Insulin derivatives

1. The insulin derivative having the formula

wherein Ins is the parent insulin moiety which via the α-amino group of the N-terminal amino acid residue of the B chain or an ε-amino group of a Lys residue present in the B chain of the insulin moiety is bound to the CO— group in the side chain via an amide bond;

X 1 is a bond,

W is a bond;

m is 0;

X is a bond;

Y is —(CR 1 R 2 ) q —NR—CO—, where R 1 and R 2 independently of each other and independently for each value of q can be H, —COOH, a bond or OH provided R 1 on the carbon alpha to the amide group is COOH, q is 3; and R is hydrogen or —(CH 2 ) p —COOH; —(CH 2 ) p —SO 3 H; —H (CH 2 ) p —PO 3 H 2 ; —(CH 2 ) p —O—PO 3 H 2 ; arylene substituted with 1 or 2 —(CH 2 ) p —O—COOH groups; —(CH 2 ) p -tetrazolyl, where p is an integer in the range of 1 to 6;

Q is a divalent hydrocarbon chain of the formula

—(CH 2 ) s -Q 1 -(C 6 H 4 ) v1 -Q 2 -(CH 2 ) W -Q 3 -(C 6 H 4 ) v2 -Q 4 -(CH 2 ) t -Q 5 -(C 6 H 4 ) v3 -Q 6 -(CH 2 ) z —

wherein Q 1 and Q 2 -Q 6 independently of each other can be O; S or a bond; where s is 2 and w, t and z independently of each other are zero or an integer from 1 to 10 so that the sum of s, w, t and z is in the range from 4 to 22, and v 1 is 1 v 2 , and v 3 independently of each other can be zero or 1,

provided that when W is a bond then Q is not a divalent hydrocarbon chain of the formula—(CH 2 ) v4 C 6 H 4 (CH 2 ) W1 — wherein v 4 and w 1 are integers or one of them is zero so that the sum of v 4 and w 1 is in the range of 6 to 22; and

Z is selected from the group consisting of: —COOH; —CO-Asp; —CO-Glu; —CO-Gly; —CO-Sar; —CH(COOH) 2 ; —N(CH 2 COOH) 2 ; —SO 3 H; —PO 3 H 2 ; O—SO 3 H; O—PO 3 H 2 ; -tetrazolyl and —O—W 1 , where W 1 is arylene or heteroarylene substituted with one or two groups selected from —COOH, —SO 3 H, and —PO 3 H 2 and tetrazolyl;

provided that if W is a bond and v 1 , v 2 and v 3 are all zero and Q 1-6 are all a bond, then Z is O—W 1 and any Zn 2+ complex thereof.

2. The insulin derivative according to claim 1 , wherein Z is —COOH.

3. The insulin derivative according to claim 1 , wherein the parent insulin moiety is a des(B30) human insulin or an analogue thereof.

4. The insulin derivative according to claim 1 , wherein the parent insulin moiety is selected from the group consisting of human insulin; des(B1) human insulin;

desB30 human insulin; GlyA21 human insulin; GlyA21des(B30)human insulin; AspB28 human insulin; porcine insulin; LysB28ProB29 human insulin; GlyA21ArgB31ArgB32 human insulin; and

LysB3GluB29 human insulin.

5. The insulin derivative according to claim 1 selected from the group consisting of:

N εB29 -{4-Carboxy-4-[10-(4-carboxy-phenoxy)-decanoylamino]-butyryl}desB30 human insulin,

N εB29 -3-[4′-(2-Carboxyethyl)biphenyl-4-yl]propionyl-γ-L-glutamyl desB30 human insulin,

N εB29 —{4-[2-(4-carboxymethylphenyl)ethyl]phenyl}acetyl-γ-L-glutamyl desB30 human insulin,

N εB29 -10-(4-carboxyphenylsulfanyl)decanoyl-γ-L-glutamyl desB30 human insulin, N εB29 -11-(4-carboxylphenylsulfanyl)undecanoyl-γ-L-glutamyl desB30 human insulin, N εB29 -10-(4-carboxyphenoxy)decanoyl beta-Asp desB30 human insulin, N εB29 -11-(4-carboxy-phenoxy)undecanoyl-γ-L-glutamyl desB30 human insulin.

6. A pharmaceutical composition for the treatment of diabetes in a patient in need of such treatment, said composition comprising a therapeutically effective amount of an insulin derivative according to claim 1 .