US 8,796,320 B2Granted

1,3,4-Oxadiazole-2-carboxamide compound

AssigneesGeneral Incorporated Association Pharma Valley Project Supporting Organization, Pharma Design, Inc., Shizuoka Prefecture, Kumamoto Health Science University, Kabushiki Kaisha Yakult Honsha

InventorsAkira Asai, Kenji Matsuno, Naohisa Ogo, Osamu Takahashi, Yoshiaki Masuda, Ayumu Muroya, Yasuto Akiyama, Tadashi Ashizawa, Tadashi Okawara

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Abstract

Provided is a 1,3,4-oxadiazole-2-carboxamide compound which has STAT3 inhibitory activity and is useful as an anticancer agent. Provided is a 1,3,4-oxadiazole-2-carboxamide compound represented by formula (I) or a pharmacologically acceptable salt thereof (in the formula, Ar represents a furyl group or the like; R1 represents a hydrogen atom or the like; and —X—Y represents a diaryl group such as a biphenyl group).

Claims20

Dependent claims

A 1,3,4-oxadiazole-2-carboxamide compound of formula (Ia) or a pharmaceutically acceptable salt thereof:

wherein
each R3 is the same or different and is
i) a hydrogen atom,
ii) a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, aromatic heterocyclic alkyl group,
iii) COR11, wherein R11 is a hydrogen atom, or a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, or aromatic heterocyclic alkyl group,
iv) COOR12, wherein R12 is as defined in R11,
v) C(═Q1)NR13R14,wherein Q1 is an oxygen atom, a sulfur atom, or NR15 (wherein R15 is as defined in R11);
and R13 and R14 are the same or different and are a hydrogen atom, a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, or aromatic heterocyclic alkyl group;
or a group formed by linking R13 and R14 together, which is a nitrogen-comprising heterocyclic group,
vi) OR16, wherein R16 is as defined in R11,
vii) OCOR17, wherein R17 is as defined in R11,
viii) S(O)pR18, wherein p is an integer of 0 to 3, and R18 is as defined in R11
ix) SO2NR19R20, wherein R19 and R20 are the same or different and are as defined in R13 and R14, respectively,
x) NR21R22 wherein R21 and R22 are the same or different and are each a hydrogen atom, a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, aromatic heterocyclic alkyl group, COR23 (wherein R23 is as defined in R11), COOR24 (wherein R24 is as defined in R11), or SO2R25 (wherein R25 is as defined in R11) or a group formed by linking R21 and R22 together, which is a nitrogen-comprising heterocyclic group,
xi) N(R26)C(═Q2)NR27R28, wherein, Q2 represents an oxygen atom, a sulfur atom, or NR29 (wherein R29 is as defined in R11), NCN, CHNO2, or C(CN)2;
R26 is as defined in R11;
and R27 and R28 are the same or different and are as in R13 and R14, respectively,
xii) N(R30)SO2NR31R32, wherein R30 is as defined in R11;
and R31 and R32 are the same or different and are as defined in R13 and R14, respectively,
xiii) SiR33R34R35, wherein R33, R34, and R35 are the same or different and are each as defined in R11,
xiv) a nitro group,
xv) a cyano group,
xvi) a halogen atom, or
xvii) a pentahalogenothio group;
n is an integer of 0 to 2;
Z3 is —CH═ or —N═;
Y is an aryl, aromatic heterocyclic, or dioxaborolanyl group which optionally comprises one to three substituents selected from the group consisting of:
i) a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group,
ii) COR41, wherein R41 is as defined in R11,
iii) COOR42, wherein R42 is as defined in R11,
iv) C(═Q3)NR43R44, wherein Q3 is as defined in Q1, and R43 and R44 are the same or different and are as defined in R13 and R14, respectively,
v) OR45, wherein R45 is as defined in R11,
vi) OCOR46, wherein R46 is as defined in R11,
vii) S(O)qR47, wherein q is an integer of 0 to 3, and R47 is as defined in R11,
viii) SO2NR48R49, wherein R48 and R49 are the same or different and are as defined in R13 and R14, respectively,
ix) NR50R51, wherein R50 and R51 are the same or different and are as defined in R21 and R22, respectively,
x) N(R52)C(═Q4)NR53R54, wherein Q4 is as defined in Q2 R52 is as defined in R11, and R53 and R54 are the same or different and are as defined in R13 and R14, respectively,
xi) N(R55)SO2NR56R57, wherein R55 is as defined in R11, and R56 and R57 are the same or different and are as defined in R13 and R14, respectively,
xii) SiR58 R59R60, wherein R58, R59, and R60 are the same or different and are each as defined in R11,
xiii) a nitro group,
xiv) a cyano group, and
xv) a halogen atom.

39 more elements

A 1,3,4-oxadiazole-2-carboxamide compound of formula (Ib) or a pharmaceutically acceptable salt thereof:

wherein
each R3 is the same or different and is
i) a hydrogen atom,
ii) a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, aromatic heterocyclic alkyl group,
iii) COR11, wherein R11 is a hydrogen atom, or a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, or aromatic heterocyclic alkyl group,
iv) COOR12, wherein R12 is as defined in R11,
v) C(═Q1)NR13R14, wherein Q1 is an oxygen atom, a sulfur atom, or NR15 (wherein R15 is as defined in R11);
and R13 and R14 are the same or different and are a hydrogen atom, a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, or aromatic heterocyclic alkyl group;
or a group formed by linking R13 and R14 together, which is a nitrogen-comprising heterocyclic group,
vi) OR16, wherein R16 is as defined in R11,
vii) OCOR17, wherein R17 is as defined in R11,
viii) S(O)pR18, wherein p is an integer of 0 to 3, and R18 is as defined in R11 ,
ix) SO2NR19R20, wherein R19 and R20 are the same or different and are as defined in R13 and R14, respectively,
x) NR21R22,wherein R21 and R22 are the same or different and are each a hydrogen atom, a substituted or unsubstituted alkyl group cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, aromatic heterocyclic alkyl group, COR23 (wherein R23 is as defined in R11), COOR24 (wherein R24 is as defined in R11), or SO2R25 (wherein R25 is as defined in R11);
or a group formed by linking R21 and R22 together, which is a nitrogen-comprising heterocyclic group,
xi) N(R26)C(═Q2)NR27R28, wherein, Q2 represents an oxygen atom, a sulfur atom, or NR29 (wherein R29 is as defined in R11), NCN, CHNO2 or C(CN)2;
R26 is as defined in R11;
and R27 and R28 are the same or different and are as in R13 and R14, respectively,
xii) N(R30)SO2NR31R32, wherein R30 is as defined in R11;
and R31 and R32 are the same or different and are as defined in R13 and R14, respectively,
xiii) SiR33R34R35, wherein R33, R34, and R35 are the same or different and are each as defined in R11,
xiv) a nitro group,
xv) a cyano group,
xvi) a halogen atom, or
xvii) a pentahalogenothio group;
n is an integer of 0 to 2;
Z3 and Z5 are the same or different and are —CH═ or —N═;
one of Z4 and Z6 is —O—or —S—, and the other is —CH═ or —N═;
Y is an aryl, aromatic heterocyclic, or dioxaborolanyl group which optionally comprises one to three substituents selected from the group consisting of:
i) a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group,
ii) COR41, wherein R41 is as defined in R11,
iii) COOR42, wherein R42 is as defined in R11,
iv) C(═Q3)NR43R44 wherein Q3 is as defined in Q1, and R43 and R44 are the same or different and are as defined in R13 and R14, respectively,
v) OR45, wherein R45 is as defined in R11,
vi) OCOR46, wherein R46 is as defined in R11,
vii) S(O)qR47, wherein q is an integer of 0 to 3, and R47 is as defined in R11,
viii) SO2NR48R49, wherein R48 and R49 are the same or different and are as defined in R13 and R14, respectively,
ix) NR50R51, wherein R50 and R51 are the same or different and are as defined in R21 and R22, respectively,
x) N(R52)C(═Q4)NR53R54, wherein Q4 is as defined in Q2R52 is as defined in R11, and R53 and R54 are the same or different and are as defined in R13 and R14, respectively,
xi) N(R55)SO2NR56R57, wherein R55 is as defined in R11 , and R56 and R57 are the same or different and are as defined in R13 and R14, respectively,
xii) SiR58R59R60, wherein R58, R59, and R60 are the same or different and are each as defined in R11,
xiii) a nitro group,
xiv) a cyano group, and
xv) a halogen atom.

41 more elements

A 1,3,4-oxadiazole-2-carboxamide compound of formula (Ic) or a pharmaceutically acceptable salt thereof:

wherein
each R3 is the same or different and is
i) a hydrogen atom,
ii) a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, aromatic heterocyclic alkyl group,
iii) COR11, wherein R11 is a hydrogen atom, or a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, or aromatic heterocyclic alkyl group,
iv) COOR12, wherein R12 is as defined in R11,
v) C(═Q1)NR13R14, wherein Q1 is an oxygen atom, a sulfur atom, or NR15 (wherein R15 is as defined in R11);
and R13 and R14 are the same or different and are a hydrogen atom a substituted or unsubstituted alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, or aromatic heterocyclic alkyl or a group;
formed by linking R13 and R14 together, which is a nitrogen-comprising heterocyclic group,
vi) OR16, wherein R16 is as defined in R11,
vii) OCOR17, wherein R17 is as defined in R11,
viii) S(O)pR18, wherein p is an integer of 0 to 3, and R11is as defined in R11,
ix) SO2NR19R20, wherein R19 and R20 are the same or different and are as defined in R13 and R14, respectively,
x) NR21R22, wherein R21 and R22 are the same or different and are each a hydrogen atom, a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, aromatic heterocyclic alkyl group, COR23 (wherein R23 is as defined in R11, COOR24 (wherein R24 is as defined in R11), or SO2R25 (wherein R25 is as defined in R11);
or a group formed by linking R21 and R22 together, which is a nitrogen-comprising heterocyclic group,
xi) N(R26)C(═Q2)NR27R28, wherein, Q2 represents an oxygen atom, a sulfur atom, or NR29 (wherein R29 is as defined in R11), NCN, CHNO2or C(CN)2;
R26 is as defined in R11;
and R27 and R28 are the same or different and are as in R13 and R14, respectively,
xii) N(R30)SO2NR31R32,wherein R30 is as defined in R11;
and R31 and R32 are the same or different and are as defined in R13 and R14, respectively,
SiR33R34R35, wherein R33, R34, and R35 are the same or different and are each as defined in R11,
xiv) a nitro group,
xv a c group,
xvi) a halogen atom, or
xvii) a pentahalogenothio group;
n is an integer of 0 to 2;
Z7 and Z8 are the same or different and are —CH═ or —N═;
Z9 is —O—, —S—, or —N(R4)—, wherein R4 is a hydrogen atom, a substituted or unsubstituted alkyl group, or may form a ring together with an adjacent carbon atom through —(CH2)r—(wherein r is an integer of 3 to 6);
Y is an aryl, aromatic heterocyclic, or dioxaborolanyl group which optionally comprises one to three substituents selected from the group consisting of:
i) a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group,
ii) COR41, wherein R41 is as defined in R11,
iii) COOR42, wherein R42 is as defined in R11,
iv) C(═Q3)NR43R44, wherein Q3 is as defined in Q1, and R43 and R44 are the same or different and are as defined in R13 and R14, respectively,
v) OR45, wherein R45 is as defined in R11,
vi) OCOR46, wherein R46 is as defined in R11,
vii) S(O)qR47, wherein q is an integer of 0 to 3, and R47 is as defined in R11,
viii) SO2NR48 R49, wherein R48 and R49 are the same or different and are as defined in R13 and R14, respectively,
ix) NR50R51, wherein R50 and R51 are the same or different and are as defined in R21 and R22, respectively,
x) N(R52)C(═Q4)NR53R54, wherein Q4 is as defined in Q2 R52 is as defined in R11, R53 and R54 are the same or different and are as defined in R13 and R14, respectively,
xi) N(R55)SO2NR56R57, wherein R55 is as defined in R11, and R56 and R57 are the same or different and are as defined in R13 and R14, respectively,
xii) SiR58R59R60, wherein R58, R59, and R60 are the same or different and are each as defined in R11,
xiii) a nitro group,
xiv) a cyano group, and
xv) a halogen atom.

41 more elements

A 1,3,4-oxadiazole-2-carboxamide compound selected from the group consisting of:

N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-1);
N-[5(2-furyl)-1,3,4-oxadiazol-2-yl]-2′-hydroxy-3-biphenyl carboxamide (Compound Ia-2);
2′-formyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-3);
N-[5-(2-furyl)- 1,3,4-oxadiazol-2-yl]-3′-hydroxy-3-biphenylcarboxamide (Compound Ia-4);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3′-nitro-3-biphenylcarboxamide (Compound Ia-5);
3′-formyl-N[5-(2-furyl)- 1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-6);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3′-methoxycarbonyl-3-biphenylcarboxamide (Compound Ia-7);
3′-carboxy-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-8);
3′-cyano-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-9);
4′-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-10);
4′-chloro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-11);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-methyl-3-biphenylcarboxamide (Compound Ia-12);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-vinyl-3-biphenylcarboxamide (Compound Ia-13);
4′-tert-butyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-14);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-hydroxy-3-biphenylcarboxamide (Compound Ia-15);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-methoxy-3-biphenylcarboxamide (Compound Ia-16);
4′-formyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-17);
4′-acetyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-18);
4′-benzoyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-19);
4′-carbamoyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-20);
4′-cyano-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-21);
4′-cyanomethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-22);
4′-n-butoxycarbonyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-23);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-nitro-3-biphenylcarboxamide (Compound Ia-24);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-sulfamoyl-3-biphenylcarboxamide (Compound Ia-25);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(N-methylsulfamoyl)-3-biphenylcarboxamide (Compound Ia-26);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(N,N-dimethylsulfamoyl)-3-biphenylcarboxamide (Compound Ia-27);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-methanesulfonyl-3-biphenylcarboxamide (Compound Ia-28);
4′-cyano-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-240 -methyl-3-biphenylcarboxamide (Compound Ia-29);
4′-acetyl-3′-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-30);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-sulfamoyl-4-biphenylcarboxamide (Compound Ia-31);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1-naphthyl)benzenecarboxamide (Compound Ia-32);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(2-naphthyl) benzenecarboxamide (Compound Ia-33);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(5-methyl-2-furyl)benzenecarboxamide (Compound Ia-34);
3-(2-cyano-5-pyridyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-35);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(5-sulfamoyl-2-thienyl)benzenecarboxamide (Compound Ia-36);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(3-pyridyl)benzenecarboxamide trifluoroacetate (Compound Ia-37);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(2-hydroxy-5-pyridyl)benzenecarboxamide (Compound Ia-38);
3-(2-amino-5-pyridyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-39);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(2-methylthio-5-pyridyl)benzenecarboxamide (Compound Ia-40);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(4-pyridyl)benzenecarboxamide (Compound Ia-41);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(3,4-methylenedioxyphenyl)-benzenecarboxamide (Compound Ia-42);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1-methyl-6-indolyl)benzenecarboxamide (Compound Ia-43);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1-methyl-5-indolinyl)benzenecarboxamide (Compound Ia-44);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1-methyl-5-indazolyl)benzenecarboxamide (Compound Ia-45);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1-methyl-6-benzimidazolyl)-benzenecarboxamide (Compound Ia-46);
3-(5-benzothienyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-47);
3-(5-benzothiazolyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-48);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-[9-methyl-3-(9H-carbazolyl)]benzenecarboxamide (Compound Ia-49);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1-methyl-5-indolyl)benzenecarboxamide (Compound Ia-50);
2-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1-methyl-5-indolyl)benzenecarboxamide (Compound Ia-51);
5-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1-methyl-5-indolyl)benzenecarboxamide (Compound Ia-52);
2-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(1-methyl-5-indolyl)benzenecarboxamide (Compound Ia-53);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-phenyl-4-pyridinecarboxamide (Compound Ia-54);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2,6-diphenyl-4-pyridinecarboxamide (Compound Ia-55);
2-(4-bromophenyl)-6-(4-chlorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4-pyridinecarboxamide (Compound Ia-56);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-phenyl-5-pyridinecarboxamide (Compound Ia-57);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(1-methyl-5-indolyl)-3-pyridinecarboxamide (Compound Ia-58);
4′-cyano-3′-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-59);
4′-(2-cyano-2-propyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-60);
4′-tert-butyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-31-nitro-3-biphenylcarboxamide (Compound Ia-61);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-trimethylsilyl-3-biphenylcarboxamide (Compound Ia-62);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-trifluoromethyl-3-biphenylcarboxamide (Compound Ia-63);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-trifluoromethoxy-3-biphenylcarboxamide (Compound Ia-64);
4′-benzyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-65);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-phenoxy-3-biphenylcarboxamide (Compound Ia-66);
4′-diphenylamino-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-67);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-ureido-3-biphenylcarboxamide (Compound Ia-68);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-methoxycarbonyl-3-biphenylcarboxamide (Compound Ia-69);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-propionyl-3-biphenylcarboxamide (Compound Ia-70);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-piperidinosulfonyl-3-biphenylcarboxamide (Compound Ia-71);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-sulfo-3-biphenylcarboxamide (Compound Ia-72);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(o-terphenyl)carboxamide (Compound Ia-73);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(m-terphenyl)carboxamide (Compound Ia-74);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-75);
3′-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-76);
4″-chloro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-77);
4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-78);
4″-ethoxy-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-79);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-propoxy-3-(p-terphenyl)carboxamide (Compound Ia-80);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-isopropoxy-3-(p-terphenyl)carboxamide (Compound Ia-81);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(1-naphthyl)-3-biphenylcarboxamide (Compound Ia-82);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(2-naphthyl)-3-biphenylcarboxamide (Compound Ia-83);
4′-cyclohexyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-84);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(trans-4-n-propylcyclohexyl)-3-biphenylcarboxamide (Compound Ia-85);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3′-morpholino-3-biphenylcarboxamide (Compound 1a-86);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-morpholino-3-biphenylcarboxamide (Compound Ia-87);
4′-(4-tert-butoxycarbonyl-1-piperazinyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-88);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(1-piperazinyl)-3-biphenylcarboxamide (Compound Ia-89);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(2-morpholinoethyl)-3-biphenylcarboxamide (Compound Ia-90);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(2-pyridyl)benzenecarboxamide (Compound Ia-91);
3-(2-cyano-5-pyridyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-92);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(2-trifluoromethyl-5-pyridyl)benzenecarboxamide (Compound Ia-93);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(2-morpholino-3-pyridyl)benzenecarboxamide (Compound Ia-94);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(2-morpholino-4-pyridyl)benzenecarboxamide (Compound Ia-95);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-[2-(1-piperazinyl)-5-pyridyl)benzenecarboxamide (Compound Ia-96);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(5-phenyl-2-thienyl)benzenecarboxamide (Compound Ia-97);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(2-morpholino-5-pyrimidinyl)benzenecarboxamide (Compound Ia-98);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(3-quinolyl)benzenecarboxamide (Compound Ia-99);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(6-quinoxalinyl)benzenecarboxamide (Compound Ia-100);
3-(5-benzofurazanyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-101);
3-(3,4-ethylenedioxyphenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-102);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(4-methyl-1-naphthyl)benzenecarboxamide (Compound Ia-103);
3-(2-ethoxy-1-naphthyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-104);
3-(4-fluoro-1-naphthyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-105);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(3-methoxy-2-naphthyl)benzenecarboxamide (Compound Ia-106);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(6-methoxy-2-naphthyl)benzenecarboxamide (Compound Ia-107);
3-(6-ethoxy-2-naphthyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-108);
3-(6-benzyloxy-2-naphthyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-109);
3-(9-anthryl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-110);
3-(5-acenaphthenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]benzenecarboxamide (Compound Ia-111);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)benzenecarboxamide (Compound Ia-112);
4″-ethyl-2-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-113);
4″-ethyl-4-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-114);
4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4-methyl-3-(p-terphenyl)carboxamide (Compound Ia-115);
4″-ethyl-5-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-116);
6-(4-biphenylyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-pyridinecarboxamide (Compound Ia-117);
6-(4′-ethyl-4-biphenylyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-pyridinecarboxamide (Compound Ia-118);
5-(4-biphenylyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-pyridinecarboxamide (Compound Ia-119);
5-(4′-ethyl-4-biphenylyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-pyridinecarboxamide (Compound Ia-120);
4′-bromo-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]1-3-biphenylcarboxamide (Compound Ia-121);
2″-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-122);
2″-chloro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-123);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2″-methyl-3-(p-terphenyl)carboxamide (Compound Ia-124);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2″-methoxy-3-(p-terphenyl)carboxamide (Compound Ia-125);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2″-trifluoromethyl-3-(p-terphenyl)carboxamide (Compound Ia-126);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2″-trifluoromethoxy-3-(p-terphenyl)carboxamide (Compound Ia-127);
2″-cyano-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-128);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1,1′:4′,1″:2″,1′″-quaterphenyl)carboxamide (Compound Ia-129);
3″-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-130);
3″-chloro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-131);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3″-methyl-3-(p-terphenyl)carboxamide (Compound Ia-132);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3″-methoxy-3-(p-terphenyl)carboxamide (Compound Ia-133);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3″-trifluoromethyl-3-(p-terphenyl)carboxamide (Compound Ia-134);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3″-trifluoromethoxy-3-(p-terphenyl)carboxamide (Compound Ia-135);
3″-cyano-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-136);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]3-(1,1′:4′,1″:3″,1′″-quaterphenyl)carboxamide (Compound Ia-137);
4″-fluoro-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-138);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-methyl-3-(p-terphenyl)carboxamide (Compound Ia-139);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-methoxy-3-(p-terphenyl)carboxamide (Compound Ia-140);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-trifluoromethyl-3-(p-terphenyl)carboxamide (Compound Ia-141);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]1-4″-trifluoromethoxy-3-(p-terphenyl)carboxamide (Compound Ia-142);
4″-cyano-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-143);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(1,1′:4′,1″4″,1′″-quaterphenyl)carboxamide (Compound Ia-144);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-trimethylsilyl-3-(p-terphenyl)carboxamide (Compound Ia-145);
4′-(1-cyclohexenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-146);
4′-(4,4-dimethyl-1-cyclohexenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-147);
4′-(4-tert-butyl-1-cyclohexenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-148);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(2,2,6,6-tetramethyl-3,6-dihydro-4-pyranyl)-3-biphenylcarboxamide (Compound Ia-149);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(1-methyl -1,2,3,6-tetrahydro-4-pyridyl)-3-biphenylcarboxamide (Compound Ia-150);
4′-(2-furyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-biphenylcarboxamide (Compound Ia-151);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(2-thienyl)-3-biphenylcarboxamide (Compound Ia-152);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(3-thienyl)-3-biphenylcarboxamide (Compound Ia-153);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(1-methyl-4-pyrazolyl)-3-biphenylcarboxamide (Compound Ia-154);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(4-pyridyl)-3-biphenylcarboxamide (Compound Ia-155);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4′-(1-methyl-5-indolyl)-3-biphenylcarboxamide (Compound Ia-156);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3″-hydroxy-3-(p-terphenyl)carboxamide (Compound Ia-157);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-(1-propyl)-3-(p-terphenyl)carboxamide (Compound Ia-158);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-isopropyl-3-(p-terphenyl)carboxamide (Compound Ia-159);
4″-(1-butyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-160);
4″-tert-butyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-161);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-hydroxy-3-(p-terphenyl)carboxamide (Compound Ia-162);
4″-(N,N-dimethylamino)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-163);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-methanesulfonyl-3-(p-terphenyl)carboxamide (Compound Ia-164);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-4″-sulfamoyl-3-(p-terphenyl)carboxamide (Compound Ia-165);
5-chloro-4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-166);
4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-nitro-3-(p-terphenyl)carboxamide (Compound Ia-167);
5-acetylamino-4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-168);
4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-trifluoromethyl-3-(p-terphenyl)carboxamide (Compound Ia-169);
4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-trifluoromethoxy-3-(p-terphenyl)carboxamide (Compound Ia-170);
5-cyano-4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-(p-terphenyl)carboxamide (Compound Ia-171);
4″-ethyl-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-pentafluorothio-3-(p-terphenyl)carboxamide (Compound Ia-172);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-1);
5-(3-chlorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-2);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(4-methylphenyl)-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-3);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(3,4-dimethoxyphenyl)-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-4);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-methyl-6-phenyl-4-benzo[d]isoxazolecarboxamide (Compound Ib-5);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(2-naphthyl)-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-6);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-(4-methylpiperidino)-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-7);
5-phenyl-N-(5-phenyl-1,3,4-oxadiazol-2-yl)-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-8);
N-[5-(2-chlorophenyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-9);
N-[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-10);
N-[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-11);
N-[5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-12);
N-(5-benzyl-1,3,4-oxadiazol-2-yl)-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-13);
N-[5-(2-methyl-3-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-14);
N-[5-(2,5-dimethyl-3-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-15);
5-phenyl-2-piperidino-N-[5-(2-thienyl)-1,3,4-oxadiazol-2-yl]-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-16);
N-[5-(3-methyl-2-thienyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-17);
N-[5-(5-methyl-2-thienyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-18);
5-phenyl-2-piperidino-N-[5-(3-thienyl)-1,3,4-oxadiazol-2-yl]-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-19);
N-[5-(5-isoxazolyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridineearboxamide (Compound Ib-20);
N-[5-(1-methyl-3-pyrazolyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-21);
N-[5-(2,4-dimethyl-5-thiazolyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-22);
N-[5-(3-pyridyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-23);
N-{5-[(2,3-dihydrobenzo[1,4]dioxinyl)]-1,3,4-oxadiazol-2-yl}-5-phenyl-2-piperidino-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-24);
5-phenyl-2-piperidino-N-{5-[2-(4,5,6,7-tetrahydrobenzothienyl)]-1,3 ,4-oxadiazol-2-yl}-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-25);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-(1-pyrrolidinyl)-5-(2-thienyl)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-26);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-piperidino-5-(2-thienyl)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-27);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-morpholino-5-(2-thienyl)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-28);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-(1-pyrrolidinyl)-5-(3-pyridyl)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-29);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-(4-thiomorpholinyl)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-30);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-(1-methyl-4-piperazinyl)-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-31);
2-(4,4-difluoropiperidino)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-32);
(dl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-(2-methylpiperidino)-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-33);
(dl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-(3-trifluoromethylpiperidino)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-34);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-(4-trifluoromethylpiperidino)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-35);
2-(4-cyanopiperidino)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-36);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-morpholino-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-37);
2-(1-azetidinyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]1-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound lb-38);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-(1-pyrrolidinyl)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-39);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-(1,2,3,4-tetrahydro-l-quinolyl)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-40);
2-acetylamino-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-41);
2-tert-butoxycarbonylamino-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-42);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-(N-methylanilino)-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-43);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-(4-hydroxypiperidino)-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-44);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-(4-phenylpiperidino)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-45);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-(4-piperidinopiperidino)-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-46);
2-(2,2-dimethylmorpholino)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-47);
(dl)-2-[2(2-azabicyclo[2.2.1]heptyl]-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-48);
2-[N-methyl-N-(3,3,3-trifluoro-l-propypamino]-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-49);
2-(N,N-dimethylamino)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-50);
2-amino-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-7-thiazolo[4,5-b]pyridinecarboxamide (Compound Ib-51);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-furancarboxamide (Compound Ic-1);
5-(2-fluorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-2);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(2-nitrophenyl)-2-furancarboxamide (Compound Ic-3);
5-(3-chlorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-4);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(3-nitrophenyl)-2-furancarboxamide (Compound Ic-5);
5-(4-fluorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]1-2-furancarboxamide (Compound Ic-6);
5-(4-chlorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-7);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(4-methoxyphenyl)-2-furancarboxamide (Compound Ic-8);
5-(4-aminophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-9);
5-(4-acetylaminophenye-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-10);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(4-nitrophenyl)-2-furancarboxamide (Compound Ic-11);
5-(4-ethoxycarbonylphenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-12);
5-(2,4-dichlorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-13);
5-(2-chloro-4-nitrophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-14);
5-(4-amino-2-methylphenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-15);
5-(4-acetylamino-2-methylphenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-16);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(2-methyl-4-nitrophenyl)-2-furancarboxamide (Compound Ic-17);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-(2-methoxy-4-nitrophenyl)-2-furancarboxamide (Compound Ic-18);
5-(2-chloro-5-nitrophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-19);
5-(4-chloro-3-nitrophenye-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-20);
5-(3,5-dichlorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-21);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-methyl-5-phenyl-3-furancarboxamide (Compound Ic-22);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-phenyl-2-thiophenecarboxamide (Compound Ic-23);
5-(4-cyanophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-thiophenecarboxamide (Compound Ic-24);
N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-3-phenyl-1-(6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepinecarboxamide (Compound Ic-25);
3-(4-fluorophenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-1-(6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepinecarboxamide (Compound Ic-26);
4-(4-biphenylyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-thiophenecarboxamide (Compound Ic-27);
4-(4′-ethyl-4-biphenylyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-thiophenecarboxamide (Compound Ic-28);
and
5-(4-carboxyphenyl)-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-2-furancarboxamide (Compound Ic-29),
or a pharmaceutically acceptable salt thereof.

251 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/519,707Filed 28 Dec 2010
Priority: JP 2009-29796028 Dec 2009
Published: US 2012/0302524 A129 Nov 2012
Granted: 5 Aug 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 413/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07D 413/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms:…

Family

US 2012/0302524 A1Pre-grant publication · published 29 Nov 2012
US 8,796,320 B2This patent

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

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1,3,4-Oxadiazole-2-carboxamide compound

AssigneesGeneral Incorporated Association Pharma Valley Project Supporting Organization, Pharma Design, Inc., Shizuoka Prefecture, Kumamoto Health Science University, Kabushiki Kaisha Yakult Honsha

InventorsAkira Asai, Kenji Matsuno, Naohisa Ogo, Osamu Takahashi, Yoshiaki Masuda, Ayumu Muroya, Yasuto Akiyama, Tadashi Ashizawa, Tadashi Okawara

Life of this patent

Estimating the term…

Abstract

A 1,3,4-oxadiazole-2-carboxamide compound of formula (Ia) or a pharmaceutically acceptable salt thereof:

wherein
each R3 is the same or different and is
i) a hydrogen atom,
ii) a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, aromatic heterocyclic alkyl group,
iii) COR11, wherein R11 is a hydrogen atom, or a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, or aromatic heterocyclic alkyl group,
iv) COOR12, wherein R12 is as defined in R11,
v) C(═Q1)NR13R14,wherein Q1 is an oxygen atom, a sulfur atom, or NR15 (wherein R15 is as defined in R11);
and R13 and R14 are the same or different and are a hydrogen atom, a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, or aromatic heterocyclic alkyl group;
or a group formed by linking R13 and R14 together, which is a nitrogen-comprising heterocyclic group,
vi) OR16, wherein R16 is as defined in R11,
vii) OCOR17, wherein R17 is as defined in R11,
viii) S(O)pR18, wherein p is an integer of 0 to 3, and R18 is as defined in R11
ix) SO2NR19R20, wherein R19 and R20 are the same or different and are as defined in R13 and R14, respectively,
x) NR21R22 wherein R21 and R22 are the same or different and are each a hydrogen atom, a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group, aryl group, aralkyl group, aromatic heterocyclic group, aromatic heterocyclic alkyl group, COR23 (wherein R23 is as defined in R11), COOR24 (wherein R24 is as defined in R11), or SO2R25 (wherein R25 is as defined in R11) or a group formed by linking R21 and R22 together, which is a nitrogen-comprising heterocyclic group,
xi) N(R26)C(═Q2)NR27R28, wherein, Q2 represents an oxygen atom, a sulfur atom, or NR29 (wherein R29 is as defined in R11), NCN, CHNO2, or C(CN)2;
R26 is as defined in R11;
and R27 and R28 are the same or different and are as in R13 and R14, respectively,
xii) N(R30)SO2NR31R32, wherein R30 is as defined in R11;
and R31 and R32 are the same or different and are as defined in R13 and R14, respectively,
xiii) SiR33R34R35, wherein R33, R34, and R35 are the same or different and are each as defined in R11,
xiv) a nitro group,
xv) a cyano group,
xvi) a halogen atom, or
xvii) a pentahalogenothio group;
n is an integer of 0 to 2;
Z3 is —CH═ or —N═;
Y is an aryl, aromatic heterocyclic, or dioxaborolanyl group which optionally comprises one to three substituents selected from the group consisting of:
i) a substituted or unsubstituted alkyl group, cycloalkyl group, alkenyl group, alkynyl group, alicyclic heterocyclic group, alicyclic heterocyclic alkyl group,
ii) COR41, wherein R41 is as defined in R11,
iii) COOR42, wherein R42 is as defined in R11,
iv) C(═Q3)NR43R44, wherein Q3 is as defined in Q1, and R43 and R44 are the same or different and are as defined in R13 and R14, respectively,
v) OR45, wherein R45 is as defined in R11,
vi) OCOR46, wherein R46 is as defined in R11,
vii) S(O)qR47, wherein q is an integer of 0 to 3, and R47 is as defined in R11,
viii) SO2NR48R49, wherein R48 and R49 are the same or different and are as defined in R13 and R14, respectively,
ix) NR50R51, wherein R50 and R51 are the same or different and are as defined in R21 and R22, respectively,
x) N(R52)C(═Q4)NR53R54, wherein Q4 is as defined in Q2 R52 is as defined in R11, and R53 and R54 are the same or different and are as defined in R13 and R14, respectively,
xi) N(R55)SO2NR56R57, wherein R55 is as defined in R11, and R56 and R57 are the same or different and are as defined in R13 and R14, respectively,
xii) SiR58 R59R60, wherein R58, R59, and R60 are the same or different and are each as defined in R11,
xiii) a nitro group,
xiv) a cyano group, and
xv) a halogen atom.

39 more elements

Facts

Application

13/519,707Filed 28 Dec 2010

Priority

JP 2009-29796028 Dec 2009

Published

US 2012/0302524 A129 Nov 2012

Granted

5 Aug 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 413/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07D 413/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms:…