US 9,175,044 B2Granted

Derivatives of glyco-CF2-serine and glyco-CF2-threonine

AssigneeTfchem

InventorsGeraldine Deliencourt-Godefroy, Hyacinthe Fillon, Thibaut Martin

Life of this patent

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Abstract

The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer or a mixture of stereoisomers in any proportion, in particular a mixture of enantiomers, and particularly a racemate mixture, as well as to their process of preparation, their use in the peptide synthesis, said peptide and the use of said peptide.

Claims26

Dependent claims

A compound of formula (I):

or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer or a mixture of stereoisomers in any proportion,
wherein:
Y represents a CN, NO2, NR6R7 or CH2NR6R7 group,
Z represents H or CH3,
R represents a hydrogen or fluorine atom or a CH3, CH2F, CH2OSiRa1Rb1Rc1, CH2OR8, CH2OC(O)R9, CH2OCO2R10, CH2OC(O)NR11R12, CH2OP(O)(OR13)2 or CH2OSO3R14 group,
R1 and R2 represent, independently from one another, a fluorine atom or an OSiRa2Rb2Rc2, OR15, OC(O)R16, OCO2R17, OC(O)NR18R19, OP(O)(OR20)2 or OSO3R21 group,
R3 represents a fluorine atom or an OSiRa3Rb3Rc3, OR22, OC(O)R23, OCO2R24, OCONR25R26, OP(O)(OR27)2, OSO3R28, N3, phtalimidyl, NR29R30, NR31C(O)R32, NR33C(O)OR34, N(C(O)R35)C(O)R36, N(C(O)R37)C(O)OR38 and N(C(O)OR39)C(O)OR40 group,
R4 represents a hydrogen or halogen atom or an OSiRa4Rb4Rc4, OR41, OC(O)R42, OCO2R43, OCONR44R45, OP(O)(OR46)2 or OSO3R47 group,
or R and R1, together with the carbon atoms carrying them, form a cyclic acetal having the following formula:
and/or (R1 and R2), (R2 and R3), and/or (R3 and R4), together with the carbon atoms carrying them, form a cyclic acetal having the following formula:
and
R5 represents a hydrogen or halogen atom or a R48, OR49 or NR50R51 group, with:
R6 representing:
a hydrogen atom,
a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
a C(O)R52 group, or
a C(O)OR53 group,
R7 representing:
a hydrogen atom,
a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
a C(O)R52 group,
a C(O)OR53 group, or
a N-protecting group,
R8, R15, R22 and R41 representing, independently from one another, a hydrogen atom;
an O-protecting group;
or a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl, (C1-C6)-alkyl-heteroaryl, saccharidic or polysaccharidic group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
R9, R10, R16, R17, R23, R24, R32, R34 to R40, R42, R43, R48, R52 and R53 representing, independently from one another, a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
R11, R12, R18, R19, R25, R26, R29 to R31, R33, R44, R45, R50 and R51 representing, independently from one another, a hydrogen atom or a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
R13, R14, R20, R21, R27, R28, R46 and R47 representing, independently from one another, a hydrogen atom or a (C1-C6)alkyl group,
R49 representing:
a hydrogen atom,
a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among an halogen atom, OH, COOH and CHO, or
a O-protecting group,
Ra1 to Ra4, Rb1 to Rb4 and Rc1 to Rc4 representing, independently from one another, a (C1-C6)alkyl, aryl or aryl-(C1-C6)alkyl group, and
Rd and Re representing, independently from one another, a hydrogen atom or a (C1-C6)alkyl group.

32 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/823,237Filed 22 Dec 2011
Priority: EP 1030649322 Dec 2010
Published: US 2013/0171180 A14 Jul 2013
Granted: 3 Nov 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07K 9/001
Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof: the peptide…
A01N 1/126
Preservation or perfusion media: physiologically active agents, e.g. antioxidants or nutrients
A61K 8/64
Containing organic compounds: proteins; Peptides; Derivatives or degradation products thereof
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents

Family

US 2013/0171180 A1Pre-grant publication · published 4 Jul 2013
US 9,175,044 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of formula (I):

or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer or a mixture of stereoisomers in any proportion,
wherein:
Y represents a CN, NO2, NR6R7 or CH2NR6R7 group,
Z represents H or CH3,
R represents a hydrogen or fluorine atom or a CH3, CH2F, CH2OSiRa1Rb1Rc1, CH2OR8, CH2OC(O)R9, CH2OCO2R10, CH2OC(O)NR11R12, CH2OP(O)(OR13)2 or CH2OSO3R14 group,
R1 and R2 represent, independently from one another, a fluorine atom or an OSiRa2Rb2Rc2, OR15, OC(O)R16, OCO2R17, OC(O)NR18R19, OP(O)(OR20)2 or OSO3R21 group,
R3 represents a fluorine atom or an OSiRa3Rb3Rc3, OR22, OC(O)R23, OCO2R24, OCONR25R26, OP(O)(OR27)2, OSO3R28, N3, phtalimidyl, NR29R30, NR31C(O)R32, NR33C(O)OR34, N(C(O)R35)C(O)R36, N(C(O)R37)C(O)OR38 and N(C(O)OR39)C(O)OR40 group,
R4 represents a hydrogen or halogen atom or an OSiRa4Rb4Rc4, OR41, OC(O)R42, OCO2R43, OCONR44R45, OP(O)(OR46)2 or OSO3R47 group,
or R and R1, together with the carbon atoms carrying them, form a cyclic acetal having the following formula:
and/or (R1 and R2), (R2 and R3), and/or (R3 and R4), together with the carbon atoms carrying them, form a cyclic acetal having the following formula:
and
R5 represents a hydrogen or halogen atom or a R48, OR49 or NR50R51 group, with:
R6 representing:
a hydrogen atom,
a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
a C(O)R52 group, or
a C(O)OR53 group,
R7 representing:
a hydrogen atom,
a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
a C(O)R52 group,
a C(O)OR53 group, or
a N-protecting group,
R8, R15, R22 and R41 representing, independently from one another, a hydrogen atom;
an O-protecting group;
or a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl, (C1-C6)-alkyl-heteroaryl, saccharidic or polysaccharidic group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
R9, R10, R16, R17, R23, R24, R32, R34 to R40, R42, R43, R48, R52 and R53 representing, independently from one another, a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
R11, R12, R18, R19, R25, R26, R29 to R31, R33, R44, R45, R50 and R51 representing, independently from one another, a hydrogen atom or a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among a halogen atom, OH, COOH and CHO,
R13, R14, R20, R21, R27, R28, R46 and R47 representing, independently from one another, a hydrogen atom or a (C1-C6)alkyl group,
R49 representing:
a hydrogen atom,
a (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl, aryl, heteroaryl, aryl-(C1-C6)alkyl, heteroaryl-(C1-C6)alkyl, (C1-C6)-alkyl-aryl or (C1-C6)-alkyl-heteroaryl group, this group being possibly substituted with one or more groups chosen among an halogen atom, OH, COOH and CHO, or
a O-protecting group,
Ra1 to Ra4, Rb1 to Rb4 and Rc1 to Rc4 representing, independently from one another, a (C1-C6)alkyl, aryl or aryl-(C1-C6)alkyl group, and
Rd and Re representing, independently from one another, a hydrogen atom or a (C1-C6)alkyl group.

32 more elements

Facts

Application

13/823,237Filed 22 Dec 2011

Priority

EP 1030649322 Dec 2010

Published

US 2013/0171180 A14 Jul 2013

Granted

3 Nov 2015

Term ends

Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07K 9/001
Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof: the peptide…
A01N 1/126
Preservation or perfusion media: physiologically active agents, e.g. antioxidants or nutrients
A61K 8/64
Containing organic compounds: proteins; Peptides; Derivatives or degradation products thereof
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents