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Mukesh Chandra Sharma et al /Int.J. PharmTech Res.2010,2(2)

1379

Model 4 Log10 (IC_50) = + 0.8838 H-Donor Count + 0.6714 T_2_Cl_6 + 0.6073 chi5chain+0.5364 +0.394 T_N_N_5 - 0.3801 T_2_O_4 + 3.6338 Optimum Components = 3, Degrees of Freedom = 13, n = 16, r2= 0.7481 q2= 0.5673, F test 59.01 r2 se = 0 . 6 2 5 1 , q 2 s e = 0 . 5 4 8 1 , p r e d _ r 2 = 0 . 7 0 3 6 , S E E = 0 . 2 9 1 , SECV= 0.167, SEP=0.193, best_ran_r2 = 0.136, = 0.201, b e s t _ r a n _ = 0.126, Zscore ra n r2 q 2 Zscore_ran_q2 _ran_q2 = <0.01 _ α_ran_r2 _ = = 0.048, <0.00001, α

Model – 3 shows good squared correlation coefficient (r2) of 0. 7036 explains 70.36% variance in biological activity. This model also indicates statistical significance >99.9% with F values F = 59.01. Cross validated squared correlation coefficient of this model was 0.5481, which shows the good internal prediction

power of this model. The graph of observed vs. predicted biological activities for the training and the test molecules is shown in Figure. In the above equations n is the number of compounds used to derive the model and values in parentheses are the 95% confidence limit of respective coefficient.

CONCLUSION Models have given significant information to build a strategy to improve the biological activity of the compounds. Substituted methyl and ethyl groups at R are essential for the biological activity. The CF3 group at R4 gives compounds with better biological activity than the ethyl substituents. The electrostatic contribution of 2-Pyridyl and 3-Pyridyl groups at R3 led to compounds with good selectivity over PPARα and potent PPAR γ/δ affinity and functional activity. 1

Table-1 Substituted 3-{4-[3-(2-aryl-phenoxy) butoxy]-phenyl} propionic acids With IC50

and PIC50 values

Comp.

Polarizability

Polarizability

chi1

1-path

chi3cluster

kappa3

Hydrogen

SaaCH

SdssC

AHC

AHP

count

count

count

count

O

O

  • O

    O

1mol2

51.841933

51.936

15.939892

35

2.044998

9.520661

34

11

1

8 mol2

45.062825

48.362

15.456729

34

1.976957

8.628099

31

6

2

9 mol2

45.062825

48.362

15.456729

34

1.976957

8.628099

31

6

2

10 mol2

46.838624

46.897

14.956729

33

1.976957

8.065844

30

9

1

11 mol2

49.105921

49.392

15.456729

34

1.976957

8.628099

31

10

1

12 mol2

49.105921

49.392

15.456729

34

1.976957

8.628099

31

10

1

13 mol2

49.105921

49.392

15.456729

34

1.976957

8.628099

31

10

1

14 mol2

47.684271

48.674

14.956729

33

1.976957

8.065844

29

8

1

15 mol2

47.684271

48.674

14.956729

33

1.976957

8.065844

29

8

1

17 mol2

45.885679

46.248

14.956729

33

1.976957

8.065844

29

8

1

18mol2

47.304559

47.65

14.918724

33

2.061508

8.373087

26

10

1

19 mol2

46.642874

47.284

16.130049

36

1.91717

9.119219

26

10

1

21 mol2

49.315506

49.828

16.668054

37

1.848135

9.356625

29

11

1

7mol2

50.00065

50.101

15.45673

34

1.976957

8.628099

32

11

1

20mol2

50.94605

51.227

15.99473

35

1.907921

8.864266

33

10

1

16mol2

45.88568

46.248

14.95673

33

1.976957

8.065844

29

8

1

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