TH85267A

TH85267A - Substitutated carboxylic acid

Info

Publication number: TH85267A
Application number: TH501005085A
Authority: TH
Inventors: คอมบ์ส์ นายเคอร์รี่; ฮู นายเชาจิง; ไวท์เฮ้าส์ นายดาร์เรน; ซี แวน แซนด์ท์ นายไมเคิล
Original assignee: ดิ อินสติติวต์ส ฟอร์ ฟาร์มาซูติคอล ดิสคัฟเวอรี่; นางสาวปรับโยชน์ ศรีกิจจาภรณ์; นายจักรพรรดิ์ มงคลสิทธิ์; นายต่อพงศ์ โทณะวณิก; นายบุญมา เตชะวณิช
Filing date: 2005-10-28
Publication date: 2007-06-28

Abstract

DC60 (13/02/50) การประดิษฐ์นี้เกี่ยวกับสารประกอบ และเกลือที่เป็นที่ยอมรับทางเภสัชกรรมของสูตร I: (สูตรเคมี) I ซึ่งมีประโยชน์ในการบำบัดความผิดปกติเมแทบอลิคที่เกี่ยวกับความต้านทานอินซูลิน หรือ ภาวะเลือดมีน้ำตาลมาก สารประกอบเหล่านี้รวมถึง ตัวยับยั้งโปรตีนไทรอซีนฟอสฟาเทส (PTP-1B) ที่มีประโยชน์ในการบำบัดโรคเบาหวาน และโรคอื่นๆ ที่เป็นสื่อโดย PTP-1B, อย่างเช่น มะเร็ง, โรคเส้นประสาทเสื่อมและที่คล้ายกัน สารประกอบของการประดิษฐ์นี้มีประโยชน์ในสารผสมเชิง เภสัชกรรมและวิธีการบำบัดสภาวะที่กล่าวไว้ก่อนหน้านี้ด้วยเช่นกัน การประดิษฐ์นี้เกี่ยวกับสารประกอบ และเกลือที่เป็นที่ยอมรับทางเภสัชกรรมของสูตร I: (สูตรเคมี) I ซึ่งมีประโยชน์ในการบำบัดความปกติเมแทบอลิคที่เกี่ยวกับความต้านทานอินซูลิน หรือ ภาวะเลือดที่มีน้ำตาลมาก สารประกอบเหล่านี้รวมถึง ตัวยับยั้งโปรตีนไทรอซีนฟอสฟาเทส (PTP-1B) ที่มีประโยชน์ในการบำบัดโรคเบาหวาน และโรคอื่นๆ ที่เป็นสื่อโดย PTP-1B, อย่างเช่น มะเร็ง, โรคเส้นประสาทเสื่อมและที่คล้ายกัน สารประกอบของการประดิษฐ์นี้มีประโยชน์ในการผสมเชิง เภสัชกรรมและวิธีการบำบัดสภาวะที่กล่าวไว้ก่อนหน้านี้ด้วยเช่นกันDC60 (13/02/07) This invention relates to pharmaceutically acceptable compounds and salts of formula I: (chemical formula) I, which are useful in the treatment of metabolic disorders associated with insulin resistance or hyperglycemia. These compounds include protein tyrosine phosphatase (PTP-1B) inhibitors, which are useful in the treatment of diabetes mellitus and other PTP-1B-mediated diseases, such as cancer, neurodegenerative diseases, and the like. The compounds of the present invention are also useful in pharmaceutical formulations and methods for the treatment of the aforementioned conditions. This invention relates to pharmaceutically acceptable compounds and salts of formula I: (chemical formula) I, which are useful in the treatment of metabolic disorders associated with insulin resistance or hyperglycemia. These compounds include protein tyrosine phosphatase (PTP-1B) inhibitors, which are also useful in the treatment of diabetes mellitus and other PTP-1B-mediated diseases, such as cancer, neurodegenerative diseases, and the like. The compounds of the present invention are also useful in pharmaceutical formulations and methods for the treatment of the aforementioned conditions.

Claims

1. Compounds of the formula: (chemical formula) or their salts that are pharmaceutically acceptable, where k is 0 or 1; n is 0, 1, 2, 3, or 4; R1 is H, C1-C6 alkyl, phenyl(C1-C6)alkyl, or C3-C6 alkenyl; R2 is H, phenyl, phenyl(C1-C4)alkyl, C1-C6 alkyl, -(C1-C4)alkyl-C(O)NH2, -(C1-C4)alkyl-C(O)NH(C1-C4)alkyl, -(C1-C4)alkyl-C(O)N(C1-C4)alkyl. (C1-C4)alkyl, -(C1-C4)alkyl-S(O)b-(C1-C4)alkyl, (C1-C4)hydroxyalkyl, -(C1-C4)alkyl-heterocycloalkyl, which may selectively have the heterocycloalkyl group fused with the phenyl ring, and which may selectively have the heterocycloalkyl portion, the phenyl portion, or both replaced by a total of 1, 2, 3, or 4 independent groups: halogen, C1-C4alkyl, C1-C4alkoxy, -SO2-(C1-C4)alkyl, haloalkyl, or haloalkoxy; where b is 0, 1, or 2; the independent R20, R21, R22, and R23 are H, aryl alkoxy, aryl alkyl, halogen alkyl, haloalkyl, OH, alkoxy, NO2, NH2, NH(C1-C6)alkyl, N(C1-C6 alkyl) (C1-C6 alkyl), NH-aryl, NHC(O)-(C1-C4). Alkyl)-aryl, N(C1-C4 alkyl)C(O)- (C1-C4) alkyl-aryl, N(C1-C4) alkyl-aryl, -NHSO2-aryl, or -N(C1-C4 alkyl)SO2aryl, which may be chosen to have each of the above aryl groups replaced by 1, 2, 3, or 4 groups independently: C1-C6 alkyl, C1-C6 alkoxy, halogen, OH, NO2, haloalkyl, haloalkoxy; L represents C2-C6 alkynyls or C2-C6 alkynyls, which may be selectively replaced by phenyls, which may be selectively replaced by 1, 2, 3, or 4 independent groups: C1-C6 alkyls, C1-C6 alkoxys, halogens, OH, NO2, haloalkyls, or haloalkoxys; L3 represents a bond, absent, -(C1-C4)alkyl-O-, -O-(C1-C4)alkyl, -(C1-C4)alkyl-, -C(O)-, -C(O)NH-, or -NHC(O)-; Ring-A represents aryls selected from groups consisting of phenyl, naphthyl, and fluorenyl, or heteroaryls, which may be selected so that each group is independently replaced by 1, 2, or 3 groups: halogens, C1-C4 alkyls, C1-C4 alkoxy, C1-C4 haloalkyls, C1-C4 haloalkoxy, NO2, NH2, NH(C1-C6)alkyls, N(C1-C6)alkyls, (C1-C6)alkyls; Q is H, aryl, heteroaryl, -heteroaryl-alkyl, -aryl-heteroaryl, heterocycloalkyl, aryl-C(O)-aryl, aryl-(C1-C4 alkyl)-aryl, heteroaryl-(C1-C4 alkyl)-aryl, -heteroaryl-aryl, where the aryl group is phenyl, naphthyl, or fluorenyl, which may be independently substituted by 1, 2, 3, or 4 groups: C1-C6 alkyl, C1-C4 alkoxycarbonyl, C1-C6 alkoxy, halogen, haloalkyl, haloalkoxy, NR6R7, or phenyl; The independent R6 and R7 groups are H, C1-C6 alkyl, aryl(C1-C6) alkyl, alkanoyl, aryl alkanoyl, alkoxycarbonyl, aryl alkoxycarbonyl, heteroaryl carbonyl, heteroaryl, heterocycloalkyl carbonyl, -C(O)NH2, -C(O)NH(C1-C6) alkyl, -C(O)N(C1-C6) alkyl(C1-C6) alkyl, or -SO2-aryl, which may be selectively replaced by 1, 2, 3, or 4 independent cyclic groups: halogen, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2, NH(C1-C6) alkyl, N. (C1-C6)alkyl, haloalkyl, or haloalcoxi

2. Compounds according to claim 1, where R2 is H, phenyl, phenyl(C1-C4)alkyl, C1-C6alkyl, -(C1-C4)alkyl-C(O)NH2, -(C1-C4)alkyl-C(O)NH(C1-C4)alkyl, -(C1-C4)alkyl-C(O)N(C1-C4)alkyl (C1-C4)alkyl, -(C1-C4)alkyl-S(O)b-(C1-C4)alkyl, (C1-C4)hydroxyalkyl, -(C1-C4)alkyl-phthalimidyl, -(C1-C4)alkyl-piperidinyl, -(C1-C4)alkyl-pyrrolidinyl, -(C1-C4)alkyl-morpholinyl, which may selectively fuse phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyl groups with the phenyl ring, and which phthalimidyl, piperidinyl, pyrrolidinyl Or the aforementioned morpholin group is a part of phenyl, or either both could be replaced by groups that together form 1, 2, 3, or 4 groups independently: halogen, C1-C4 alkyl, C1-C4 alkoxy, -SO2-(C1-C4) alkyl(C1-C4)haloalkyl, or (C1-C4)haloalkoxy; where b is 0, 1, or 2; and Q is H, pirido[1,2-a]indolyl, indolyl, isoindolyl, indolicinyl, imidazo[1,2-a]piridine, -phenyl-C(O)-phenyl, -phenyl-(C1-C4)alkyl-phenyl, -piridyl-phenyl, fluorenyl, -fluorenyl-piridyl, fluorenyl-phenyl,-benzofuranyl-(C1-C4)alkyl-phenyl, -benzimidazoyl-(C1-C4)alkyl-phenyl, benzosazoyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, -indolyl-(C1-C4)alkyl-phenyl, -phenyl-benzosazolyl, benzo[b]thienyl, dibenzo[b,d]furan, tetrahydroquinolinyl, dihydroquinolinyl, phenyl, or dibenzothienyl, which may be selectively replaced by 1, 2, 3, or 4 independently named C1-C6 alkyl, C1-C4 alkoxycarbonyl, C1-C6 alkoxy, halogen, haloalkyl, haloalkoxy, NR6R7, or phenyl; The independent R6 and R7 groups are H, C1-C6 alkyl, aryl(C1-C6) alkyl, alkanoyl, phenyl(C1-C4) alkanoyl, alkoxycarbonyl, phenyl(C1-C4) alkoxycarbonyl, pyridylcarbonyl, pyridyl, piperidinyl, pyrrolidinylcarbonyl, -C(O)NH2, -C(O)NH(C1-C6) alkyl, -C(O)N(C1-C6) alkyl(C1-C6) alkyl, or -SO2-phenyl, which may have 1, 2, 3, or 4 cyclic groups replaced independently, namely halogens, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2. NH(C1-C6) alkyl, N(C1-C6) alkyl(C1-C6) alkyl, CF3 or OCF3

3. Compounds according to claim 2, in which ring-A is chosen from phenyl, naphthyl pyridyl, thiazolyl, benzofuranyl, dibenzofuranyl, pyrrolyl, furanyl, isoindolyl, or indolyl, which may be chosen to be replaced by 1, 2, or 3 independently of halogens, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, NO2, NH2, NH(C1-C6)alkyl, or N(C1-C6)alkyl(C1-C6)alkyl; And the independent R20, R21, R22, and R23 are H, phenyl alkoxy, phenyl alkyl, halogen, alkyl, CF3, OH, alkoxy, NO2, NH2, NH(C1-C6) alkyl, N(C1-C6) alkyl(C1-C6) alkyl, NH-phenyl, NHC(O)-(C1-C4) alkyl-phenyl, N(C1-C4 alkyl)C(O)-(C1-C4) alkyl-phenyl, N(C1-C4) alkyl-phenyl, -NHSO2-phenyl, or N(C1-C4 alkyl)SO2 phenyl, which may be selectively replaced by 1, 2, 3, or 4 independent groups, i.e., C1-C6 alkyl. C1-C6 alkoxy, halogen, OH, NO2, C1-C2 haloalkyl, or C1-C2 haloalkoxy

4. Compounds according to claim 3, where L is C2-C6 alkynyl or C2-C6 alkynyl, which may be selectively substituted with phenyl, which may be selectively substituted with 1, 2, 3, or 4 groups independently of C1-C6 alkyl, C1-C6 alkoxy, halogen, OH, NO2, C1-C4 haloalkyl, or C1-C4 haloalkoxy.

5. Compounds according to claim 4, of the formula (chemical formula) in which G is a bond or CR2; R1 is H or C1-C6 alkyl; R2 is H, phenyl, phenyl(C1-C4)alkyl, C1-C6 alkyl, -(C1-C4)alkyl-C(O)NH2, -(C1-C4)alkyl-S(O)b-(C1-C4)alkyl, or (C1-C4)hydroxyalkyl, which may be selectively substituted by 1, 2, 3, or 4 groups to which the phenyl group is independent: halogen, C1-C4 alkyl, C1-C4 alkoxy, -SO2-(C1-C4)alkyl, (C1-C4) haloalkyl, or (C1-C4) haloalkoxy; v is 0, 1, 2, 3, or 4; R10 at each independent location is halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, NO2, NH2, NH(C1-C6)alkyl, or N(C1-C6)alkyl(C1-C6)alkyl; and L3 is bonded, absent, -O-(C1-C4)alkyl, -C(C1-C4)alkyl-, or C(O)-.

6. Compounds according to claim 5, where Q is H, pirido[1,2-a]indolyl, indolyl, imidazo[1,2-a]piridine, -phenyl-C(O)-phenyl, -phenyl-(C1-C4)alkyl-phenyl, fluorenyl, benzofuranyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, -indolyl-(C1-C4)alkyl-phenyl, -phenyl-benzosazoyl, benzo[b]thienyl, dibenzo[b,d]furan, phenyl, or dibenzothienyl, which may be selectively substituted by 1, 2, 3, or 4 independent C1-C6 alkyl groups, C1-C4 alkoxycarbonyl, C1-C6 alkoxy, halogen, haloalkyl, haloalkoxy, NR6R7, or phenyl; The independent R6 and R7 groups are H, C1-C6 alkyl, aryl(C1-C6) alkyl, alkanoyl, phenyl(C1-C4) alkanoyl, alkoxycarbonyl, phenyl(C1-C4) alkoxycarbonyl, pyridyl carbonyl, pyridyl, pyrrolidinyl carbonyl, or SO2-phenyl, which may have 1, 2, 3, or 4 cyclic groups replaced by the independent halogen, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2, NH(C1-C6) alkyl, N(C1-C6) alkyl(C1-C6) alkyl, CF3, or OCF3.

7. Compounds according to claim 6, where R2 is H, phenyl, phenyl(C1-C4)alkyl, or (C1-C6)alkyl, which may be independently selected with the phenyl group replaced by 1, 2, 3, or 4 groups: halogen, C1-C4 alkyl, C1-C4 alkoxy, or -SO2-(C1-C4)alkyl, CF3 or OCF3; and R20, R21, R22, and R23 are independently selectable from H, halogen, alkyl, OH, alkoxy, NO2, NH2, NH(C1-C6)alkyl, or N(C1-C6 alkyl)(C1-C6 alkyl).

8. Compounds according to claim 7, where L3 is a bond, -O-(C1-C4)alkyl, -(C1-C4)alkyl-, or -C(O)-; Q is indolyl, -phenyl-C(O)-phenyl, -benzofuranyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, -indolyl-(C1-C4)alkyl-phenyl, benzo[b]thienyl, diben[b,d]furan, phenyl, or dibenzothienyl, which may be chosen to be independently substituted by 1, 2, 3, or 4 groups: C1-C6 alkyl, C1-C4 alkoxycarbonyl, C1-C6 alkoxy, halogen, haloalkyl, Haloalkoxy, NR6R7, or phenyl; where the independent R6 and R7 are H, C1-C6 alkyl, phenyl(C1-C6) alkyl, alkanoyl, phenyl(C1-C4) alkanoyl, alkoxycarbonyl, pyridyl carbonyl, pyridyl, pyrrolidinyl carbonyl, or -SO2-phenyl, which may have 1, 2, 3, or 4 independent cyclic groups substituted: halogen, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2, NH(C1-C6) alkyl, N(C1-C6) alkyl(C1-C6) alkyl, CF3, or OCF3.

9. Compounds according to claim 8, where L is C2-C6 alkynyl or C2-C6 alkynyl, which may be selectively substituted with phenyl, which may be selectively substituted with 1, 2, 3, or 4 groups independently of C1-C6 alkyl, C1-C6 alkoxy, halogen, OH, NO2, C1-C4 haloalkyl, or C1-C4 haloalkoxy.

10. Compounds according to claim 9, where R1 is H, R21 is H, NO2, C1-C6 alkyl, or halogen; and R2 is phenyl, benzyl, or (C1-C6)alkyl, where each phenyl group may be independently substituted by 1, 2, 3, or 4 groups: halogen, C1-C4 alkyl, C1-C4 alkoxy, or -SO2-(C1-C4)alkyl, CF3, or OCF3.

11. Compounds according to claim 10, where L3 is a bond, -O-(C1-C4)alkyl, or -(C1-C4)alkyl-; Q is -benzofuranyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, dibenzo[b,d]furan, or dibenzothienyl, which may be chosen to be independently substituted by 1, 2, 3, or 4 groups: C1-C6alkyl, C1-C4alkoxycarbonyl, C1-C6alkoxy, halogen, haloalkyl, haloalkoxy, NR6R7, or phenyl; The independent R6 and R7 groups are H, C1-C6 alkyl, phenyl(C1-C6) alkyl, alkanoyl, phenyl(C1-C4) alkanoyl, alkoxycarbonyl, pyridyl carbonyl, pyridyl, pyrrolidinyl carbonyl, or -SO2-phenyl, which may have 1, 2, 3, or 4 cyclic groups replaced independently: halogen, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2, NH (C1-C6) alkyl, N(C1-C6) alkyl(C1-C6) alkyl, CF3, or OCF3.

12. Compounds according to claim 8, where L is a C2-C6 alkynyl or C2-C6 alkynyl,

13. Compounds according to claim 12, where R1 is H; R21 is H, NO2, C1-C6 alkyl, or halogen; and R2 is H, phenyl, phenyl(C1-C4)alkyl, or (C1-C6)alkyl, which may be chosen so that each phenyl group is independently replaced by 1, 2, 3, or 4 groups: halogen, C1-C4 alkyl, C1-C4 alkoxy, or -SO2-(C1-C4)alkyl, CF3, or OCF3.

14. Compounds according to claim 13, where L3 is a bond, -O-(C1-C4)alkyl, or -(C1-C4)alkyl-; Q is indolyl, -phenyl-C(O)-phenyl,-benzofuranyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, or -indolyl-(C1-C4)alkyl-phenyl, which may be selectively substituted by 1, 2, 3, or 4 independent groups: C1-C6alkyl, C1-C4alkoxycarbonyl, C1-C6alkoxy, halogen, haloalkyl, haloalkoxy, NR6R7, or phenyl; The independent R6 and R7 groups are H, C1-C6 alkyl, phenyl (C1-C6) alkyl, alkanoyl, phenyl (C1-C4) alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyrrolidinyl, carbonyl, or -SO2-phenyl, which may have 1, 2, 3, or 4 cyclic groups replaced independently: halogen, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2, NH (C1-C6) alkyl, N (C1-C6) alkyl (C1-C6) alkyl, CF3, or OCF3.

15. Compounds according to claim 8, where L is C2-C6 alkynyl or C2-C6 alkynyl, which may be selectively substituted with phenyl, which may be selectively substituted with 1, 2, 3, or 4 groups independently of C1-C6 alkyl, C1-C6 alkoxy, halogen, OH, NO2, C1-C2 haloalkyl, or C1-C2 haloalkoxy.

16. Compounds according to claim 13, where L is C2-C6 alkynyl or C2-C6 alkynyl; R1 is H; R21 is H, NO2, C1-C6 alkyl, or halogen.

17. The compounds under claim 16 R2 are phenyl, phenyl(C1-C4)alkyl, or (C1-C6)alkyl, which may be selectively substituted by 1, 2, 3, or 4 independent groups of phenyl, halogen, C1-C4 alkyl, C1-C4 alkoxy, or -SO2-(C1-C4)alkyl, CF3, or OCF3.

18. Compounds according to claim 17, where L3 is a bond, -O-(C1-C4)alkyl, or -(C1-C4)alkyl-; Q is indolyl, -phenyl-C(O)-phenyl,-benzofuranyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, or -indolyl-(C1-C4)alkyl-phenyl, which may be selectively substituted by 1, 2, 3, or 4 independent groups: C1-C6alkyl, C1-C4alkoxycarbonyl, C1-C6alkoxy, halogen, haloalkyl, haloalkoxy, NR6R7, or phenyl; The independent R6 and R7 groups are H, C1-C6 alkyl, phenyl(C1-C6) alkyl, alkanoyl, phenyl(C1-C4) alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyrrolidinyl-carbonyl, or -SO2-phenyl, which may have 1, 2, 3, or 4 cyclic groups replaced independently: halogen, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2, NH(C1-C6) alkyl, N(C1-C6) alkyl(C1-C6) alkyl, CF3, or OCF3.

19. Compounds according to claim 5, where L is a C2-C6 alkenyl or C2-C6 alkinyl.

20. Compounds according to claim 19, where R1 is H; R21 is H, NO2, C1-C6 alkyl, or halogen; and R2 is H, phenyl, phenyl(C1-C4)alkyl, (C1-C6)alkyl, -(C1-C4)alkyl-C(O)NH2, -(C1-C4)alkyl-S(O)b-(C1-C4)alkyl, or (C1-C4)hydroxyalkyl, which may be selectively substituted by 1, 2, 3, or 4 groups to be halogens, C1-C4 alkyl, C1-C4 alkoxy, -SO2-(C1-C4)alkyl, CF3 or OCF3.

21. Compounds according to claim 20, where L3 is a bond, -O-(C1-C4)alkyl, or -(C1-C4)alkyl-; Q is indolyl, -phenyl-C(O)-phenyl,-benzofuranyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, or -indolyl-(C1-C4)alkyl-phenyl, which may be selectively substituted by 1, 2, 3, or 4 independent groups: C1-C6alkyl, C1-C4alkoxycarbonyl, C1-C6alkoxy, halogen, haloalkyl, haloalkoxy, NR6R7, or phenyl; The independent R6 and R7 groups are H, C1-C6 alkyl, phenyl(C1-C6) alkyl, alkanoyl, phenyl(C1-C4) alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyrrolidinyl, carbonyl, or -SO2-phenyl, which may have 1, 2, 3, or 4 cyclic groups replaced independently: halogen, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2, NH(C1-C6) alkyl, N(C1-C6) alkyl(C1-C6) alkyl, CF3, or OCF3.

21. Compounds according to claim 2, of the formula: (chemical formula) where G is a bond or CR2; v is 0,1,2,3, or 4; R10 at each independent location is a halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, NO2, NH2, NH(C1-C6)alkyl, or N(C1-C6)alkyl(C1-C6)alkyl; L represents C2-C6 alkynyls or C2-C6 alkynyls, each of which may be selectively replaced by phenyls, which may be independently replaced by 1, 2, 3, or 4 groups: C1-C6 alkyls, C1-C6 alkoxys, halogens, OH, NO2, C1-C4 haloalkyls, or C1-C4 haloalkoxys.

23. Compounds according to claim 22, where R1 is H; R20, R22, and R23 are independently selectable from H, halogens, alkyls, OH, alkoxy, NO2, NH2, NH(C1-C6)alkyl, or N(C1-C6alkyl)(C1-C6alkyl); R21 is H, NO2, C1-C6alkyl, or halogens; And R2 is H, phenyl, phenyl(C1-C4)alkyl, C1-C6alkyl, -(C1-C4)alkyl-phthalimidyl, -(C1-C4)alkyl-piperidinyl, -(C1-C4)alkyl-pyrrolidinyl, -(C1-C4)alkyl-morpholinyl, which may be chosen to have the phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyl groups fused with the phenyl ring and in which the phthalimidyl, piperidinyl, pyrrolidinyl, or the aforementioned morpholinyl groups are parts of phenyl, or it may be chosen to Both are replaced by groups that are collectively 1, 2, 3, or 4, independently of which b is halogen, C1-C4 alkyl, C1-C4 alkoxy, -SO2-(C1-C4)alkyl, (C1-C4)halo alkyl, or (C1-C4)halo alkoxy; where b is 0, 1, or 2.

24. Compounds according to claim 20, where L3 is a bond, -O-(C1-C4)alkyl, or -(C1-C4)alkyl-; Q is indolyl, -phenyl-C(O)-phenyl, -benzofuranyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, -indolyl-(C1-C4)alkyl-phenyl, dibenzo[b,d]furan, or dibenzothienyl, which may be selectively substituted by 1, 2, 3, or 4 independent groups: C1-C6alkyl, C1-C4alkoxycarbonyl, C1-C6alkoxy, halogen, haloalkyl, haloalkoxy, NR6R7, or phenyl; The independent R6 and R7 groups are H, C1-C6 alkyl, phenyl(C1-C6) alkyl, alkanoyl, phenyl(C1-C4) alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyrrolidinyl, carbonyl, or -SO2-phenyl, which may have 1, 2, 3, or 4 cyclic groups replaced independently: halogen, C1-C4 alkyl, C1-C4 alkoxy, NO2, OH, NH2, NH(C1-C6) alkyl, N(C1-C6) alkyl(C1-C6) alkyl, CF3, or OCF3.

25. Compounds according to claim 24, where R2 is H, -(C1-C4)alkyl-phthalimidyl, -(C1-C4)alkyl-piperidinyl, -(C1-C4)alkyl-pyrrolidinyl, -(C1-C4)alkyl-morpholinyyl, which may be selectively fused with phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyyl groups to a phenyl ring, and where phthalimidyl, piperidinyl, pyrrolidinyl, Or the aforementioned morpholin group is a part of phenyl, or either both could be replaced by groups that together form 1, 2, 3, or 4 groups independently: halogen, C1-C4 alkyl, C1-C4 alkoxy, -SO2-(C1-C4) alkyl(C1-C4)haloalkyl, or (C1-C4)haloalkoxy.

26. Compounds according to claim 25, where L3 is a bond, -O-(C1-C4)alkyl, or -(C1-C4)alkyl-; Q is indolyl, -benzofuranyl-(C1-C4)alkyl-phenyl, indolicinyl, benzofuranyl, -indolyl-(C1-C4)alkyl-phenyl, or dibenzofuran, which may be chosen to be independently replaced by 1, 2, 3, or 4 groups: C1-C6 alkyl, C1-C4 alkoxycarbonyl, C1-C6 alkoxy, halogen, CF3 or OCF3.

27. A pharmaceutical mixture containing the compounds specified in claim 1 and at least one pharmaceutically acceptable solvent, carrier, filler, or excipient.

28. The use of the compounds of claim 1 or the pharmaceutical mixtures of claim 27 in the manufacture of drugs for the treatment of diabetes in patients requiring the aforementioned treatment.

29. Selected compounds under Recourse I consisting of the following groups: methyl (3E)-4-[4'-(1-benzofuran-2-yl)biphenyl-4-yl]-2-phenylbut-3-enoate, methyl (3E)-4-(4'-{[3-(cyclohexa-2,4-diene-1-ylcarbonyl)phenoxy]methyl}biphenyl-4-yl)-2-phenylbut-3-enoate, (3E)-2-benzyl-4-[4'-(2-benzyl-4-fluoro-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]but-3-enoic acid. (3E)-4-[4'-(2-benzyl-1-benzofuran-3-il) biphenyl-4-il]-2-ethylbut-3-enoic acid (3E)-4-(4'-dibenzofuran-4-il biphenyl-4-il)-2-[3-(trifluoromethyl)benzyl]but-3-enoic acid; 2-benzyl-4-[4'-(2-benzyl-1-benzofuran-3-il)-biphenyl-4-il]-but-3-enoic acid 3-(4'-dibenzofuran-4-il-biphenyl-4-il)-acrylic acid; 3-(4'-dibenzofuran-4-il-bifen-4-il)-acrylic acid; or its pharmaceutically acceptable salts.