METAP2 inhibitors and methods of treating obesity
AssigneeSynDevRx, Inc.
InventorsJohn S. Petersen, James Shanahan
Life of this patent
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Abstract
The present invention relates to modified or polymer conjugated MetAP2 inhibitors. The present invention also relates to methods of preventing, inducing, causing or increasing weight loss, treating obesity and/or treating metabolic syndrome utilizing the modified or polymer conjugated MetAP2 inhibitors. The present invention also relates to methods of improving insulin sensitivity and glycemic control, reducing insulin levels and/or improving leptin sensitivity utilizing the modified or polymer conjugated MetAP2 inhibitors.
Claims47
A method for lowering or decreasing blood glucose levels in a subject in need thereof, comprising administering at least one compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of
- in a therapeutically effective amount to the subject.
A method for lowering or decreasing blood glucose levels in a subject in need thereof comprising administering at least one compound, or a pharmaceutically acceptable salt thereof, of the Formula
- wherein, independently for each occurrence,
- R4 is H or C1-C6 alkyl;
- R5 is H or C1-C6 alkyl;
- R6 is C2-C6 hydroxyalkyl;
- Z is —NH-AA1-AA2-AA3-AA4-AA5-AA6-C(O)-Q-X-Y—C(O)—W;
- AA1 is glycine, alanine, or H2N(CH2)mCO2H, wherein m is 2, 3, 4 or 5;
- AA2 is a bond, or alanine, cysteine, aspartic acid, glutamic acid, phenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, valine, tryptophan, or tyrosine;
- AA3 is a bond, or alanine, cysteine, aspartic acid, glutamic acid, phenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, valine, tryptophan, or tyrosine;
- AA4 is a bond, or alanine, cysteine, aspartic acid, glutamic acid, phenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, valine, tryptophan, or tyrosine;
- AA5 is a bond, or glycine, valine, tyrosine, tryptophan, phenylalanine, methionine, leucine, isoleucine, or asparagine;
- AA6 is a bond, or alanine, asparagine, citrulline, glutamine, glycine, leucine, methionine, phenylalanine, serine, threonine, tryptophan, tyrosine, valine, or H2N(CH2)mCO2H, wherein m is 2, 3, 4 or 5;
- Q is NR, O, or S;
- X is M-(C(R)2)p-M-J-M-(C(R)2)p-M-V;
- M is a bond, or C(O);
- J is a bond, or ((CH2)qQ)r, C5-C8 cycloalkyl, aryl, heteroaryl, NR, O, or S;
- Y is NR, O, or S;
- R is H or alkyl;
- V is a bond or
- R9 is alkyl, aryl, aralkyl, or a bond;
- or R9 taken together with Y forms a heterocyclic ring;
- R10 is amido or a bond;
- R11 is H or alkyl;
- W is a methionine aminopeptidase-2 inhibitor moiety according to the following structure:
- x is in the range of 1 to about 450;
- y is in the range of 1 to about 30;
- n is in the range of 1 to about 50;
- p is 0 to 20;
- q is 2 or 3;
- and
- r is 1, 2, 3, 4, 5, or 6;
- in a therapeutically effective amount to the subject.
Dependencies are inferred from the claim text.