US 6,787,552 B2Granted

PPAR delta activators

AssigneeNippon Chemiphar Co., Ltd.

InventorsShogo Sakuma, Tsuyoshi Endo, Atsushi Tendo, Toshihiro Takahashi, Shinichi Yoshida, Kunio Kobayashi, Nobutaka Mochizuki, Tomio Yamakawa, Takashi Kanda, Seiichiro Masui

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Abstract

Compounds of the general formula (I) or salts thereof and activators of PPARδ (peroxisome proliferator activated receptor δ) containing the compounds or the salts as the active ingredient: wherein R1 and R2 each are hydrogen, C1-8 alkyl, an aryl or heterocyclic group which may be substituted, or the like; A is oxygen, sulfur, or the like; X1 and X2 are each a free valency, oxygen, S(O)p (wherein p is an integer of 0 to 2), C(═O), C(═O)NH, NHC(═O), CH═CH, or the like; Y is optionally substituted C1-8 alkylene; Z is oxygen or sulfur; R3 and R4 are each optionally substituted C1-8 alkyl; and R8 is hydrogen or C1-8 alkyl, with the proviso that when X1 is a free valency, X2 is not O or S(O)p, while when X1 is C(═O)NH, X2 is not a free valency.

Claims34

Dependent claims

A compound having the following general formula (I) or a salt thereof:

wherein R1 is a hydrogen atom, an alkyl group having 1-8 carbon atoms, an alkyl group having 1-8 carbon atoms and a halogen atom substituent, an alkenyl group having 2-8 carbon atoms, an alkynyl group having 2-8 carbon atoms, a 3-7 membered cycloalkyl group, an alkyl group having 1-8 carbon atom and a 3-7 membered substituent, an arylalkyl group that has a C6-10 aryl portion and C1-4 alkyl portion and optionally has a substituent, or an aryl or heterocyclic group which optionally has a substituent;
R2 is a hydrogen atom, an alkyl group having 1-8 carbon atoms, an alkyl group having 1-8 carbon atoms and a halogen atom substituent, an alkenyl group having 2-8 carbon atoms, an alkynyl group having 2-8 carbon atoms, a 3-7 membered cycloalkal group, an alkyl group having 1-8 carbon atom and a 3-7 membered substituent, an arylalkyl group that has a C6-10 aryl portion and C1-4 alkyl portion and optionally has a substituent, or heterocyclic group which optionally has a substituent;
A is O, S, or NR5 in which R5 is H or C1-8, alkyl;
each of X1 and X2 independently is a bond, O, S(O)p in which p is an integer of 0 to 2, C(═O), C(═N—OR6) in which R6 is H or C1-8, alkyl;
C(═O)NH, NHC(═O), SO2NH, NHSO2, CH(OR7) in which R7 is H or C1-8 alkyl, CH═CH, or C≡C;
Y is an alkylene chain having 1-8 carbon atoms and optionally a substituent;
Z is O or S;
each of R3 and R4 independently is an alkyl group having 1-8 carbon atoms and optionally a substituent;
and R8 is a hydrogen atom or an alkyl group having 1-8 carbon atoms;
provided that X2 is neither O nor S(O)p when X1 is a bond, while X2 is not a bond when X1 is C(═O)NH.

7 more elements

An oxazole derivative having the following formula (II) or a salt thereof:

wherein R11 is an alkyl group having 1-8 carbon atoms, an alkyl group having 1-8 carbon atoms and 1-3 halogen atom substituents, an alkenyl group having 2-8 carbon atoms, an alkynyl group having 2-8 carbon atoms, a 3-7 membered cycloalkyl group, an alkyl group having 1-8 carbon atom and a 3-7 membered substituent, or a phenylalkyl group having C1-4 alkyl portion, phenyl group, naphthyl group, pyridyl group, thienyl group, furyl group, quinolyl group, benzofuranyl group or benzothienyl group which optionally contains a substituent of halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkyl having 1-3 halogen substituents, C1-8 alkoxy, C1-8 alkoxy having 1-3 halogen substituents, phenyl, benzyl, phenyloxy, benzoyl or pyridyl;
R12 is an alkal group having 1-8 carbon atoms, an alkyl group having 1-8 carbon atoms and 1-3 halogen atom substituents, an alkenyl group having 2-8 carbon atoms, an alkynyl group having 2-8 carbon atoms, a 3-7 membered cycloalkyl group, an alkyl group having 1-8 carbon atom and a 3-7 membered substituent, or a phenylalkyl group having C1-4 alkyl portion, naphthyl group, pyridyl group, thienyl group, furyl group, quinolyl group, benzofuranyl group or benzothienyl group which optionally contains a substituent of halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkyl having 1-3 halogen substituents, C1-8 alkoxy, C1-8 alkoxy having 1-3 halogen substituents, phenyl, benzyl, phenyloxy, benzoyl or pyridyl;
each of X11 and X12 independently is a bond, S(O)q in which q is an integer of 0 to 2, C(═O), C(═N—OR16) in which R16 is H or C1-8 alkyl;
C(═O)NH, NHC(═O), SO2NH, NHSO2, CH(OR17) in which R17 is H or C1-8 alkyl, CH═CH, or C≡C;
Y1 is an alkylene chain having 1-8 carbon atoms and optionally a C1-8 alkyl or C1-8 alkoxy substituent;
Z1 is O or S;
each of R13 and R14 independently is an alkyl group having 1-8 carbon atoms and optionally a halogen or C1-8 alkoxy substituent;
provided that X12 is neither O nor S (O)q when X11 is a bond, while X12 is not a bond when X11 is C(═O)NH.

5 more elements

A thiazole derivative having the following formula (III) or a salt thereof:

wherein each of R21 and R22 independently is an alkyl group having 1-8 carbon atoms, an alkyl group having 1-8 carbon atoms and 1-3 halogen atom substituents, an alkenyl group having 2-8 carbon atoms, an alkynyl group having 2-8 carbon atoms, a 3-7 membered cycloalkyl group, an alkyl group having 1-8 carbon atom and a 3-7 membered substituent, or a phenylalkyl group having C1-4 alkyl portion, phenyl group, naphthyl group, pyridyl group, thienyl group, furyl group, quinolyl group, benzofliranyl group or benzothienyl group which optionally contains a substituent of halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkyl having 1-3 halogen substituents, C1-8 alkoxy, C1-8 alkoxy having 1-3 halogen substituents, phenyl, benzyl, phenyloxy, benzoyl or pyridyl;
each of X21 and X22 independently is a bond, S(O)r in which r is an integer of 0 to 2, C(═O), C(═N—OR26) in which R26 is H or C1-8 alkyl;
C(═O)NH, NHC(═O), SO2NH, NHSO2, CH(OR27) in which R27 is H or C1-8 alkyl, CH═CH, or C═C;
Y2 is an alkylene chain having 1-8 carbon atoms and optionally a C1-8 alkyl or C1-8 alkoxy substituent;
Z2 is 0 or S;
each of R23 and R24 independently is an alkyl group having 1-8 carbon atoms and optionally a halogen or C1-8 alkoxy substituent;
provided that X22 is neither O nor S(O)r when X21 is a bond, while X22 is not a bond when X21 is C(═O)NH.

4 more elements

An oxazole derivative having the following formula (II) or a salt thereof:

wherein each of R11 and R12 independently is an alkyl group having 1-8 carbon atoms, an alkyl group having 1-8 carbon atoms and 1-3 halogen atom substituents, an alkenyl group having 2-8 carbon atoms, an alkynyl group having 2-8 carbon atoms, a 3-7 membered cycloalkyl group, an alkyl group having 1-8 carbon atom and a 3-7 membered substituent, or a phenylalkyl group having C1-4 alkyl portion, phenyl group, naphthyl group, pyridyl group, thienyl group, furyl group, quinolyl group, benzofuranyl group or benzothienyl group which optionally contains a substituent of halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkyl having 1-3 halogen substituents, C1-8 alkoxy, C1-8 alkoxy having 1-3 halogen substituents, phenyl, benzyl, phenyloxy, benzoyl or pyridyl;
X11 is attached to 4-position of the oxazole ring;
each of X11 and X12 independently is a bond, S(O)q in which q is an integer of 0 to 2, C(═O), C(═N—OR16) in which R16 is H or C1-8 alkyl;
C(═O)NH, NHC(═O), SO2NH, NHSO2, CH(OR17) in which R17 is H or C1-8 alkyl, CH═CH, or C≡C;
Y1 is an alkylene chain having 1-8 carbon atoms and optionally a C1-8 alkyl or C1-8 alkoxy substituent;
Z1 is O or S;
each of R13 and R14 independently is an alkyl group having 1-8 carbon atoms and optionally a halogen or C1-8 alkoxy substituent;
provided that X12 is neither O nor S(O)q when X11 is a bond, while X12 is not a bond when X11 is C(═O)NH.

5 more elements

A thiazole derivative having the following formula (IV) or a salt thereof:

wherein each of R21 and R22 independently is an alkyl group having 1-8 carbon atoms, an alkyl group having 1-8 carbon atoms and 1-3 halogen atom substituents, an alkenyl group having 2-8 carbon atoms, an alkynyl group having 2-8 carbon atoms, a 3-7 membered cycloalkyl group, an alkyl group having 1-8 carbon atoms and a 3-7 membered substituent, or a phenylalkyl group having C1-4 alkyl portion, phenyl group, naphthyl group, pyridyl group, thienyl group, furyl group, quinolyl group, benzofuranyl group or benzothienyl group which optionally contains a substituent of halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkyl having 1-3 halogen substituents, C1-8 alkoxy, C1-8 alkoxy having 1-3 halogen substituents, phenyl, benzyl, phenyloxy, benzoyl or pyridyl;
each of X21 and X22 independently is a bond, S(O)q in which q is an integer of 0 to 2, C(═O), C(═N—OR26) in which R26 is H or C1-8 alkyl;
C(═O)NH, NHC(═O), SO2NH, NHSO2, CH(OR27) in which R27 is H or C1-8 alkyl, CH═CH, or C≡C;
Y2 is an alkylene chain having 1-8 carbon atoms and optionally a C1-8 alkyl or C1-8 alkoxy substituent;
each of R23 and R24 independently is an alkyl group having 1-8 carbon atoms and optionally a halogen or C1-8 alkoxy substituent;
provided that X22 is neither O nor S(O)q when X21 is a bond, while X22 is not a bond when X21 is C(═O)NH.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/344,496Filed 11 Feb 2003
Priority: JP 2000-24359611 Aug 2000
Published: US 2004/0097739 A120 May 2004
Granted: 7 Sep 2004
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 413/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics