Methods for the chemical synthesis of pyrrole-linked bivalent compounds, and compositions thereof
AssigneeAvekshan, LLC.
InventorJohn CRAN
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Abstract
The present invention in various aspects relates to the synthesis of pyrrole-linked bivalent compounds, including but not limited to norBNI, as well as pharmaceutical compositions comprising the same.
Claims58
A process for a chemical synthesis of a compound having the structure of Formula (I):
- or a salt thereof, wherein:
- Ra is hydrogen or a substituent;
- each n is an integer independently selected from 0, 1, 2, 3, and 4;
- each r is an integer ranging from 0 to (2n+4);
- and
- each R is an independently selected substituent, wherein two or more neighboring R groups may optionally form a hydrocarbon or heterocyclic ring system;
- the process comprising reacting one or more compounds of Formula II:
- with a hydrazine reagent under reaction conditions sufficient to produce the compound of Formula (I), wherein R, r and n have the same meaning as described with respect to Formula (I) and Z is O, S, or NRf, wherein Rf is hydrogen or a substituent.
A process for a chemical synthesis of a compound having the structure of Formula (I):
- or a salt thereof, wherein:
- Ra is hydrogen or a substituent;
- each n is an integer independently selected from 0, 1, 2, 3, and 4;
- each r is an integer ranging from 0 to (2n+4);
- and
- each R is an independently selected substituent, wherein two or more neighboring R groups may optionally form a hydrocarbon or heterocyclic ring system;
- the process comprising reacting one or more compounds of Formula II:
- with an N-aminoimide reagent under reaction conditions sufficient to produce the compound of Formula (I) with a yield of at least 75%, wherein R, r and n have the same meaning as described with respect to Formula (I) and Z is O, S, or Me, wherein Rf is hydrogen or a substituent.
A pharmaceutical composition comprising a pharmaceutically acceptable salt of norBNI selected from tartrate, citrate, diacetate, sulfate or phosphate, and a pharmaceutically acceptable carrier.
A norBNI composition that is at least 99% norBNI or salt thereof, with respect to norBNI and reaction impurities as 100%, or at least 99.5% norBNI or salt thereof with respect to norBNI and reaction impurities as 100%.
Dependencies are inferred from the claim text.