US5811241A
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Method for preparing and identifying N-substitued 1,4-piperazines and N-substituted 1,4-piperazinediones
Assignee: Cortech Inc
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Filing: 1995-09-13
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Granted: 1998-09-22
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Expires: 2015-09-13
Abstract
Abstract The invention provides a method of synthesizing N-substituted 1,4-piperazines and N-substituted 1,4-piperazinediones. The invention also provides a method for synthesing combinatorial libraries of piperazine derivatives which can be assayed for biological activity in pre-specified ligand binding or enzymatic activity screens.
Inventors
- 👤 Val S. Goodfellow
- 👤 Donald A. McLeod
- 👤 James Ivan Gerrity
- 👤 Christopher P. Laudeman
- 👤 Michael R. Burkard
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 22:12
CPC Classifications
C; C07; C07D; C07D295/00; C07D295/02; C07D241/00; C07D241/02; C07D241/06; C07D241/08
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
68 words
A method of synthesizing 1, 4-piperazines and derivatives thereof comprising simultaneously cyclizing and cleaving an optionally substituted glycyl residue or dipeptoid from a polymeric support further comprising, prior to cyclization and cleavage, attaching an N-protected α-amino acid to a polymeric support; deprotecting said α-amino acid; reductively alkylating said α-amino acid with an aldehyde or ketone; bromoacetylating resulting secondary amine; and reacting resulting bromoacetyl compound with a primary amine.
Claim 2
Independent Claim
68 words
A method of synthesizing 1, 4-piperazines and derivatives thereof comprising simultaneously cyclizing and cleaving an optionally substituted glycyl residue or dipeptoid from a polymeric support further comprising, prior to cyclization and cleavage, attaching an N-protected α-amino acid to a polymeric support; deprotecting said α-amino acid; reductively alkylating said α-amino acid with an aldehyde or ketone; bromoacetylating resulting secondary amine; and reacting resulting bromoacetyl compound with a primary amine.
Claim 3
Dependent Claim
25 words
The method according to claim 1 wherein said cyclization and cleavage is accomplished via heating in a non-reactive solvent in the presence of a catalyst.
Claim 4
Dependent Claim
17 words
The method according to claim 2 wherein said solvent is 2-butanol and said catalyst is acetic acid.
Claim 5
Dependent Claim
37 words
The method according to claim 1 wherein said α-amino acid is α-carbon substituted with benzyl, substituted benzyl, indole, methylnaphthyl, cyclohexyl, methylcyclohexyl, indanyl, (C1-C5) alkyloxyaryl, aminoalkyl (C1-C8), guanidino alkyl (C1-C8), alkylcarboxylic, hydroxyalkyl (C1-C5), alkylthioalkyl, (C1-C3) alkylbenzamidio or hydrogen.
Claim 6
Dependent Claim
34 words
The method according to claim 1 wherein said α-amino acid is selected from the group consisting of L- or D-Phenylanine, D- or L-Tryptophan, D- or l-Cyclohexylalanine, D- or L- β-2-Naphthylalanine, and D- or L-Indanylglycine.
Claim 7
Dependent Claim
45 words
The method according to claim 1 wherein said aldehyde is of the formula R1C(O)H, wherein R1 is cyclohexyl, methylcyclohexyl, benzyl, substituted benzyl, phenethyl, biphenyl, benzoyl, hydrogen, methylnapthyl, indanyl, guanidinoalkyl (C2-C8), aminoalkyl (C2-C8), arylalkylcarbamate with alkyl chains of C2 to C8, alkanoyl (C1-C12) or alkyl (C1-C12).
Claim 8
Dependent Claim
31 words
The method according to claim 1 wherein said aldehyde or ketone group is selected from the group consisting of cyclohexanone, cyclohexanone carboxaldehyde, benzaldehyde, phenylacetalaldehyde, 4'-biphenylcarboxaldehyde, 2-Napthaldehyde, 2-indanone-, 2-(N-Cbz)-ethanal, 6-(N-Cbz)-hexanal and 12-(N-Cbz)-dodecanal.
Claim 9
Dependent Claim
94 words
The method according to claim 1 wherein said primary amine is of the formula H2NR3 where R3 is selected from the group consisting of cyclohexyl, methylcyclohexyl, benzyl, substituted benzyl, phenethyl, biphenyl, benzoyl, hydrogen, methylnapthyl, indanyl, guanidinoalkyl (C2-C8), aminoalkyl (C2-C8), arylalkylcarbamates with alkyl chains of C2 to C8, alkanoyl (C1-C12), alkyl (C1-C12), (C2-C12)-alkylguanidinoalkyl (-C2-C8), benzamidino, (C1-C6) alkylbenzamidino, (C1-C6) alkylquinuclidine, (C1-C6) alkylpiperazine, C1 to C6 alkyl N-substituted piperazine, (C1-C6) alkylamino piperidine, (C1-C6) alkylamino N-substituted piperidine, (C1-C6) alkylcarboxyamidobenzamidino, (C1-C6) alkylcarboxamidoquinuclidine, (C1-C6) alkylcarboxamido piperazine, C1 to C6 alkylcarboxyl N-substituted piperazine, (C1-C6) alkylcarboxamidino piperidine and (C1-C6) alkylcarboxamidino N-substituted piperidine.
Claim 10
Dependent Claim
12 words
The method according to claim 1 wherein said primary amine is ##STR48##
Claim 11
Dependent Claim
14 words
The method of synthesizing piperazines according to claim 1 further comprising reducing resulting 1,4-piperazine-2,5-dione.
Claim 12
Dependent Claim
17 words
The method according to claim 10 wherein said 1,4-piperazine-2,5-dione is reduced using diborane or lithium aluminum hydride.
References Cited (Backward Citations)
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