43 results about "Isostere" patented technology

The present invention provides variants of C-type natriuretic peptide (CNP) comprising one or more deletions; additions of and / or substitutions with natural amino acids, unnatural amino acids and / or peptidomimetics (including peptide bond isosteres); amino acid extensions; and / or other chemical moieties such as, e.g., poly(ethylene glycol) and hydrophobic acids. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders such as, e.g., skeletal dysplasias and achondroplasia, and vascular smooth muscle disorders such as, e.g., restenosis and arteriosclerosis.

This invention provides caspase inhibitors having the formula:wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is hydrogen, CHN2, R, or —CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, an aralkyl group, a heterocyclic group, or an heterocyclylalkyl group; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; Ar is an optionally substituted aryl group; and R3 is hydrogen, an optionally substituted C1-6 alkyl, F2, CN, aryl or R3 is attached to Ar to form an unsaturated or partially saturated five or six membered fused ring having 0–2 heteroatoms. The compounds are useful for treating caspase-mediated diseases in mammals.

The present invention provides variants of C-type natriuretic peptide (CNP) comprising one or more deletions; additions of and / or substitutions with natural amino acids, unnatural amino acids and / or peptidomimetics (including peptide bond isosteres); amino acid extensions; and / or other chemical moieties such as, e.g., poly(ethylene glycol) and hydrophobic acids. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders such as, e.g., skeletal dysplasias and achondroplasia, and vascular smooth muscle disorders such as, e.g., restenosis and arteriosclerosis.

Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined and were used to design substrate analogs of the natural -2 substrate that can inhibit the function of memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. The inhibition constant of OM99-2 is 1.6×10−9 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bound to this inhibitor was used to determine the three dimensional structure of the protein, and the importance of the various residues in binding. This information is useful for designing new inhibitors to memapsin 2, for diagnosing and treating and / or preventing Alzheimer's disease.

Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG. 1). The inhibition constant of OM99-2 is 1.6×10−9 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bound to this inhibitor was used to determine the three dimensional structure of the protein, as well as the importance of the various residues in binding. This information can be used by those skilled in the art to design new inhibitors, using commercially available software programs and techniques familiar to those in organic chemistry and enzymology, to design new inhibitors to memapsin 2, useful in diagnostics and for the treatment and / or prevention of Alzheimer's disease.

A method of forming analogs of CDD-0304, i.e., tetra(ethyleneglycol) (4-methoxy-1,2,5-thiadiazol-3-yl)[3-(1-methyl-1,2,4,5-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl]ether hydrochloride includes one or more of the following steps: a) replacing the tetrahydropyridine moiety with one of the following heterocyclic rings, including quinuclidine, [2.2.1]-exo-azabicy-cloheptane, [2.2.1]-endo-azabicycloheptane and terahydropyrimidine; b) varying the length of the linking group by replacing the tetra(ethylene) glycol moiety with one of: ethylene glycol, di(ethylene) glycol, penta(ethylene) glycol, or diether diol; and / or, c) replacing the 1,2,5-thiadiazole moiety with an ester isostere. Also, a method for an asymmetric analog CCD-0304 includes replacing at least one moiety with an ester isostere and at least a second moiety with an ammonium isostere. Also, such analogs compounds and their uses are disclosed.

The invention discloses application of quinoline derivatives of N-isostere tectorigenin in anti-hepatocarcinoma drugs. The invention relates to the quinoline derivatives of the N-isostere tectorigenin, and the chemical structural formula of the quinoline derivatives is described in the description. The invention provides the application of the quinoline derivatives (new tectorigenin) of the N-isostere tectorigenin in preparation of drugs for inhibiting hepatocelular carcinoma HepG2 cells. The the quinoline derivatives of the N-isostere tectorigenin inhibit the proliferation of the hepatocelular carcinoma HepG2 cells by inhibiting RAF / MEK / ERK pathway and JAK / STAT pathway. The anti-hepatocarcinoma drugs are remarkable in therapeutic effects, and do not easily produce drug resistance and adverse effects. Furthermore, the invention also discloses a higher-yield preparation method of the quinoline derivatives of the N-isostere tectorigenin; the New Tectorigenin is remarkable in effect of inhibiting transplantation tumors.

This invention relates to novel N-linked sulfonamides of N-heterocyclic carboxylic acid and carboxylic acid isosteres, their preparation, and use for treating neurological disorders including physically damaged nerves and neurodegenerative diseases, and for treating alopecia and promoting hair growth.

Information used for creating an adsorption isostere of a substance to be measured in a measuring system (container) is obtained by repeating alternately a first control step of changing temperature or pressure of the measuring system by a fixed amount by adjusting a gas amount supplied to / discharged from the measuring system, and a second control step of changing pressure or temperature of the measuring system by adjusting the gas amount supplied to / discharged from the measuring system until a gas adsorption amount of the substance to be measured becomes the same as before execution of the first control step.

The present invention relates to a compound of formula (I), or a tautomer, stereoisomer, geometrical isomer, prodrug, carboxylic acid isostere, solvate, polymorph, N-oxide, S-oxide or pharmaceutically acceptable salt thereof, which are GPR120 agonists. The present invention also relates to a pharmaceutical composition of a compound of formula (I) for the treatment of metabolic disorders, particularly Type 2 diabetes and associated diseases.

The present invention relates to compounds of the formulae:in which R is C5-C16 alkyl, R1 isand isosteres and salts thereof.

This invention provides caspase inhibitors of formula (I): wherein Z is oxygen or sulfur; R<1> is hydrogen, -CHN2,R, CH2OR, CH2SR, or -CH2Y; Y is an electronegative leaving group; R<2> is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R<3> is a group capable of fitting into the S2 subsite of a caspase enzyme; R<4> and R<5> are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1 beta secretion.