

and each aryl or heteroaryl moiety is optionally substituted with one to five substituents selected from the group consisting of —

OH, —

SH, —

CHO, ═

O, —

COOH, oxime, —

NH₂, halo, trihaloalkyl, cyano, —

SO₂—

CF₃, —

OSO₂F, —

OS(O)₂R¹¹, —

SO₂—

NHR¹¹, —

NHSO₂R¹¹, aryl, heteroaryl, C1–

C8 alkoxy, C1 –

C8 branched or straight-chain alkyl, acyl, acyloxy, nitro, dialkoxyphenyl, trisubstituted phenyl, —

O-aliphatic-COOH, and —

O-aliphatic-NH₂,

each aliphatic moiety is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl moieties, optionally substituted with one or more substituents selected from the group consisting of —

OH, —

SH, —

CHO, ═

O, —

COOH, oxime, —

NH₂, halo, trihaloalkyl, cyano, —

SO₂—

CF₃, —

OSO₂F, OS(O)₂R¹¹, —

SO₂—

NHR¹¹, —

NHSO₂R¹¹, aryl and heteroaryl moieties, and

each heteroaliphatic moiety is an aliphatic moiety that contains one or more oxygen, sulfur, nitrogen, phosphorous or silicon atoms.

2. The compound of claim 1, wherein each optionally substituted aryl moiety is selected from the group consisting of phenyl, halophenyl, alkoxyphenyl, dialkoxyphenyl, trialkoxyphenyl, and alkylenedioxyphenyl,;

and each optionally substituted heteroaryl moiety is selected from the group consisting of thienyl, pyrrolyl, imidazolyl, pyrazolyl, furyl, isothiazolyl, furazanyl, isoxazolyl, thiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazinyll moieties.

3. A composition comprising a compound of claim 1 or 2 and one or more pharmaceutically acceptable excipients.

4. A compound of claim 1 or 2, wherein the compound is at least 95% free from other materials.

5. A compound of claim 1 or 2, wherein the compound is at least 98% free from other materials.