249 results about "Peptidase P" patented technology

The invention discloses certain N-(substituted glycyl)-pyrrolidines, pharmaceutical compositions containing said compounds as an active ingredient thereof, and the use of said compounds in inhibiting dipeptidyl peptidase-IV.

The present invention relates to a series of prodrugs of inhibitors of DP-IV with improved properties. The compounds can be used for the treatment of a number of human diseases, including impaired glucose tolerance and type II diabetes. The compounds of the invention are described by general formula (1); wherein R1 is H or CN; R2 is selected from CH2R5, CH2CH2R5 and C(R3)(R4)—X2—(CH2)aR5; R3 and R4 are each independently selected from H and Me; R5 is selected from CON(R6)(R7), N(R8)C(=0)R9, N(R8)C(═S)R9, N(R8)SO2R10 and N(R8)R10; R6 and R7 are each independently R11(CH2)b or together they are —(CH2)2-Z-(CH2)2— or CH2-o-C6H4-Z-CH2—; R8 is H or Me; R9 is selected from R11(CH2)b, R11(CH2)bO and N(R6)(R7); R10 is R11(CH2)b; R11 is selected from H, alkyl, optionally substituted aryl, optionally substituted aroyl, optionally substituted arylsulphonyl and optionally substituted heteroaryl; R12 is selected from H2NCH(R13)CO, H2NCH(R14)CONHCH(R15)CO, C(R16)═C(R17)COR18 and R19OCO; R13, R14 and R15 are selected from the side chains of the proteinaceous amino acids; R16 is selected from H, lower alkyl (C1-C6) and phenyl; R17 is selected from H and lower alkyl (C1-C6); R18 is selected from H, lower alkyl (C1-C6), OH, O-(lower alkyl (C1-C6)) and phenyl; R19 is selected from lower alkyl (C1-C6), optionally substituted phenyl and R20C(=0)OC(R21)(R22); R20, R21 and R22 are each independently selected from H and lower alkyl (C1-C6); Z is selected from a covalent bond, —(CH2)c—, —O—, —SOd— and —N(R10)—; X1 is S or CH2; X2 is O, S or CH2; a is 1, 2 or 3; b is 0-3; c is 1 or 2; and d is 0, 1 or 2.

The present invention relates to novel methods and compositions for detection and isolation of cancer cells with metastatic potential. The invention further relates to assays for measuring the metastatic potential of such cancer cells and drug screening assays for the identification of agents having anti-metastatic potential. The present invention further provides methods and compositions for inhibiting the metastatic potential of cancer cells by modulating the activity of serine integral membrane proteases [(SIMP) consisting of seprase and dipedidyl peptidase IV (DPPIV)]expressed on the surface of metastasizing cancer cells.

The present invention relates to a method of making novel dipeptidyl peptidase-IV ("DPP-IV') inhibitor compounds useful for treating, inter alia, diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes mellitus, metabolic syndrome (Syndrome X or insulin resistance syndrome), hyperglycemia, impaired glucose tolerance, glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome and to prevent disease progression in Type 2 diabetes. The invention also relates to a method of making 3,3,4,4-tetrafluoropyrrolidine, a starting material utilized in the afore-mentioned method for preparing DPP-IV compounds.

The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

A DNA encoding 20K hGH is connected directly to a gene encoding Escherichia coli OppA protein secretion signal, or a modified form thereof, and a DNA encoding signal peptidase 1 to construct a recombinant plasmid, E. coli is transformed by said plasmid and cells of the resulting E. coli transformant strain are cultured for secretory production of the 20K hGH in the E. coli periplasm. This method enables efficient secretory production of 20K hGH and easy isolation and purification of 20K hGH from the periplasm fraction because the level of impure proteins in the E. coli periplasm is low.

The present invention relates to a combination comprising a substance with inhibiting effect on the ileal bile acid transport system (I BAT) and at least one other active substance selected from an IBAT inhibitor; an enteroendocrine peptide or enhancer thereof; a dipeptidyl peptidase-IV inhibitor; a biguanidine; an incretin mimetic; a thiazolidinone; a PPAR agonist; a HMG Co-A reductase inhibitor; a bile acid binder; and a TGR5 receptor modulator; wherein the IBAT inhibitor compound and the at least one other active substance are adminstered simultaneously, sequentially or separately.

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of cancer and conditions involving mitochondrial dysfunction. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1,R2,R3,R4,R5,R6,R7,R8 and R9 are as defined herein.

The invention relates to medicinally used substances which specifically inhibit peptidases splitting Gly-Pro-p-nitroanilide. The invention further relates to the use of at least one such substance or at least one pharmaceutical or cosmetic composition containing at least one such substance for preventing or treating diseases, particularly diseases with an overshooting immune response (autoimmune diseases, allergies, and transplant rejections), other chronic inflammatory diseases, neuronal diseases, brain damages, skin diseases (acne and psoriasis, among others), tumor diseases, and special viral infections (including SARS).

The present disclosure relates to methods for treating bronchiectasis, for example, non-cystic fibrosis bronchiectasis with compositions comprising an effective amount of certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds of Formula (I), including pharmaceutically acceptable salts thereof,that inhibit dipeptidyl peptidase 1 (DPP1) activity. Methods provided herein are useful for prophylaxis, increasing the lung function in a patient, and / or and / or decreasing the rate of pulmonary exacerbation in a patient. In one embodiment, the compound of Formula (I) is (2S)—N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide.

The present invention relates to novel compounds useful as dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula: wherein X, Y, a, R1, and R2 are as defined herein.

Provided is a glucagon-like peptide-1 (GLP-1) analogue shown as the following formula, wherein X is selected from glycine and glycinamide. The GLP-1 analogue has a non-proteogenic amino acid residue in position 8 relative to the sequence GLP-1, and is acylated with a moiety comprising two acidic groups to the lysine residue in position 26. The GLP-1 analogue is resistant to dipeptidyl peptidase IV so as to have an extended half-life in vivo. Also provided is a use of the GLP-1 analogue in conquering blood sugar.