Table 2 Percentage of blockade of TRPV1 and TRPM8 channels by peptide- and amide-derived β–lactams.

From: Synthesis, high-throughput screening and pharmacological characterization of β–lactam derivatives as TRPM8 antagonists

Compound

R 2

X-R 3

R 4

R 5

R 6

n

% Block TRPV1 50 µM

% Block TRPM8 50 µM

IC 50 TRPM8 (μM)

56a

L-Phe-OMe

L-Phe-OMe

H

Boc

H

1

16.8 ± 10.4

99.3 ± 3.4

9.30 ± 1.0

56b

L-Phe- OMe

L-Phe-OMe

H

Boc

H

1

12.4 ± 10.8

99.3 ± 7.7

8.41 ± 1.4

57a

L-Ala-OMe

L-Ala-OMe

H

Boc

H

1

10.3 ± 11.9

33.7 ± 11.7

75.2 ± 1.9

57b

L-Ala-OMe

L-Ala-OMe

H

Boc

H

1

—

44.0 ± 16.5

70.4 ± 1.6

58

L-Ala-OMe

OBn

H

Z

H

2

18.3 ± 16.2

50.7 ± 9.5

48.41 ± 18.6

59

D-Ala-OMe

OMe

H

Z

H

2

19.4 ± 5.1

36.2 ± 22.3

81.2 ± 4.8

60

L-Ala-OMe

OMe

Me

Z

H

2

—

71.3 ± 18.8

32.6 ± 1.8

61

L-Ala-OMe

OMe

Me

H

H

2

—

78.3 ± 25.0

27.0 ± 1.7

62a

Bn

NHBn

H

Boc

H

1

42.5 ± 16.2

70.0 ± 18.6

7.1 ± 0.3

63a

Bn

NHBn

H

Boc

Me (R)

1

15.2 ± 11.8

100

5.7 ± 1.2

63b

Bn

NHBn

H

Boc

Me (S)

1

13.0 ± −9.0

100

8.3 ± 1.1

64

Bn

NHBn

H

Boc

H

2

26.9 ± 9.2

70.4 ± 15.2

11.5 ± 2.7

65

CH2(4-Py)

NHCH2(4-Py)

H

Boc

H

1

7.4 ± 9.5

39.3 ± 14.7

55.5 ± 2.3

66

(3-Py)

NH(3-Py)

H

Boc

H

1

22.8 ± 3.7

64.6 ± 13.2

5.7 ± 3.4

67a

(4-Py)

NH(4-Py)

H

Boc

H

1

36.3 ± 10.8

43.5 ± 9.8

38.13 ± 6.3

67b

(4-Py)

NH(4-Py)

H

Boc

H

1

31.7 ± 4.5

52.3 ± 7.6

7.26 ± 1.9

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