Patent ID: 7268213
Filing Date: 2007-09-11
Classification: A61K,A61P,C07K

Abstract:
1. A compound of formula (I), wherein A 7 is L-His, Ura, Paa, Pta, Amp, Tma-His, des-amino-His, or deleted; A 8 is D-Ala, Aib, Acc, N-Me-Ala, N-Me-D-Ala or N-Me-Gly; A 9 is Glu, N-Me-Glu, N-Me-Asp or Asp; A 10 is Gly, Acc, β-Ala or Aib; A 11 is Thr or Ser; A 12 is Phe, Acc, Aic, Aib, 3-Pal, 4-Pal, β-Nal, Cha, Trp or X 1 -Phe; A 13 is Thr or Ser; A 14 is Ser or Aib; A 15 is Asp or Glu; A 16 is Val, Acc, Aib, Leu, Ile, Tle, Nle, Abu, Ala or Cha; A 17 is Ser or Thr; A 18 is Ser or Thr; A 19 is Tyr, Cha, Phe, 3-Pal, 4-Pal, Acc, β-Nal or X 1 -Phe; A 20 is Leu, Acc, Aib, Nie, Ile, Cha, Tle, Val, Phe or X 1 -Phe; A 21 is Glu or Asp; A 22 is Gly, Acc, β-Ala, Glu or Aib; A 23 is Gln, Asp, Asn or Glu; A 24 is Ala, Aib, Val, Abu, Tle or Acc; A 25 is Ala, Aib, Val, Abu, Tle, Acc, Lys, Arg, hArg, Orn, HN—CH((CH2) n —N(R 10 -R 11 ))—C(O) or NH—CH((CH 2 ) e —X 3 )—C(O); A 26 is Lys, Arg, hArg, Orn, HN—CH((CH 2 ) n —N(R 10 -R 11 ))—C(O) or NH—CH((CH 2 ) e —X 3 )—C(O); A 27 is Glu Asp, Leu, Aib or Lys; A 28 is Phe, Pal, β-Nal, X 1 -Phe, Aic, Acc, Aib, Cha or Trp; A 29 is Ile, Ace, Aib, Leu, Nie, Cha, Tle, Val, Abu, Ala or Phe; A 30 is Ala, Aib or Acc; A 31 is Trp, β-Nal, 3-Pal, 4-Pal, Phe, Acc, Aib or Cha; A 32 is Leu, Acc, Aib, Nle, Ile, Cha, Tle, Phe, X 1 -Phe or Ala; A 33 is Val, Acc, Aib, Leu, Ile, Tle, Nie, Cha, Ala, Phe, Abu, Lys or X 1 -Phe; A 34 is Lys, Arg, hArg, Orn, HN—CH((CH 2 ) n -N(R 10 -R 11 ))—C(O) or NH—CH((CH 2 ) e —X 3 )—C(O); A 35 is β-Ala, D-Ala, Gaba, Ava, NH—(CH 2 ) m —C(O), Aib, Acc or a D-amino acid; A 36 is L-or D-Arg, D-or L-Lys, D-or L-hArg, D-or L-Orn, HN—CH((CH 2 ) n —N(R 10 -R 11 ))—C(O), NH—CH((CH 2 ) e —X 3 )—C(O) or deleted; A 37 is Gly, β-Ala, Gaba, Ava, Aib, Acc, Ado, Arg, Asp, Aun, Aec, NH—(CH 2 ) m —C(O), HN—CH ((CH 2 ) n —N(R 10 -R 11 ))—C(O), a D-amino acid, or deleted; A 38 is D-or L-Lys, D-or L-Arg, D-or L-hArg, D-or L-Orn, HN—CH((CH 2 ) n —N(R 10 -R 11 ))—C(O), NH—((CH 2 ) e -X 3 )—C(O), Ava, Ado, Aec or deleted; A 39 is D-or L-Lys, D-or L-Arg, HN—CH((CH 2 ) n —N(R 10 -R 11 ))—C(O), Ava, Ado, or Aec; X 1 for each occurrence is independently selected from the group consisting of (C 1 -C 6 )alkyl, OH and halo; R 1 is OH, NH 2 , (C 1 -C 30 ) alkoxy, or NH—X 2 —CH 2 -Z 0 , wherein X 2 is a (C 1 -C 12 ) hydrocarbon moiety, and Z 0 is H, OH, CO 2 H or CONH 2 ; or —C(O)—NHR 2 , wherein X 4 is, independently for each occurrence, —C(O)—, —NH—C(O)— or —CH 2 —, and wherein f is , independently for each occurrence, an integer from 1 to 29 inclusive; each of R 2 and R 3 is, independently for each occurrence, H; e is, independently for each occurrence, an integer from 1 to 4 inclusive; m is, independently for each occurrence, an integer from 5 to 24 inclusive; n is, independently for each occurrence, an integer from 1 to 5, inclusive; each of R 10 and R 11 is, independently for each occurrence, H, (C 1 -C 30 )alkyl, (C 1 -C 30 )acyl, (C 1 -C 30 )alkylsulfonyl, —C((NH)(NH 2 )) or and R 12 and R 13 each is, independently for each occurrence, (C 1 -C 30 )alkyl; provided that: (i) when A (ii) when R then R 11 is H or (C 1 -C 30 )alkyl; (iii) at least one amino acid of a compound of formula (I) is not the same as the native sequence of hGLP-1(7-36, -34, -35, -37 or -38)NH (iv) a compound of formula (I) is not an analogue of hGLP-1(7-36, -37 or -38)NH (v) a compound of formula (I) is not (Arg (vi) a compound of formula (I) is not (Z (vii) a compound of formula (I) is not a combination of any two of the substitutions listed in groups (vi)(a) to (vi)(d); and (viii) a compound of formula (I) is not (N-Me-Ala