IP Library Granted Patent US 8,796,320
Granted Patent B2
US 8,796,320 · App. 13/519,707 · Granted Aug 5, 2014

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

Inventors: Akira Asai (Shizuoka, JP); Kenji Matsuno (Okayama, JP); Naohisa Ogo (Shizuoka, JP); Osamu Takahashi (Chuo-ku, JP); Yoshiaki Masuda (Chuo-ku, JP); Ayumu Muroya (Chuo-ku, JP); Yasuto Akiyama (Sunto-gun, JP); Tadashi Ashizawa (Sunto-gun, JP); Tadashi Okawara (Kumamoto, JP)
Assignees: General Incorporated Association Pharma Valley Project Supporting Organization; Pharma Design; Shizuoka Prefecture; Kumamoto Health Science University; Kabushiki Kaisha Yakult Honsha
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Quick Facts
Patent No.
US 8,796,320
App. No.
13/519,707
Granted
Aug 5, 2014
Kind
B2
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; R 1 represents a hydrogen atom or the like; and —X—Y represents a diaryl group such as a biphenyl group).

Claims (402)

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

wherein

each R 3 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) COR 11 , wherein R 11 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) COOR 12 , wherein R 12 is as defined in R 11 ,

v) C(═Q 1 )NR 13 R 14 ,wherein Q 1 is an oxygen atom, a sulfur atom, or NR 15 (wherein R 15 is as defined in R 11 ); and R 13 and R 14 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 R 13 and R 14 together, which is a nitrogen-comprising heterocyclic group,

vi) OR 16 , wherein R 16 is as defined in R 11 ,

vii) OCOR 17 , wherein R 17 is as defined in R 11 ,

viii) S(O)pR 18 , wherein p is an integer of 0 to 3, and R 18 is as defined in R 11

ix) SO 2 NR 19 R 20 , wherein R 19 and R 20 are the same or different and are as defined in R 13 and R 14 , respectively,

x) NR 21 R 22 wherein R 21 and R 22 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, COR 23 (wherein R 23 is as defined in R 11 ), COOR 24 (wherein R 24 is as defined in R 11 ), or SO 2 R 25 (wherein R 25 is as defined in R 11 ) or a group formed by linking R 21 and R 22 together, which is a nitrogen-comprising heterocyclic group,

xi) N(R 26 )C(═Q 2 )NR 27 R 28 , wherein, Q 2 represents an oxygen atom, a sulfur atom, or NR 29 (wherein R 29 is as defined in R 11 ), NCN, CHNO 2 , or C(CN) 2 ; R 26 is as defined in R 11 ; and R 27 and R 28 are the same or different and are as in R 13 and R 14 , respectively,

xii) N(R 30 )SO 2 NR 31 R 32 , wherein R 30 is as defined in R 11 ; and R 31 and R 32 are the same or different and are as defined in R 13 and R 14 , respectively,

xiii) SiR 33 R 34 R 35 , wherein R 33 , R 34 , and R 35 are the same or different and are each as defined in R 11 ,

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;

Z 3 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) COR 41 , wherein R 41 is as defined in R 11 ,

iii) COOR 42 , wherein R 42 is as defined in R 11 ,

iv) C(═Q 3 )NR 43 R 44 , wherein Q 3 is as defined in Q 1 , and R 43 and R 44 are the same or different and are as defined in R 13 and R 14 , respectively,

v) OR 45 , wherein R 45 is as defined in R 11 ,

vi) OCOR 46 , wherein R 46 is as defined in R 11 ,

vii) S(O)qR 47 , wherein q is an integer of 0 to 3, and R 47 is as defined in R 11 ,

viii) SO 2 NR 48 R 49 , wherein R 48 and R 49 are the same or different and are as defined in R 13 and R 14 , respectively,

ix) NR 50 R 51 , wherein R 50 and R 51 are the same or different and are as defined in R 21 and R 22 , respectively,

x) N(R 52 )C(═Q 4 )NR 53 R 54 , wherein Q 4 is as defined in Q 2 R 52 is as defined in R 11 , and R 53 and R 54 are the same or different and are as defined in R 13 and R 14 , respectively,

xi) N(R 55 )SO 2 NR 56 R 57 , wherein R 55 is as defined in R 11 , and R 56 and R 57 are the same or different and are as defined in R 13 and R 14 , respectively,

xii) SiR 58 R 59 R 60 , wherein R 58 , R 59 , and R 60 are the same or different and are each as defined in R 11 ,

xiii) a nitro group,

xiv) a cyano group, and

xv) a halogen atom.

2. The compound or salt of claim 1 , wherein, in formula (Ia), Z 3 is —CH═, and having a formula (Iaa):

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

wherein

each R 3 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) COR 11 , wherein R 11 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) COOR 12 , wherein R 12 is as defined in R 11 ,

v) C(═Q 1 )NR 13 R 14 , wherein Q 1 is an oxygen atom, a sulfur atom, or NR 15 (wherein R 15 is as defined in R 11 ); and R 13 and R 14 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 R 13 and R 14 together, which is a nitrogen-comprising heterocyclic group,

vi) OR 16 , wherein R 16 is as defined in R 11 ,

vii) OCOR 17 , wherein R 17 is as defined in R 11 ,

viii) S(O)pR 18 , wherein p is an integer of 0 to 3, and R 18 is as defined in R 11 ,

ix) SO 2 NR 19 R 20 , wherein R 19 and R 20 are the same or different and are as defined in R 13 and R 14 , respectively,

x) NR 21 R 22 ,wherein R 21 and R 22 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, COR 23 (wherein R 23 is as defined in R 11 ), COOR 24 (wherein R 24 is as defined in R 11 ), or SO 2 R 25 (wherein R 25 is as defined in R 11 ); or a group formed by linking R 21 and R 22 together, which is a nitrogen-comprising heterocyclic group,

xi) N(R 26 )C(═Q 2 )NR 27 R 28 , wherein, Q 2 represents an oxygen atom, a sulfur atom, or NR 29 (wherein R 29 is as defined in R 11 ), NCN, CHNO 2 or C(CN) 2 ; R 26 is as defined in R 11 ; and R 27 and R 28 are the same or different and are as in R 13 and R 14 , respectively,

xii) N(R 30 )SO 2 NR 31 R 32 , wherein R 30 is as defined in R 11 ; and R 31 and R 32 are the same or different and are as defined in R 13 and R 14 , respectively,

xiii) SiR 33 R 34 R 35 , wherein R 33 , R 34 , and R 35 are the same or different and are each as defined in R 11 ,

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;

Z 3 and Z 5 are the same or different and are —CH═ or —N═;

one of Z 4 and Z 6 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) COR 41 , wherein R 41 is as defined in R 11 ,

iii) COOR 42 , wherein R 42 is as defined in R 11 ,

iv) C(═Q 3 )NR 43 R 44 wherein Q 3 is as defined in Q 1 , and R 43 and R 44 are the same or different and are as defined in R 13 and R 14 , respectively,

v) OR 45 , wherein R 45 is as defined in R 11 ,

vi) OCOR 46 , wherein R 46 is as defined in R 11 ,

vii) S(O)qR 47 , wherein q is an integer of 0 to 3, and R 47 is as defined in R 11 ,

viii) SO 2 NR 48 R 49 , wherein R 48 and R 49 are the same or different and are as defined in R 13 and R 14 , respectively,

ix) NR 50 R 51 , wherein R 50 and R 51 are the same or different and are as defined in R 21 and R 22 , respectively,

x) N(R 52 )C(═Q 4 )NR 53 R 54 , wherein Q 4 is as defined in Q 2 R 52 is as defined in R 11 , and R 53 and R 54 are the same or different and are as defined in R 13 and R 14 , respectively,

xi) N(R 55 )SO 2 NR 56 R 57 , wherein R 55 is as defined in R 11 , and R 56 and R 57 are the same or different and are as defined in R 13 and R 14 , respectively,

xii) SiR 58 R 59 R 60 , wherein R 58 , R 59 , and R 60 are the same or different and are each as defined in R 11 ,

xiii) a nitro group,

xiv) a cyano group, and

xv) a halogen atom.

4. The compound or salt of claim 3 , wherein, in formula (Ib):

Z 3 and Z 6 are —N═;

Z 5 is —CH═ and

Z 4 is —S—, and

having a formula (Iba):

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

wherein

each R 3 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) COR 11 , wherein R 11 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) COOR 12 , wherein R 12 is as defined in R 11 ,

v) C(═Q 1 )NR 13 R 14 , wherein Q 1 is an oxygen atom, a sulfur atom, or NR 15 (wherein R 15 is as defined in R 11 ); and R 13 and R 14 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 R 13 and R 14 together, which is a nitrogen-comprising heterocyclic group,

vi) OR 16 , wherein R 16 is as defined in R 11 ,

vii) OCOR 17 , wherein R 17 is as defined in R 11 ,

viii) S(O)pR 18 , wherein p is an integer of 0 to 3, and R 11 is as defined in R 11 ,

ix) SO 2 NR 19 R 20 , wherein R 19 and R 20 are the same or different and are as defined in R 13 and R 14 , respectively,

x) NR 21 R 22 , wherein R 21 and R 22 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, COR 23 (wherein R 23 is as defined in R 11 , COOR 24 (wherein R 24 is as defined in R 11 ), or SO 2 R 25 (wherein R 25 is as defined in R 11 ); or a group formed by linking R 21 and R 22 together, which is a nitrogen-comprising heterocyclic group,

xi) N(R 26 )C(═Q 2 )NR 27 R 28 , wherein, Q 2 represents an oxygen atom, a sulfur atom, or NR 29 (wherein R 29 is as defined in R 11 ), NCN, CHNO 2 or C(CN) 2 ; R 26 is as defined in R 11 ; and R 27 and R 28 are the same or different and are as in R 13 and R 14 , respectively,

xii) N(R 30 )SO 2 NR 31 R 32 ,wherein R 30 is as defined in R 11 ; and R 31 and R 32 are the same or different and are as defined in R 13 and R 14 , respectively,

SiR 33 R 34 R 35 , wherein R 33 , R 34 , and R 35 are the same or different and are each as defined in R 11 ,

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;

Z 7 and Z 8 are the same or different and are —CH═ or —N═;

Z 9 is —O—, —S—, or —N(R 4 )—, wherein R 4 is a hydrogen atom, a substituted or unsubstituted alkyl group, or may form a ring together with an adjacent carbon atom through —(CH 2 ) 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) COR 41 , wherein R 41 is as defined in R 11 ,

iii) COOR 42 , wherein R 42 is as defined in R 11 ,

iv) C(═Q 3 )NR 43 R 44 , wherein Q 3 is as defined in Q 1 , and R 43 and R 44 are the same or different and are as defined in R 13 and R 14 , respectively,

v) OR 45 , wherein R 45 is as defined in R 11 ,

vi) OCOR 46 , wherein R 46 is as defined in R 11 ,

vii) S(O)qR 47 , wherein q is an integer of 0 to 3, and R 47 is as defined in R 11 ,

viii) SO 2 NR 48 R 49 , wherein R 48 and R 49 are the same or different and are as defined in R 13 and R 14 , respectively,

ix) NR 50 R 51 , wherein R 50 and R 51 are the same or different and are as defined in R 21 and R 22 , respectively,

x) N(R 52 )C(═Q 4 )NR 53 R 54 , wherein Q 4 is as defined in Q 2 R 52 is as defined in R 11 , R 53 and R 54 are the same or different and are as defined in R 13 and R 14 , respectively,

xi) N(R 55 )SO 2 NR 56 R 57 , wherein R 55 is as defined in R 11 , and R 56 and R 57 are the same or different and are as defined in R 13 and R 14 , respectively,

xii) SiR 58 R 59 R 60 , wherein R 58 , R 59 , and R 60 are the same or different and are each as defined in R 11 ,

xiii) a nitro group,

xiv) a cyano group, and

xv) a halogen atom.

6. The compound or salt of claim 5 , wherein, in formula (Ic):

Z 7 and Z 8 are —CH═; and

Z 9 is —O—, and

having a formula (Ica):

7. The compound or salt of claim 5 , wherein, in formula (Ic):

Z 7 and Z 8 are —CH═; and

Z 9 is —S—, and

having a formula (Icb):

8. 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]-2 40 -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]-3 1 -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.

9. A medicine, comprising a pharmaceutically acceptable carrier and the compound or salt of claim 1 .

10. An anticancer agent, comprising a pharmaceutically acceptable carrier and an active ingredient comprising the compound or salt of claim 1 .

11. A STAT3 inhibitor, comprising a pharmaceutically acceptable carrier and an active ingredient comprising the compound or salt of claim 1 .

12. A method of treating cancer in which STAT3 is activated, the method comprising:

administering an effective amount of the anticancer agent of claim 10 to a patient in need thereof.

13. A method for manufacturing an anticancer agent, the method comprising:

mixing the compound or salt of claim 1 with a pharmaceutically acceptable carrier.

14. A method of treating cancer in which STAT3 is activated, the method comprising:

administering an effective amount of the compound or salt of claim 1 to a patient in need thereof.

15. A medicine, comprising a pharmaceutically acceptable carrier and the compound or salt of claim 8 .

16. An anticancer agent, comprising a pharmaceutically acceptable carrier and an active ingredient comprising the compound or salt of claim 8 .

17. A STAT3 inhibitor, comprising a pharmaceutically acceptable carrier and an active ingredient comprising the compound or salt of claim 8 .

18. A method of treating cancer in which STAT3 is activated, the method comprising:

administering an effective amount of the anticancer agent of claim 16 to a patient in need thereof.

19. A method for manufacturing an anticancer agent, the method comprising:

mixing the compound or salt of claim 8 with a pharmaceutically acceptable carrier.

20. A method of treating cancer in which STAT3 is activated, the method comprising:

administering an effective amount of the compound or salt of claim 8 to a patient in need thereof.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 28, 2015
From: PHARMA DESIGN, INC.
To: KABUSHIKI KAISHA YAKULT HONSHA
Reel/Frame 036898/0400 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 3, 2012
From: ASAI, AKIRA; MATSUNO, KENJI; OGO, NAOHISA; TAKAHASHI, OSAMU; MASUDA, YOSHIAKI; MUROYA, AYUMU; AKIYAMA, YASUTO; ASHIZAWA, TADASHI; OKAWARA, TADASHI
To: GENERAL INCORPORATED ASSOCIATION PHARMA VALLEY PROJECT SUPPORTING ORGANIZATION; PHARMA DESIGN, INC.; SHIZUOKA PREFECTURE; KUMAMOTO HEALTH SCIENCE UNIVERSITY; KABUSHIKI KAISHA YAKULT HONSHA
Reel/Frame 028484/0441 →
Priority Claims (1)
JP 2009-297960 · Dec 28, 2009 · national
Continuity (1)
Related Publication 20120302524A1 · Nov 29, 2012