Collagen peptide composition having good ability to enter the blood and food or beverage containing the same

An object of the present invention is to elucidate a collagen peptide effective for causing dipeptides or tripeptides serving as the active component to enter the blood, and thus to reduce the required intake thereof. According to the present invention, a collagen peptide composition obtained by digesting collagen or gelatin with protease is provided, wherein: (a) the ratio of hydroxyproline to total of amino acid residues at the second position from the N terminus of the peptides in the composition is 2 mol % or more and 20 mol % or less, and the ratio of glycine to total of amino acid residues at the third position from the N terminus of the peptides in the composition is 20 mol % or more and 50 mol % or less; and (b) the average molecular weight is 500 or more and 2000 or less.

5,5-FUSED ARYLENE OR HETEROARYLENE HEPATITIS C VIRUS INHIBITORS

Provided herein are 5,5-fused heteroarylene hepatitis C virus inhibitor compounds, for example, of Formula I, IA, or IB, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof. 6. The method of claim 1 , wherein Uis S.7. The method of claim 1 , wherein Wis S.8. The method of claim 1 , wherein Wis O.9. The method of claim 1 , wherein Wis N.10. The method of claim 1 , wherein U claim 1 , W claim 1 , Xand Xare C claim 1 , and Vand Vare each independently CR.17. The method of claim 1 , wherein u is 1.18. The method of claim 1 , wherein u is 2.26. The method of claim 1 , wherein Ris —C(O)R claim 1 , —C(O)CH(NRR)R claim 1 , —C(O)CH[N(C(O)R)R]R claim 1 , —C(O)CH[N(C(O)OR)R]R claim 1 , or —C(O)CH[N(C(O)NRR)R]R.27. The method of claim 26 , wherein Ris —C(O)CH[N(C(O)OR)R]R.28. The method of claim 1 , wherein Ris —C(O)R claim 1 , —C(O)CH(NRR)R claim 1 , —C(O)CH[N(C(O)R)R]R claim 1 , —C(O)CH[N(C(O)OR)R]R claim 1 , or —C(O)CH[N(C(O)NRR)R]R.29. The method of claim 28 , wherein Ris —C(O)CH[N(C(O)OR)R]R.30. The method of claim 3 , wherein each Ris independently hydrogen or —C(O)OR.31. The method of claim 1 , wherein each Ris independently hydrogen claim 1 , methyl claim 1 , isopropyl claim 1 , 2-methylpropyl claim 1 , 1-methylpropyl claim 1 , 2-methylthioethyl claim 1 , phenyl claim 1 , benzyl claim 1 , 3-indolylmethyl claim 1 , hydroxymethyl claim 1 , 1-hydroxyethyl claim 1 , sulfhydrylmethyl claim 1 , 4-hydroxybenzyl claim 1 , aminocarbonylmethyl claim 1 , 2-(aminocarbonyl)ethyl claim 1 , carboxymethyl claim 1 , 2-carboxyethyl claim 1 , 4-aminobutyl claim 1 , 3-guanidinopropyl claim 1 , or 5-imidazolylmethyl.32. The method of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , or butyl.33. The method of claim 1 , wherein Ris hydrogen.34. The method of claim 1 , wherein Rand Rtogether with the C and N atoms to which they ...

NOVEL SELECTIVE INHIBITORS OF PROLYLCARBOXYPEPTIDASE

The present invention relates to compounds of the formulae: 2. A pharmaceutical composition comprising at least one compound according to or an isostere or salt thereof and a pharmaceutically acceptable carrier.3. A method of treating a subject in need of anorexigenic and anti-inflammatory treatment comprising administering to the subject in need of the treatment an effective amount of at least one compound or an isostere or salt thereof according to .4. A method of treating a subject in need of anorexigenic and anti-inflammatory treatment comprising administering to the subject in need of the treatment an effective amount of the pharmaceutical composition according to .5. An anorexigenic and anti-inflammatory composition comprising at least one compound according to or an isostere or salt thereof.6. An anorexigenic and anti-inflammatory pharmaceutical composition comprising at least one compound according to or an isostere or salt thereof and a pharmaceutically acceptable carrier.7. A method of treating obesity comprising administering to a subject in need of the treatment an effective amount of at least one compound according to or an isostere or salt thereof.8. A method of treating obesity comprising administering to the subject in need of the treatment an effective amount of the pharmaceutical composition according to .9. The compound of claim 1 , wherein R is Calkyl.10. The pharmaceutical composition of claim 2 , where R is Calkyl.11. The method of claim 3 , where R is Calkyl.12. The anorexigenic and anti-inflammatory composition of claim 5 , where R is Calkyl.13. The method of treating obesity according to claim 7 , where R is Calkyl. This is a §371 National Stage Application of International Application No. PCT/US2011/062889 filed 1 Dec. 2011 (1 Dec. 2010), pending, which claims priority of U.S. Provisional Application No. 61/418,708 filed 1 Dec. 2010 (1 Dec. 2010), the entire contents of which are incorporated herein by reference in their entirety.This ...

Angiotensin converting enzyme inhibitory peptide

To provide ACE inhibitory peptides which can effectively inhibit ACE by a small amount of ingestion and have no fear of causing side effects and which can be orally ingested easily during daily life by persons having high blood pressure, and compositions comprising the peptides. The peptides represented by the following structural formulae (1) to (9), and salts thereof are provided. (1) Asp-Arg-Pro, (2) Asn-Trp, (3) Val-Gly-Leu, (4) Ile-Gly-Val, (5) Gly-Val-Pro, (6) Ile-Pro-Tyr, (7) pyroGlu-Pro, (8) Tyr-Thr, (9) Pro-Trp

Flavor compositions and screening methods for identifying the same

The presently disclosed subject matter relates to peptides and flavor compositions that include at least one, two, three, four, five or more peptide compounds, and screening methods for identifying the same. The flavor compositions can be used to enhance or modify the taste and/or flavor of various edible compositions such as human food products and pet food products.

BRANCHED CHAIN-CONTAINING AROMATIC COMPOUND

The present invention provides a particular branched chain-containing aromatic compound. The branched chain-containing aromatic compound of the present invention is easily-soluble in isopropyl acetate superior in liquid-separation operability, and can be used for a production method of peptide and the like, which provides a final product simply by extraction separation, without crystallization and isolation of each intermediate in each step. 125-. (canceled)2831-. (canceled) The present invention relates to an aromatic compound containing a particular branched chain. The present invention further relates to a protecting reagent containing the compound or an adduct thereof. The present invention also relates to a production method of peptide by using the compound, and further relates to an organic synthesis method including the production method of the peptide.The production methods of peptide are generally divided into solid phase methods and liquid phase methods. The solid phase methods are advantageous since isolation and purification after reaction can be performed by only washing resin. However, they are associated with problems in that the reaction is essentially that of heterogeneous phases, reaction agents and reagents need to be used in excess to compensate for the low reactivity, and tracing of reaction and analysis of reaction product supported by carrier are difficult. On the other hand, the liquid phase method is advantage since it shows good reactivity, and intermediate peptide can be purified by extraction and washing, isolation and the like after condensation reaction. However, the method is associated with problems since the production step is complicated due to an extraction and washing step with a nonpolar organic solvent and an acidic or basic aqueous solution to remove residual reagents and/or byproducts in each step of coupling reaction and deprotection, and/or an isolation and purification step such as crystallization and the like, and the like ...

FUNCTIONALIZED PEPTIDES AS ANTIVIRAL AGENTS

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof: 2. The compound of wherein A is optionally substituted C-Calkyl.3. The compound of wherein A is optionally substituted heteroaryl.7. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier or excipient.8. A method of treating or preventing a coronavirus infection in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of the compound of . This application is a continuation application of U.S. application Ser. No. 17/379,409, filed on Jul. 19, 2021, which claims the benefit of U.S. Provisional Application No. 63/054,048, filed on Jul. 20, 2020. The entire teachings of the above applications are incorporated herein by reference.The invention relates to compounds and methods of inhibiting coronavirus replication activity by contacting the 3C-Like protease (sometimes referred to as “3CLpro”, “Main protease”, or “Mpro”) with a therapeutically effective amount of a 3C-Like protease inhibitor. The invention further relates to pharmaceutical compositions containing the coronavirus 3C-Like protease inhibitor in a mammal by administering effective amounts of such coronavirus 3C-Like protease inhibitor.Coronaviruses are family of single-stranded, positive-strand RNA viruses with viral envelopes, classified within the Nidovirales order. The coronavirus family comprises pathogens of many animal species, including humans, horses, cattle, pigs, birds, cats and monkeys, and have been known for more than 60 years. The isolation of the prototype murine coronavirus strain JHM, for example, was reported in 1949. Coronaviruses are common viruses that generally cause mild to moderate upper-respiratory tract illnesses in humans, and are named for the crown-like spikes on their envelope surface. There are four major sub-groups known as alpha, beta, gamma and delta coronaviruses, with the ...

Therapeutically active compounds and their methods of use

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.

PREPARATION AND USES OF REACTIVE OXYGEN SPECIES SCAVENGER DERIVATIVES

Compounds of Formula (I)a or (I)b: 2. The method of claim 1 , wherein L is C-Calkyl.3. The method of claim 1 , wherein L is selected from C-Caryl and C-Calkylaryl.4. The method of claim 1 , wherein L is selected from C-Cheteroaryl claim 1 , C-Calkylaryl claim 1 , C-Calkylheteroaryl claim 1 , and pyridine.5. The method of claim 1 , wherein G is absent or G is selected from —NHC(═O)— claim 1 , —NHC(═O)—O— claim 1 , and —NHSO—.8. The method of claim 7 , wherein A is absent or A is valine.9. The method of claim 7 , wherein claim 7 ,{'sup': 1', '1, 'sub': '2', 'Xis absent, or Xis selected from Et-O—C(═O)—, i-Pr—O—C(═O)—, t-Bu-O—C(═O)—, and cyclopropyl-CH—O—C(═O)—;'}{'sup': '2', 'sub': 2', '2', '2', '2, 'Xis selected from i-propyl-CH—, cyclopropyl-CH—, cyclopentyl-CH—, and adamantyl-CH—;'}{'sup': '3', 'sub': 2', '2, 'Xis selected from Ph-CH— and Pyr-CH—; and'}{'sup': '4', 'sub': 2', '2', '2, 'Xis selected from i-propyl-CH—, cyclopropyl-CH—, and cyclopentyl-CH—.'}10. The method of claim 7 , wherein claim 7 ,A is absent;{'sup': '1', 'sub': 2', '2, 'Xis selected from t-Bu-O—C(═O)—, cyclopropyl-CH—O—C(═O)—, and ethyl-CH—O—C(═O)—;'}{'sup': '2', 'sub': '2', 'Xis i-propyl-CH—;'}{'sup': '3', 'sub': '2', 'Xis Ph-CH—; and'}{'sup': '4', 'sub': '2', 'Xis i-propyl-CH—.'}11. The method of claim 7 , wherein claim 7 ,A is absent;{'sup': '1', 'Xis t-Bu-O—C(═O)—;'}{'sup': '2', 'sub': 2', '2, 'Xis selected from i-propyl-CH— and adamantyl-CH—;'}{'sup': '3', 'sub': '2', 'Xis Ph-CH—; and'}{'sup': '4', 'sub': 2', '2', '2, 'Xis selected from cyclopropyl-CH—, cyclopentyl-CH—, and i-propyl-CH—.'}12. The method of claim 7 , wherein.A is valine;{'sup': '1', 'sub': '2', 'Xis selected from t-Bu-O—C(═O)— and cyclopropyl-CH—O—C(═O)—;'}{'sup': '2', 'sub': 2', '2, 'Xis selected from i-propyl-CH— and adamantyl-CH—;'}{'sub': 3', '2, 'Xis Ph-CH—; and'}{'sup': '4', 'sub': 2', '2', '2, 'Xis selected from i-propyl-CH—, cyclopropyl-CH—, and cyclopentyl-CH—.'}14. The method of claim 1 , wherein the administering ...

Nmda receptor modulators and uses thereof

Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

Dimeric IAP Inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language

Functionalized peptides as antiviral agents

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof:which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable slat thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

COMPOUNDS HAVING TRIPLE ACTIVITIES OF THROMBOLYSIS, ANTITHROMBOTIC AND RADICAL SCAVENGING

The present invention relates to a compound simultaneously having triple activities of thrombolysis, antithrombosis and free radical scavenging, as well as the preparation method, composition, and applications thereof. The compound is represented by the formula I shown below: 2. The compound of claim 1 , wherein at least one of the groups for linking is an amino group and the remaining groups for linking are carboxyl groups or amino groups.3. The compound of claim 2 , wherein the linking arm is L-Lys claim 2 , L-Asp claim 2 , or L-Glu.4. The compound of claim 1 , wherein the peptide having thrombolytic activity is selected from a group consisting of an oligopeptide containing a PA (Pro-Ala) sequence claim 1 , a PAK (Pro-Ala-Lys) sequence claim 1 , an AKP (Ala-Lys-Pro) sequence or a KAP (Lys-Ala-Pro) sequence claim 1 , and a peptide having repeated units of the PAK sequence claim 1 , the AKP sequence or the KAP sequence.5. The compound of claim 4 , wherein the oligopeptide having the PA (Pro-Ala) sequence is a tripeptide having the following formula Q1 or Q2:{'br': None, 'Pro-Ala-AA\u2003\u2003(Q1)'}{'br': None, 'AA-Ala-Pro\u2003\u2003(Q2)'}wherein AA is selected from a group consisting of L-Ala, L-Val, L-Trp, L-Tyr, L-Pro, L-Phe, Gly, L-Ser, L-Ile, L-Thr, L-Lys, L-Leu, L-Gln, L-Asn, L-Asp, and L-Glu.6. The compound of claim 1 , wherein Rand Rboth are methyl groups.7. The compound of claim 6 , wherein the linking arm is L-Lys claim 6 , L-Asp claim 6 , or L-Glu claim 6 , and the peptide having thrombolytic activity is a tripeptide having a PA (Pro-Ala) sequence.9. A pharmaceutical composition claim 1 , comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.10. The pharmaceutical composition of claim 9 , wherein the compound is in the form of a nanospherical structure.11. A method for performing thrombolysis claim 9 , NO free radical scavenging or antithrombotic therapy in a subject claim 9 , comprising administrating to the subject an effective ...

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here. 2. The compound of claim 1 , wherein:{'sup': 1', '7, 'sub': 4', '6, 'Ris C-Ccarbocyclyl optionally substituted with one to three Rgroups;'}{'sup': 2', '3', '7, 'each Rand Ris independently selected from aryl or heteroaryl, wherein said aryl or heteroaryl is independently optionally substituted with one to three Rgroups or acrylamido;'}{'sup': 4', '5', '5', '5', '5', '5', '5', '5', '5', '5', '6', '5', '5', '6', '5', '7, 'sub': 2', '1-4', '1', '6', '1-4', '2', '1', '6, 'Ris saturated heterocyclyl, —CH(R)N(R)-heteroaryl, —CH(R)N(R)-aryl, —CH(R)N(R)-heterocyclyl, —CH(R)N(R)-carbocyclyl, heteroaralkyl, —CH-heterocyclyl, 1H-indol-2-yl, indolin-2-yl, 1,2,3,4-tetrahydroquinolin-2-yl, imidazo[1,2-a]pyridine-5-yl, 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-5-yl, —(CRR)N(R)C(O)O(C-Calkyl), or —(CRR)N(R)SO(C-Calkyl), wherein each saturated heterocyclyl, heteroaryl, aryl, heterocyclyl, or carbocyclyl is independently optionally substituted with one to three Rgroups;'}{'sup': '5', 'each Ris independently selected from hydrogen and methyl;'}{'sup': '6', 'sub': 2', '3', '2', '2', '3', '2, 'each Ris independently selected from hydrogen, methyl, CHOH, CH(CH)OH, CHNH, or CH(CH)NH;'}{'sup': 7', '8', '8', '8', '8', '8', '8', '8, 'sub': 3', '2', '3', '3', '2', '1', '3', '2', '2', '2', '2', '2', '1', '3', '1', '3', '2, 'each Ris independently halo, —CF, —CN, —OR, —N(R), —C(O)CH, —C(O)OCH, —SO(C-Calkyl), —C(O)N(R), —O(CH)—OR, SON(R), heteroaryl, —C-Chaloalkyl, C-Calkyl optionally substituted with —ORor —N(R); and'}{'sup': '8', 'sub': 1', '3, 'each Ris independently H or C-Calkyl; and provided that{'sup': '4', '(i) Ris other than thien-2-ylmethyl, 1H-benizimidazol-1-ylmethyl, 1H-indol-3-ylmethyl, or 1H-benzotriazol-1-ylmethyl; and (ii) the compound is not N-[2-[[2-(cyclohexylamino)-1-(3-hydroxyphenyl)-2-oxoethyl] ...

Carbonic anhydrase ix inhibitor conjugates and uses thereof

The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors as therapeutics and imaging agents. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in imaging methods and cancer therapy.

Alpha-Ketoamide Inhibitors Of Cysteine Proteases

The disclosure provides compounds comprising a α-ketoamide linkage that is terminated on each end by an amino acid, such as compounds of Formula (I), wherein RA-RC are defined herein. Also provided are compositions containing these compounds and methods of inhibiting calpain activity, treating a calpain-mediated disorder, inhibiting cathepsin-B, cathepsin-L, cathepsin-S, or cathepsin-L activity, and methods of treating a cathepsin-B, cathepsin-L, cathepsin-S, or cathepsin-L mediated disorder using these compounds and compositions. 1. A compound comprising an α-ketoamide linkage that is terminated on each end by an amino acid.4. The compound of claim 3 , wherein Ris OH or NH.5. The compound of claim 3 , wherein Ris NH(optionally substituted Calkyl) such as NH(methyl) claim 3 , NH(ethyl) claim 3 , NH(propyl) claim 3 , NH(butyl) claim 3 , NH(pentyl) claim 3 , or NH(hexyl) or N(optionally substituted Calkyl)such as N(methyl) claim 3 , N(ethyl) claim 3 , N(propyl) claim 3 , N(butyl) claim 3 , N(pentyl) claim 3 , or N(hexyl).6. The compound of claim 3 , wherein Ris NH(optionally substituted Calkyl-optionally substituted aryl) or NH(optionally substituted Calkyl-optionally substituted heterocyclyl).7. The compound of claim 3 , wherein Ris NH(optionally substituted Calkyl) substituted with C(O)OH claim 3 , C(O)O(Calkyl) claim 3 , or C(O)NH.8. The compound of claim 3 , wherein Ris NH(optionally substituted Ccycloalkyl) such as NH(cyclopentyl).9. The compound of claim 3 , wherein Ris heteroaryl such as pyrrolidinyl or thiazolyl.10. The compound of claim 3 , wherein Ris NH(optionally substituted Calkyl-optionally substituted aryl)C(O)NHsuch as NH(benzyl)C(O)NH.11. The compound of claim 3 , wherein Ris NH-(optionally substituted Calkyl)C(O)NH-(optionally substituted Calkyl-optionally substituted heterocyclyl) such as NH—(Calkyl)C(O)NH—Calkylmorpholinyl.12. The compound of claim 3 , wherein Ris NH-(optionally substituted Calkyl)C(O)NH-optionally substituted Calkyl-optionally ...

CSF1R-BASED CHIMERIC PROTEINS

The present invention relates, in part, to, chimeric proteins which include the extracellular domain of colony stimulating factor 1 receptor (CSF1R) and their use in the treatment of diseases, such as immunotherapies for cancer and/or an inflammatory disease. 1. A heterologous chimeric protein comprising:(a) a first domain comprising a portion of colony stimulating factor 1 receptor (CSF1R) that is capable of binding a CSF1R ligand;(b) a second domain comprising a portion of CD40 Ligand (CD40L) that is capable of binding a CD40L receptor; and(c) a linker linking the first domain and the second domain.2. The heterologous chimeric protein of claim 1 , wherein the first domain comprises substantially all of the extracellular domain of CSF1R and the second domain comprises substantially all of the extracellular domain of CD40L.3. The heterologous chimeric protein of or claim 1 , wherein the chimeric protein is capable of inhibiting an immunosuppressive signal.4. The heterologous chimeric protein of any one of to claim 1 , wherein the chimeric protein is capable of:(a) reducing or eliminating an immune inhibitory signal when the portion of CSF1R is bound to its ligand and/or(b) increasing or activating an immune stimulatory signal when the portion of CD40L is bound to its receptor.5. The heterologous chimeric protein of any one of to claim 1 , wherein the CSF1R ligand is CSF1 or IL-34.6. The heterologous chimeric protein of any one of to claim 1 , wherein the CD40L receptor is CD40.7. The heterologous chimeric protein of any one of to claim 1 , wherein the chimeric protein is capable of contemporaneously binding the CSF1R ligand and the CD40L receptor claim 1 , wherein the CSF1R ligand is CSF1 or IL-34 and the CD40L receptor is CD40.8. The heterologous chimeric protein of any one of to claim 1 , wherein the chimeric protein is capable of contemporaneously binding recombinant human CD40 and human CSF1 in vitro.9. The heterologous chimeric protein of any one of to claim 1 ...

DMSO-FREE CRYOPRESERVATION SOLUTION AND PREPARATION METHOD AND USE THEREOF

A cryopreservation solution contains 0.01-50.0 g of bionic ice control materials, 5.0-30 mL of polyols, 1-30 g of water-soluble sugar, and 0-30 mL of serum, and a buffer in every 100 mL of the cryopreservation solution. It does not contain DMSO. When being used for the cryopreservation of mouse oocytes and embryos, the solution may achieve the same or an even higher cell and tissue survival rate and functional expression stability as or than a commercial cryopreservation solution (containing 15% DMSO), and has high preservation efficiency. The cryopreservation solution without DMSO or serum reduces parasitic biological contaminants in the commercial cryopreservation solution containing serum currently used in clinical practice. 1. A DMSO-free cryopreservation solution , comprising , per 100 mL , 0.01-50 g of a biomimetic ice growth inhibition material , 5.0-45 mL of a polyalcohol , a water-soluble saccharide at 0.1-1.0 mol L , 0-30 mL of serum and the balance of a buffer , wherein the biomimetic ice growth inhibition material is selected from a PVA and/or an amino acid biomimetic ice growth inhibition material.3. The cryopreservation solution according to claim 1 , wherein the ice growth inhibition material is a PVA claim 1 , and the content of the PVA is 0.1-6.0 g;preferably, the polyalcohol may be C2-5 polyalcohol, such as any one of ethylene glycol, propylene glycol and glycerol;preferably, the water-soluble saccharide may be at least one of a non-reducing disaccharide, a water-soluble polysaccharide and a glycoside, for example, selected from sucrose, water-soluble cellulose (e.g., hydroxypropyl methylcellulose), trehalose and polysucrose;preferably, the buffer may be at least one of DPBS, hepes-buffered HTF buffer and other cell buffers;according to the present invention, the serum can be selected from human serum albumin or a substitute thereof, such as sodium dodecyl sulfate, for a human-derived cryopreservation object, and can be fetal bovine serum or bovine ...

TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure. 8. The bifunctional compound according to claim 3 , wherein the chemical linker group (L) is a polyethylenoxy group optionally substituted with aryl or phenyl comprising from 1 to 10 ethylene glycol units.12. The bifunctional compound of claim 1 , wherein the compound is selected from the group consisting of Exemplary Compounds 4 claim 1 , 7-78 claim 1 , 81-88 claim 1 , 93-112 claim 1 , 121-340 claim 1 , 342-392 claim 1 , 394-410 claim 1 , 412-418 claim 1 , 420-481 claim 1 , 483-495 claim 1 , 497-506 claim 1 , 508-523 claim 1 , and 526-547.13. A composition comprising an effective amount of a bifunctional compound of claim 1 , and a pharmaceutically acceptable carrier.14. The composition according to claim 13 , wherein the composition further comprises at least one of additional bioactive agent or another bifunctional compound.15. The composition of claim 14 , wherein the additional bioactive agent is anti-cancer agent.1620.-. (canceled) The present disclosure is a continuation of U.S. patent application Ser. No. 16/744,414, filed ...

DESACETOXYTUBULYSIN H AND ANALOGS THEREOF

In one aspect, the present disclosure provides tubulysin analogs of the formula (I) wherein R, R, R, R, X, X, X, and Aare as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. 5. (canceled)7. (canceled)911-. (canceled)12. The compound of claim 1 , wherein Ris heterocycloalkylor substituted heterocycloalkyl.1314-. (canceled)15. The compound of claim 1 , wherein Ris cycloalkylor substituted cycloalkyl.1639-. (canceled)40. The compound of claim 1 , wherein Ris hydrogen.4147-. (canceled)49. (canceled)50. The compound of claim 48 , wherein Ris aralkylor substituted aralkyl.5159-. (canceled)60. The compound of claim 48 , wherein Ris alkylor substituted alkyl.6162-. (canceled)63. The compound of claim 48 , wherein Ris —COH claim 48 , —C(O)—Ywherein Yis alkoxyor substituted alkoxy claim 48 , or —C(O)—Ywherein Yis an oxygen linked antibody or a nitrogen linked antibody.6467.-. (canceled)68. The compound of claim 1 , wherein Xor Xis —NR— claim 1 , wherein Ris hydrogen claim 1 , alkyl claim 1 , substituted alkyl claim 1 , cycloalkyl claim 1 , or substituted cycloalkyl.6980.-. (canceled)81. The compound of claim 1 , wherein Ais -alkanediyl-heteroarenediyl claim 1 , wherein the alkanediyl is substituted with an amidoor acyloxygroup or a substituted version thereof.8287.-. (canceled)89. (canceled)91. (canceled)93101-. (canceled)103108-. (canceled) This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/120,613, filed on Feb. 25, 2015 and U.S. Provisional Application Ser. No. 62/275,667, filed Jan. 6, 2016, the entire contents of which are hereby incorporated by reference.This disclosure relates to the fields of medicine, pharmacology, chemistry, and oncology. In particular, new compounds, compositions, methods of treatment, and methods ...

TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, inhibitors of apoptosis proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure. 131.-. (canceled)33. The process of claim 32 , wherein the reducing agent is sodium cyanoborohydride.35. The process of claim 34 , wherein the acid is sulfuric acid.37. The process of claim 36 , wherein the coupling is promoted by sodium tert-butoxide claim 36 , palladium acetate claim 36 , and dicyclohexylphosphino-2′ claim 36 ,4′ claim 36 ,6′-triisopropylbiphenyl.39. The process of claim 38 , wherein the base is potassium carbonate.41. The process of claim 40 , wherein the chiral separation is conducted using supercritical fluid chromatography.44. The process of claim 43 , wherein the coupling is promoted by potassium carbonate and (1 claim 43 ,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloride.47. The process of claim 46 , wherein the coupling is promoted by potassium carbonate and (1 claim 46 ,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloride.50. The process of claim 49 , wherein the acid is pyridinium para-toluenesulfonate. This application is a continuation of U.S. application Ser. No. 16/744,414, filed ...

CSF1R-BASED CHIMERIC PROTEINS

The present invention relates, in part, to, chimeric proteins which include the extracellular domain of colony stimulating factor 1 receptor (CSF1R) and their use in the treatment of diseases, such as immunotherapies for cancer and/or an inflammatory disease. 1. A heterologous chimeric protein comprising:(a) a first domain comprising a portion of colony stimulating factor 1 receptor (CSF1R) that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2;(b) a second domain comprising a portion of CD40 Ligand (CD40L) that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4; and(c) a linker linking the first domain and the second domain, the linker comprising a hinqe-CH2-CH3 Fc domain.2. The heterologous chimeric protein of claim 1 , wherein the first domain comprises substantially all of the extracellular domain of CSF1R and the second domain comprises substantially all of the extracellular domain of CD40L.3. (canceled)4. The heterologous chimeric protein of claim 1 , wherein the chimeric protein is capable of:(a) reducing or eliminating an immune inhibitory signal when the portion of CSF1R is bound to its ligand and/or(b) increasing or activating an immune stimulatory signal when the portion of CD40L is bound to its receptor.56-. (canceled)7. The heterologous chimeric protein of claim 1 , wherein the chimeric protein is capable of contemporaneously binding the CSF1R ligand and the CD40L receptor claim 1 , wherein the CSF1R ligand is CSF1 or IL-34 and the CD40L receptor is CD40.810-. (canceled)11. The heterologous chimeric protein of claim 1 , wherein the chimeric protein exhibits enhanced anti-tumor effects compared to CD40 agonist antibodies and/or CSF1R antagonistic antibodies.12. The heterologous chimeric protein of claim 1 , wherein the chimeric protein is capable of increasing or preventing a decrease in a sub-population of CD4 and/or CD8 T cells.13. The heterologous chimeric protein of claim 1 , ...

Process for preparing compounds having triple activities of thrombolysis, antithrombotic and radical scavenging

The present invention relates to a compound simultaneously having triple activities of thrombolysis, antithrombosis and free radical scavenging, as well as the preparation method, composition, and applications thereof. The compound is represented by the formula I shown below: wherein the definitions of T, Q, R 1 and R 2 are described herein. The compound of the present invention simultaneously has triple functions of thrombolysis, free radical scavenging and thrombus-targeting/antithrombosis. The present invention also relates to a pharmaceutical composition comprising the compound, and a preparation method and a nanostructure of the compound.

NDMA RECEPTOR MODULATORS AND USES THEREOF

Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed. 2. The compound of claim 1 , wherein the halogen claim 1 , for each occurrence claim 1 , is independently selected from the group consisting of Cl claim 1 , Br claim 1 , and F.4. The compound of any one of - claim 1 , wherein Xis OH and Xis NH.5. The compound of any one of - claim 1 , wherein each of R claim 1 , R claim 1 , and Ris H.6. The compound of any one of - claim 1 , wherein Rand Ris H claim 1 , and Ris selected from the group consisting of F claim 1 , Br claim 1 , Cl claim 1 , CH claim 1 , CF claim 1 , and —OCH.12. A pharmaceutical composition claim 1 , comprising:{'claim-ref': [{'@idref': 'CLM-00001', 'claims 1'}, {'@idref': 'CLM-00011', '11'}], 'a therapeutically effective amount of a compound of any one of - and a pharmaceutically acceptable carrier.'}13. The pharmaceutical composition of claim 11 , suitable for injection.14. A method of treating depression claim 11 , Alzheimer's disease claim 11 , attention deficit disorder claim 11 , ADHD claim 11 , schizophrenia claim 11 , or anxiety claim 11 , in a patient in need thereof claim 11 , comprising administering to said patient:{'claim-ref': [{'@idref': 'CLM-00001', 'claims 1'}, {'@idref': 'CLM-00012', '12'}], 'a pharmaceutically effective amount of a compound of any one of -.'}15. A method of treating depression claim 11 , Alzheimer's disease claim 11 , attention deficit disorder claim 11 , ADHD claim 11 , schizophrenia claim 11 , or anxiety claim 11 , in a patient in need thereof claim 11 , comprising orally administering to said patient a pharmaceutically ...

Pro-pigmenting peptides

The invention is directed to the use of at least one peptide of formula: X-(Xaa 1 ) n -Pro*-(Xaa 2 ) m -Y (I) With: —n=0, 1 or 2; —m=0 or 1 and if m=0 then n≠0 —Xaa 1 is: —An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; —A polar aminoacid selected from Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q) and analogues and derivatives thereof; —or Glycine (Gly, G); When n=2 the two aminoacids Xaa 1 can be the same or different; —Xaa 2 is: —An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; —A basic aminoacid selected from Arginine (Arg, R), Lysine (Lys, K) and Histidine (His, H) and analogues and derivatives thereof; —Glycine (Gly, G) or Serine (Ser, S); —At the N terminal end of the peptide, X is selected from H, —CO—R 1 and —SO 2 —R 1 ; —At the C terminal end of the peptide, Y is selected from OH, OR 1 , NH 2 , NHR 1 or NR 1 R 2 , R 1 and R 2 being independently from each other, selected from an alkyle, aryle, aralkyle, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulphured, with the possibility to have in said group skeleton a O, S and/or N heteroatom; —Pro* corresponding to a Proline, an analogue or derivative thereof; Excluding the peptides where X=H and Y=OH, for a non therapeutical cosmetic pro-pigmenting treatment of skin. The invention also encompasses new tripeptides of formula (I) suitable for a non therapeutical cosmetic treatment of skin.

TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure. 2. The bifunctional compound according to claim 1 , wherein the E3 ubiquitin ligase binding moiety that targets an E3 ubiquitin ligase selected from the group consisting of Von Hippel-Lindau (VLM) claim 1 , cereblon (CLM) claim 1 , mouse double-minute homolog2 (MLM) claim 1 , and IAP (ILM).7. The bifunctional compound according to claim 1 , wherein the ULM is a cereblon E3 ligase-binding moiety (CLM) selected from the group consisting of a thalidomide claim 1 , lenalidomide claim 1 , pomalidomide claim 1 , analogs thereof claim 1 , isosteres thereof claim 1 , or derivatives thereof.10. The bifunctional compound according to claim 1 , wherein the ULM is a (MDM2) binding moiety (MLM) with a chemical moiety selected from the group consisting of a substituted imidazolines claim 1 , a substituted spiro-indolinones claim 1 , a substituted pyrrolidines claim 1 , a substituted piperidinones claim 1 , a substituted morpholinones claim 1 , a substituted pyrrolopyrimidines claim 1 , a substituted imidazolopyridines claim 1 , a substituted ...

ACYL DIPEPTIDE DERIVATIVE

An acyl dipeptide derivative represented by the formula (1): 2. An acyl dipeptide compound or salt thereof according to claim 1 , wherein R—CO— is a saturated or unsaturated claim 1 , straight or branched chain acyl group having 6 to 14 carbon atoms.3. An acyl dipeptide compound or salt thereof according to claim 1 , wherein R—CO— is a decanoyl group claim 1 , and R claim 1 , Rand Rare all hydrogen atoms.4. A composition claim 1 , comprising at least one acyl dipeptide compound or a salt thereof according to .6. A composition according to claim 5 , wherein R—CO— is a saturated or unsaturated claim 5 , straight or branched chain acyl group having 6 to 14 carbon atoms.7. A composition according to claim 5 , wherein R—CO— is a decanoyl group claim 5 , and R claim 5 , Rand Rare all hydrogen atoms.8. A composition according to claim 5 , which comprises said at least one acyl dipeptide compound or salt thereof (A) in an amount of 0.01 wt % to 40 wt % claim 5 , based on the total weight of said composition.9. A composition according to claim 7 , which comprises said at least one acyl dipeptide compound or salt thereof (A) in an amount of 0.01 wt % to 40 wt % claim 7 , based on the total weight of said composition.10. A composition according to claim 5 , which comprises said at least one acyl proline or salt thereof (B) in an amount of 0.001 wt % to 60 wt % claim 5 , based on the total weight of said composition.11. A composition according to claim 7 , which comprises said at least one acyl proline or salt thereof (B) in an amount of 0.001 wt % to 60 wt % claim 7 , based on the total weight of said composition.12. A composition according to claim 5 , which comprises said at least one acyl dipeptide compound or salt thereof (A) and said at least one acyl proline or salt thereof (B) in a weight ratio (weight of component A/weight of component B) within the range of 100/1-1/1000.13. A composition according to claim 7 , which comprises said at least one acyl dipeptide compound ...

PHARMACEUTICAL COMPOSITION FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASE COMPRISING THE PEPTIDE HAVING THE ABILITY TO INHIBIT ANGIOTENSIN-1 CONVERTING ENZYME AS AN ACTIVE INGREDIENT

The present invention relates to a peptide separated from the fraction of oyster enzyme hydrate displaying the ability of suppressing angiotensin converting enzyme (ACE) and a pharmaceutical composition for the prevention and treatment of cardiovascular disease comprising the said peptide as an active ingredient. Particularly, the peptide separated from the fraction of the oyster enzyme hydrate of the present invention significantly inhibits ACE activity, and thus brings blood pressure regulating effect and antihypertensive effect. Therefore, the fraction of the oyster enzyme hydrate of the invention or the peptide separated from the same can be effectively used as an active ingredient of a pharmaceutical composition for the prevention or treatment of cardiovascular disease. 1. A method for treating cardiovascular disease containing the step of administering at least one of the peptides having the amino acid sequences represented by SEQ ID NOs: 1˜12 to a subject having cardiovascular disease.2. The method according to claim 1 , wherein the peptide is separated from the oyster enzyme hydrate.3. The method according to claim 2 , wherein the enzyme is protease.4. The method according to claim 1 , wherein the peptide inhibiting angiotensin converting enzyme (ACE).5. The method according to claim 1 , wherein the cardiovascular disease is one or more diseases selected from the group consisting of hypertension claim 1 , heart disease claim 1 , stroke claim 1 , thrombosis claim 1 , angina pectoris claim 1 , heart failure claim 1 , myocardial infarction claim 1 , atherosclerosis claim 1 , and arteriosclerosis.6. A method for treating cardiovascular disease containing the step of administering a fraction of the oyster enzyme hydrate containing the peptide comprising one of the amino acid sequences represented by SEQ ID NOs: 1˜NO: 12 to a subject having cardiovascular disease.7. The method according to claim 6 , wherein the fraction is up to 10 kD.8. The method according to ...

PHARMACEUTICAL COMPOSITION FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASE COMPRISING THE PEPTIDE HAVING THE ABILITY TO INHIBIT ANGIOTENSIN-1 CONVERTING ENZYME AS AN ACTIVE INGREDIENT

The present invention relates to a peptide separated from the fraction of oyster enzyme hydrate displaying the ability of suppressing angiotensin converting enzyme (ACE) and a pharmaceutical composition for the prevention and treatment of cardiovascular disease comprising the said peptide as an active ingredient. Particularly, the peptide separated from the fraction of the oyster enzyme hydrate of the present invention significantly inhibits ACE activity, and thus brings blood pressure regulating effect and antihypertensive effect. Therefore, the fraction of the oyster enzyme hydrate of the invention or the peptide separated from the same can be effectively used as an active ingredient of a pharmaceutical composition for the prevention or treatment of cardiovascular disease. 1. A method for treating cardiovascular disease comprising the step of administering a fraction of an oyster enzyme hydrate containing at least one peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1˜2 and SEQ ID NOs. 5˜11 to a subject having cardiovascular disease.2. The method according to claim 1 , wherein the fraction of the oyster enzyme hydrate has a molecular weight up to 10 kD.3. The method according to claim 1 , wherein the cardiovascular disease is one or more diseases selected from the group consisting of hypertension claim 1 , heart disease claim 1 , stroke claim 1 , thrombosis claim 1 , angina pectoris claim 1 , heart failure claim 1 , myocardial infarction claim 1 , atherosclerosis claim 1 , and arteriosclerosis. This application is a divisional of U.S. patent application Ser. No. 14/627,642 filed Feb. 20, 2015, which is a continuation-in-part of PCT/KR2013/007598 filed Aug. 23, 2013 which claims the benefit of Korean patent applications KR-10-2012-0092738 filed Aug. 24, 2012 and KR-10-2013-0100232 filed Aug. 23, 2013, the contents of each of which are incorporated herein by reference in their entirety.The present invention relates to a ...

PROCESS FOR MAKING A 4-AMINO-4-OXOBUTANOYL PEPTIDE CYCLIC ANALOGUE, AN INHIBITOR OF VIRAL REPLICATION, AND INTERMEDIATES THEREOF

The invention provides a process of preparing 4-amino-4-oxobutanoyl peptides and cyclic analogues thereof of Compound I 2. The process of wherein the catalyst to join the ethylene groups is a Grubbs I catalyst claim 1 , a Grubbs II catalyst claim 1 , or a Hoveyda-Grubbs catalyst or a combination of any of the foregoing.5. The process of claim 4 , wherein the strong base is sodium hexamethyldisilazide claim 4 , potassium hexamethyldisilazide claim 4 , lithium hexamethyldisilazide claim 4 , lithium diisopropylamide claim 4 , n-butyllithium claim 4 , or a combination of any of the foregoing.6. The process of claim 5 , wherein the strong base is sodium hexamethyldisilazide.7. The process of claim 4 , wherein the nonenoic acid (19) is formed by reacting 1-bromo-hept-6-ene with an ethoxide salt and a dialkyl malonate in solvent.9. The process of claim 8 , wherein the peptide coupling agent is N claim 8 ,N claim 8 ,N′ claim 8 ,N′-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (TBTU) claim 8 , [Bis(dimethylamino)methylene]-1H-1 claim 8 ,2 claim 8 ,3-triazolo[4 claim 8 ,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) claim 8 , benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) claim 8 , N claim 8 ,N′-Dicyclohexylcarbodiimide (DCC) claim 8 , 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) claim 8 , 2-Chloro-1-methylpyridinium iodide (Mukaiyama's reagent) claim 8 , or a combination of any of the foregoing.10. The process of claim 9 , wherein the peptide coupling agent is N claim 9 ,N claim 9 ,N′ claim 9 ,N′-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (TBTU).11. The process of claim 10 , wherein the protected intermediate is deprotected by reaction with a strong acid.16. The process of claim 15 , wherein R is ethyl claim 15 , ethoxide salt is added to the malonate diester claim 15 , and the solvent is ethanol.17. The process of claim 15 , wherein R is ethyl claim 15 , a strong base is added to the malonate diester claim 15 ...

PREPARATION AND USES OF REACTIVE OXYGEN SPECIES SCAVENGER DERIVATIVES

Compounds of Formula (I)a or (I)b: 2. The compound according to claim 1 , wherein L is C-Calkyl.3. The compound according to claim 1 , wherein L is selected from C-Caryl and C-Calkylaryl.4. The compound according to claim 1 , wherein L is selected from C-Cheteroaryl claim 1 , C-Calkylaryl claim 1 , C-Calkylheteroaryl claim 1 , and pyridine5. The compound according to claim 1 , wherein G is absent or G is selected from —NHC(═O)— claim 1 , —NHC(═O)—O— claim 1 , and —NHSO—.8. The compound according to claim 7 , wherein A is absent or A is valine.9. The compound according to claim 7 , wherein claim 7 ,{'sup': 1', '1, 'sub': '2', 'Xis absent, or Xis selected from Et-O—C(═O)—, i-Pr—O—C(═O)—, t-Bu-O—C(═O)—, and cyclopropyl-CH—O—C(═O)—;'}{'sup': '2', 'sub': 2', '2', '2', '2, 'Xis selected from i-propyl-CH—, cyclopropyl-CH—, cyclopentyl-CH—, and admantyl-CH—;'}{'sup': '3', 'sub': 2', '2, 'Xis selected from Ph-CH— and Pyr-CH—; and'}{'sup': '4', 'sub': 2', '2', '2, 'Xis selected from i-propyl-CH—, cyclopropyl-CH—, and cyclopentyl-CH—.'}10. The compound according to claim 7 , wherein claim 7 ,A is absent;{'sup': '1', 'sub': 2', '2, 'Xis selected from t-Bu-O—C(═O)—, cyclopropyl-CH—O—C(═O)—, and ethyl-CH—O—C(═O)—;'}{'sup': '2', 'sub': '2', 'Xis i-propyl-CH—;'}{'sup': '3', 'sub': '2', 'Xis Ph-CH—; and'}{'sup': '4', 'sub': '2', 'Xis i-propyl-CH—.'}11. The compound according to claim 7 , wherein claim 7 ,A is absent;{'sup': '1', 'Xis t-Bu-O—C(═O)—;'}{'sup': '2', 'sub': 2', '2, 'Xis selected from i-propyl-CH—, and admantyl-CH—;'}{'sup': '3', 'sub': '2', 'Xis Ph-CH—; and'}{'sup': '4', 'sub': 2', '2', '2, 'Xis selected from cyclopropyl-CH—, cyclopentyl-CH—, and i-propyl-CH—.'}12. The compound according to claim 7 , wherein.A is valine;{'sup': '1', 'sub': '2', 'Xis selected from t-Bu-O—C(═O)— and cyclopropyl-CH—O—C(═O)—;'}{'sup': '2', 'sub': 2', '2, 'Xis selected from i-propyl-CH— and admantyl-CH—;'}{'sub': 3', '2, 'Xis Ph-CH—; and'}{'sup': '4', 'sub': 2', '2', '2, 'Xis selected from i- ...

Alkylamine-substituted dicyanopyridine and amino acid ester prodrugs thereof

The present application relates to novel 6-alkylamino-substituted dicyanopyridines, to their amino acid ester prodrugs, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prevention of cardiovascular disorders.

N-ACYLDIPEPTIDE DERIVATIVES AND THEIR USES

N-acyldipeptide derivatives are described. Compositions comprising the N-acyldipeptide derivatives are therapeutically effective for topical or systemic administration to alleviate or improve conditions, disorders, diseases, symptoms or syndromes associated with a tumor, cancer, immune, nervous, vascular, musculoskeletal or cutaneous system, or other tissue or system in a subject. 1. A composition for topical or systemic administration to a mammal comprising a pharmaceutically or cosmetically acceptable carrier and a therapeutically effective amount of a dipeptide derivative having the following generic Formula (I):{'br': None, 'sub': 1', '2, 'R-AAB-AAC-R\u2003\u2003Formula (I)'}or an isomer, free acid, base, salt, lactone, amide, hydrazide, or ester thereof,{'sub': 1', '2', '3', '4', '5', '3', '4', '5', '2', '2', '2', '2', '2, 'wherein Ris an acyl radical having up to 19 carbon atoms; AAB is an amino terminal amino acid residue selected from any amino acid; AAC is a carboxyl terminal amino acid residue selected from any amino acid; Ris OR, NHRor NHNHR; Ris H, an alkyl, aralkyl or aryl radical having up to 19 carbon atoms; Ror Ris independently H, OH, an alkyl, aralkyl, aryl or acyl radical having up to 19 carbon atoms; a side chain of each of AAB and AAC optionally and independently has an extra functional radical selected from the group consisting of OH, SH, NHCONH, NHC(═NH)NH, NH, COOH, CONH, imidazolyl, pyrrolidinyl and indolyl; and the H or OH of the extra functional radical is optionally substituted by NH, an acyl, alkyl, aralkyl, or aryl radical having up to 19 carbon atoms.'}2. The composition of claim 1 , wherein the AAB is an amino terminal amino acid residue selected from the group consisting of Ala claim 1 , βAla claim 1 , Abz claim 1 , Asn claim 1 , Cre claim 1 , Cys claim 1 , Dopa claim 1 , Gly claim 1 , Gln claim 1 , Glu claim 1 , Gaba claim 1 , His claim 1 , Hpg claim 1 , Ile claim 1 , Leu claim 1 , Pgly claim 1 , Phe claim 1 , Pro claim 1 , Ser ...

Chromogenic And Fluorogenic Peptide Substrates For The Detection Of Serine Protease Activity

The present invention relates to chromogenic and fluorogenic substrates that can be used for the highly sensitive and selective detection of the activity of serine proteases. The present invention further relates to methods for the detection of the activity of serine proteases, said methods using the substrates of the present invention. Furthermore, the present invention relates to diagnostic kits and test strips using the above substrates, as well as uses of said substrates.

Hemiasterlin derivatives and uses thereof in the treatment of cancer

The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R 1 -R 7 , X 1 , X 2 , R, Q, and n are as defined herein.

SPIRO RING COMPOUNDS AS HEPATITIS C VIRUS (HCV) INHIBITORS

A compound of formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof is provided, which can be used for treating HCV infection or a HCV disorder. Also a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof are provided, which can also be used for treating HCV infection or a HCV disorder. 2. (canceled)4. (canceled)6. (canceled)810-. (canceled)1415-. (canceled)1718-. (canceled)19. The compound according to claim 1 , wherein each of Y and Y′ is independently a group derived from an α-amino acid and the group derived from the α-amino acid is optionally substituted with one or more substituents claim 1 , wherein the substituent is deuterium claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , hydroxy claim 1 , cyano claim 1 , alkoxycarbonyl claim 1 , aryloxycarbonyl claim 1 , heteroaryloxycarbonyl or heterocyclylcarbonyl; orwherein the α-amino acid is isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophane, valine, alanine, asparagine, aspartic acid, glutamic acid, glutamine, proline, serine, p-tyrosine, arginine, histidine, cysteine, glycine, sarcosine, N,N-dimethylglycine, homoserine, norvaline, norleucine, ornithine, homocysteine, homophenylalanine, phenylglycine, o-tyrosine, m-tyrosine or hydroxyproline; orwherein the α-amino acid is in the D configuration; orwherein the α-amino acid is in the L configuration.2022-. (canceled)23. The compound according to claim 1 , wherein each of Y and Y′ is independently —[U—(CRR)—N(R)—(CRR)]—U—(CRR)—N(R)—(CRR)—R claim 1 , —U—(CRR)—Ror —[U—(CRR)—N(R)—(CRR)]—U—(CRR)—O—(CRR)—R; or{'sup': 9', '9a', '10', '9', '9a', '9', '9a', '11', '9', '9a', '12, 'sub': t', 't', 'k', 't', 't, 'wherein each of Y and Y′ is independently —[U—(CRR)—N(R)—(CRR)]—U—(CRR)—N(R)—(CRR)—R; or'}{'sup': 9', '9a', '10', '9', '9a', '9', '9a', '11', '9', '9a', ...

4-AMINO-4-OXOBUTANOYL PEPTIDES AS INHIBITORS OF VIRAL REPLICATION

The invention provides 4-amino-4-oxobutanoyl peptide compounds of Formula I 2. A compound or salt of claim 1 , wherein{'sub': 1', '2, 'Rand Rare joined to form a 5- to 7-membered heterocyloalkyl ring containing 1 or 2 heteroatoms independently chosen from N, O, and S which ring is optionally fused to a phenyl or 5- or 6-membered heteroaryl to form a bicyclic ring system, each of which 5-to 7-membered heterocycloalkyl ring or bicyclic ring system is optionally substituted.'}3. A compound or salt of claim 2 , wherein{'sub': 1', '2', '2', '1', '2', '1', '2, 'Rand Rare joined to form a pyrrolidine, piperidine, or piperazine ring or a piperazine ring fused to a phenyl, each of which is optionally substituted with 0 to 2 substituents independently chosen from halogen, hydroxyl, amino, CONH, —COOH, C-Calkyl, and C-Calkoxy.'}5. A compound or salt of claim 4 , wherein Ris C-Calkyl or C-Ccycloalkyl.6. A compound or salt of claim 4 , wherein Ris hydrogen.7. A compound or salt of any one of to claim 4 , wherein{'sub': 3', '4, 'claim-text': (a) hydrogen, or', {'sub': 1', '4', '3', '7', '0', '4', '2', '1', '4', '2', '4', '1', '4', '1', '4', '1', '4', '1', '2', '1', '2, '(b) C-Calkyl or (C-Ccycloalkyl)C-Calkyl, each of which is substituted with 0 to 3 substituents independently chosen from halogen, hydroxyl, amino, cyano, —CONH, —COOH, C-Calkyl, C-Calkanoyl, C-Calkoxy, C-Calkylthio, mono- and di-C-Calkylamino, C-Chaloalkyl, and C-Chaloalkoxy.'}], 'Rand Rare independently'}8. A compound or salt of claim 7 , wherein{'sub': 3', '4', '1', '4', '3', '7', '0', '4, 'Rand Rare independently hydrogen, C-Calkyl, or (C-Ccycloalkyl)C-Calkyl.'}9. A compound or salt of claim 8 , wherein{'sub': 3', '4, 'Rand Rare independently hydrogen or methyl.'}10. A compound or salt of any one of to claim 8 , wherein{'sub': 3', '4', '1', '2', '1', '2, 'Rand Rare joined to form a 3- to 7-membered cycloalkyl ring or 3-to 7-membered heterocycloalkyl ring containing 1 or 2 heteroatoms independently chosen from N ...

NMDA RECEPTOR MODULATORS AND USES THEREOF

Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed. 9. A pharmaceutical composition , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a therapeutically effective amount of a compound of and a pharmaceutically acceptable carrier.'}10. The pharmaceutical composition of claim 9 , suitable for oral administration.11. The pharmaceutical composition of claim 9 , suitable for injection.12. A method of treating depression claim 9 , Alzheimer's disease claim 9 , attention deficit disorder claim 9 , ADHD claim 9 , schizophrenia claim 9 , or anxiety claim 9 , in a patient in need thereof claim 9 , comprising administering to said patient:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a pharmaceutically effective amount of a compound of .'} This application claims priority to U.S. Ser. No. 13/525,861, filed Jun. 18, 2012, which claims priority to U.S. Provisional Application No. 61/550,782, filed Oct. 24, 2011, and is a continuation in part of PCT/US 11/24583, filed Feb. 11, 2011, claiming priority to U.S. Provisional Application No. 61/303,472, filed Feb. 11, 2010; all of which are hereby incorporated by reference in their entireties.An N-methyl-d-aspartate (NMDA) receptor is a postsynaptic, ionotropic receptor that is responsive to, inter alia, the excitatory amino acids glutamate and glycine and the synthetic compound NMDA. The NMDA receptor controls the flow of both divalent and monovalent ions into the postsynaptic neural cell through a receptor associated channel (Foster et al., Nature 1987, 329:395-396; Mayer et al., Trends in Pharmacol. Sci. 1990, 11:254-260). ...

N-acyldipeptide Derivatives and Their Uses

Methods of treating aging related skin changes and of increasing skin thickness with topical administration of N-acyldipeptide derivatives are described. Compositions comprising N-acyldipeptide derivatives, are therapeutically effective for increasing skin thickness, and for treating extrinsic and intrinsic aging and aging related skin changes, such as fine lines, wrinkles, photoaging, hyperpigmentation, laxity, age spots, lentigines, mottled skin, and cellulite. 2. The composition of claim 1 , wherein AAB is Tyr and AAC is Tyr.3. The composition of claim 1 , wherein AAB is Val and AAC is Ala.4. The composition of claim 1 , wherein the dipeptide derivative is selected from the group consisting of N—Ac-Tyr-Tyr-NH claim 1 , N—Ac-Tyr-Tyr-OH claim 1 , N—Ac-Tyr-Tyr-OEt claim 1 , N—Ac-Tyr-Tyr-NHNH claim 1 , N—Ac-Tyr-Tyr-NHNHAc claim 1 , N—Ac-Tyr-Tyr-NHOH claim 1 , N—Pr-Tyr-Tyr-NH claim 1 , N—Pr-Tyr-Tyr-OH claim 1 , N—Pr-Tyr-Tyr-OEt claim 1 , N—Pr-Tyr-Tyr-NHNH claim 1 , and N—Pr-Tyr-Tyr-NHNHPr.5. The composition of claim 1 , wherein the dipeptide derivative is selected from the group consisting of N—Ac-Val-Ala-NH claim 1 , N—Ac-Val-Ala-OH claim 1 , N—Ac-Val-Ala-NHOH claim 1 , N—Pr-Val-Ala-NH claim 1 , and N—Pr-Val-Ala-OH.6. The composition of claim 1 , wherein the dipeptide derivative is selected from the group consisting of N—Ac-Tyr-Tyr-NHand N—Ac-Val-Ala-NH.7. The composition of claim 1 , wherein the dipeptide derivative is N—Ac-Val-Ala-NH.8. A method of treating aging related skin changes or changes associated with intrinsic or extrinsic aging claim 1 , or of increasing skin thickness in a subject in need thereof claim 1 , the method comprising topically administering to skin of the subject the composition of .9. The method of claim 8 , wherein the dipeptide derivative is selected from the group consisting of N—Ac-Tyr-Tyr-NH claim 8 , N—Ac-Tyr-Tyr-OH claim 8 , N—Ac-Tyr-Tyr-OEt claim 8 , N—Ac-Tyr-Tyr-NHNH claim 8 , N—Ac-Tyr-Tyr-NHNHAc claim 8 , N—Ac-Tyr-Tyr-NHOH claim 8 ...

TUBULYSIN COMPOUNDS, METHODS OF MAKING AND USE

Tubulysin compounds of the formula (I) 1. A compound having a structure represented by formula (III-13): This application is a continuation of application Ser. No. 15/171,592, filed Jun. 2, 2016; which is a continuation of application Ser. No. 14/605,549, filed Jan. 26, 2015; now U.S. Pat. No. 9,382,289 B2; which is a divisional of application Ser. No. 14/177,376, filed Feb. 11, 2014, now U.S. Pat. No. 8,980,824 B2; which claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 61/764,825, filed Feb. 14, 2013, the disclosures of which are incorporated herein by reference.Incorporated herein by reference in its entirety is a Sequence Listing named “20170407_SEQT_12026USCNT[3]_YC.txt,” comprising SEQ ID NO:1 through SEQ ID NO:26, which include nucleic acid and/or amino acid sequences disclosed herein. The Sequence Listing has been submitted herewith in ASCII text format via EFS-Web, and thus constitutes both the paper and computer readable form thereof. The Sequence Listing was first created using PatentIn 3.5 on Jan. 4, 2014, and is approximately 15 KB in size.This invention relates to compounds structurally similar to the tubulysins, conjugates thereof with a ligand, methods for making and using such compounds and conjugates, and compositions comprising such compounds and conjugates.The tubulysins are cytotoxins originally isolated from cultures of the myxobacteria or , with each organism producing a different mixture of tubulysins (Sasse et al. 2000; Reichenbach et al. 1998). Their crystal structure and biosynthetic pathway have been elucidated (Steinmetz et al. 2004) and their biosynthesis genes have been sequenced (Hoefle et al. 2006b). Pretubulysin, a biosynthetic precursor of the tubulysins, also has been shown to possess some activity (Ullrich et al. 2009). (Full citations for the documents cited herein by first author or inventor and year are listed at the end of this specification.)The tubulysins belong to a group of naturally occurring ...

PRO-PIGMENTING PEPTIDES

The invention is directed to the use of at least one peptide of formula: X-(Xaa)-Pro*-(Xaa)-Y (I) With: —n=0, or 2; —m=0 or land if m=0 then n≠0 —Xaa is: —An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; —A polar aminoacid selected from Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q) and analogues and derivatives thereof; or —Glycine (Gly, G); When n=2 the two aminoacids Xaacan be the same or different; —Xaais: —An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; —A basic aminoacid selected from Arginine (Arg, R), Lysine (Lys, K) and Histidine (His, H) and analogues and derivatives thereof; —Glycine (Gly, G) or Serine (Ser, S); —At the N terminal end of the peptide, X is selected from H, —CO—Rand —SO—R; —At the C terminal end of the peptide, Y is selected from OH, OR, NH, NHRor NRR, —Rand Rbeing independently from each other, selected from an alkyle, aryle, aralkyle, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulphured, with the possibility to have in said group skeleton a O, S and/or N heteroatom; —Pro* corresponding to a Proline, an analogue or derivative thereof; Excluding the peptides where X=H and Y=OH, for a non therapeutical cosmetic pro-pigmenting treatment of skin. The invention also encompasses new tripeptides of formula (I) suitable for a non therapeutical cosmetic treatment of skin. 128.-. (canceled)29. A method for cosmetically pigmenting skin and/or skin appendages of a subject in need thereof comprising topically applying to the skin and/or skin appendages of said subject an ...

N-acyldipeptide derivatives and their uses

N-acyldipeptide derivatives are described. Compositions comprising the N-acyldipeptide derivatives are therapeutically effective for treating disorders and condition associated with the nervous system or musculoskeletal system, such as pain, weakness, numbness, arthritis, joint inflammation, weakness of muscles or joints, and myopia.

Pro-Pigmenting Peptides

The invention is directed to the use of at least one peptide of formula: X-(Xaa)-Pro*-(Xaa)-Y (I) With: -n=0, 1 or 2; -m=0 or 1 and if m=0 then n≠0 -Xaais: -An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; -A polar aminoacid selected from Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q) and analogues and derivatives thereof; -or Glycine (Gly, G); When n=2 the two aminoacids Xaacan be the same or different; -Xaais: -An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; -A basic aminoacid selected from Arginine (Arg, R), Lysine (Lys, K) and Histidine (His, H) and analogues and derivatives thereof; -Glycine (Gly, G) or Serine (Ser, S); -At the N terminal end of the peptide, X is selected from H, —CO—Rand —SO—R; -At the C terminal end of the peptide, Y is selected from OH, OR, NH, NHRor NRR, Rand Rbeing independently from each other, selected from an alkyle, aryle, aralkyle, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulphured, with the possibility to have in said group skeleton a O, S and/or N heteroatom; -Pro* corresponding to a Proline, an analogue or derivative thereof; Excluding the peptides where X=H and Y=OH, for a non therapeutical cosmetic pro-pigmenting treatment of skin. The invention also encompasses new tripeptides of formula (I) suitable for a non therapeutical cosmetic treatment of skin. 1. A dipeptide of formula (I):{'br': None, 'X-(Xaa1)n-Pro*-(Xaa2)m-Y\u2003\u2003(I)'}whereinn=0 and m=1;Xaa2 is selected from the group consisting of Alanine (Ala, A) and Proline (Pro, P);wherein at ...

Therapeutically active compounds and their methods of use

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.

MYOBLAST DIFFERENTIATION PROMOTER

A peptide selected from the group consisting of Ala-Hyp-Gly, Hyp-Gly-Pro, Leu-Hyp, Glu-Hyp, Gly-Pro-Hyp, Pro-Ala, Hyp-Gly and Pro-Hyp, or a pharmaceutically acceptable salt thereof has a myoblast differentiation promoting effect superior to conventional arts. 1. A method for promoting myoblast differentiation promoter comprising administering a peptide selected from the group consisting of Ala-Hyp-Gly , Hyp-Gly-Pro , Leu-Hyp , Glu-Hyp , Gly-Pro-Hyp , Pro-Ala , Hyp-Gly and Pro-Hyp , or a pharmaceutically acceptable salt thereof , to a subject in need thereof.2. The method according to claim 1 , comprising administering a peptide selected from the group consisting of Hyp-Gly and Pro-Hyp claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to a subject in need thereof.3. The method according to claim 1 , comprising administering two or more peptides selected from the group consisting of Ala-Hyp-Gly claim 1 , Hyp-Gly-Pro claim 1 , Leu-Hyp claim 1 , Glu-Hyp claim 1 , Gly-Pro-Hyp claim 1 , Pro-Ala claim 1 , Hyp-Gly and Pro-Hyp claim 1 , or pharmaceutically acceptable salts thereof claim 1 , to a subject in need thereof.4. The method according to claim 1 , wherein the peptide(s) are administered in the form of a preparation for oral administration claim 1 , an injection for direct administration to muscle claim 1 , a transdermal agent claim 1 , a suppository claim 1 , a nasal drop claim 1 , or an inhalant.5. A beverage or food product or a feed claim 1 , comprising a peptide selected from the group consisting of Ala-Hyp-Gly claim 1 , Hyp-Gly-Pro claim 1 , Leu-Hyp claim 1 , Glu-Hyp claim 1 , Gly-Pro-Hyp claim 1 , Pro-Ala claim 1 , Hyp-Gly and Pro-Hyp claim 1 , or a pharmaceutically acceptable salt thereof6. The method according to claim 1 , used for therapy of locomotive syndrome claim 1 , therapy of sarcopenia claim 1 , improvement in the effect of training in athletes claim 1 , students and so on claim 1 , enhancement in physical strength of aged persons ...

Metal Nanostructure and Method for Manufacturing Thereof

The present disclosure relates to a method for manufacturing a metal nanostructure having a chiral structure. The method for manufacturing a metal nanostructure comprises: preparing a first mixture solution by mixing a metal precursor, a surfactant, and a reducing agent; preparing a second mixture solution by adding a peptide to the first mixture solution; and preparing a metal nanostructure having a chiral structure by adding a metal seed particle to the second mixture solution.

PROCESS FOR PREPARATION OF ICATIBANT ACETATE

The invention relates to an improved method for a 5+3+2 solution phase syntheses of Icatibant acetate (1) comprising coupling of suitably protected peptide fragments which on deprotection followed by treatment with acetic acid provide Icatibant acetate (1) having desired purity. 1. A process for the solution phase synthesis of Icatibant acetate (1) , comprising:reacting H Thia-Ser(O-tBu)-D-Tic-Oic-Arg(Pbf)-O-tBu (fragment A) with Fmoc-Hyp-Gly-OH (fragment B) in presence of a coupling agent, in an organic solvent and a base to give a heptapeptide intermediate of the formula, H-Hyp-Gly-Thia-Ser(O-tBu)-D-Tic-Oic-Arg(Pbf)-O-tBu (21),coupling H-Hyp(OP)-Gly-Thia-Ser(OP)-D-Tic-Oic-Arg(Pbf)-O-tBu (21) with Boc-D-Arg(Pbf)-Arg(Pbf)-Pro-OH (fragment C) in presence of a coupling agent, in an organic solvent and a base to provide a decapeptide of the formula Boc-D-Arg(Pbf)-Arg(Pbf)-Pro-Hyp-Gly-Thia-Ser(O-tBu)-D-Tic-Oic-Arg(Pbf)-O-tBu (29), andsubjecting Boc-D-Arg(Pbf)-Arg(Pbf)-Pro-Hyp(O-tBu)-Gly-Thia-Ser(O-tBu)-D-Tic-Oic-Arg(Pbf)-O-tBu (29) to deprotection followed by treatment with acetic acid to provide Icatibant acetate (1) having desired purity.2. (canceled)3. (canceled)4. A process for the solution phase synthesis of Icatibant acetate (1) as claimed in wherein the H-Thia-Ser(O-tBu)-D-Tic-Oic-Arg(Pbf)-OtBu (fragment A) is prepared by:deprotecting Boc-D-Tic-OBn (2) followed by reaction with Boc-Ser(O-tBu)-OH (4) to give Boc-Ser(O-tBu)-D-Tic-OBn (5),deprotecting Boc-Ser(O-tBu)-D-Tic-OBn (5) followed by reaction with H-Oic-OAll (7) or an acid addition salt thereof to afford Boc-Ser-(O-tBu)-D-Tic-Oic-OAll (8),deprotecting Boc-Ser-(O-tBu)-D-Tic-Oic-OAll (8) followed by reaction with Fmoc-Thia-OH (10) to give Fmoc-Thia-Ser(O-tBu)-D-Tic-Oic-OAll (11),deprotecting Fmoc-Thia-Ser(O-tBu)-D-Tic-Oic-OAll (11) followed by reaction with H-Arg(Pbf)-OtBu.HCl (13) to give Fmoc-Thia-Ser(O-tBu)-D-Tic-Oic-Arg(Pbf)-O-tBu (14) which on subsequent deprotection yields fragment A.5. A process for the ...

Dimeric IAP Inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language 2. The compound of claim 1 , comprising a homodimer.3. The compound of claim 1 , wherein the alkyl or optionally-substituted alkyl of R5a and R5b independently is selected from methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , isobutyl claim 1 , sec-butyl claim 1 , tert-butyl claim 1 , cycloalkyl claim 1 , heterocycloalkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , heteroaryl claim 1 , or heteroarylalkyl.4. The compound of claim 1 , wherein R7a and R7b is independently selected from methyl claim 1 , fluoromethyl claim 1 , difluoromethyl claim 1 , ethyl claim 1 , fluoroethyl claim 1 , and cycloalkyl.5. The compound of claim 1 , wherein the optionally substituted alkyl of R5a and R5b is independently selected from alkoxylated and hydroxylated alkyls.6. The compound of claim 1 , wherein R3a and R3b are independently selected from H claim 1 , hydroxy claim 1 , alkyloxy claim 1 , aryloxy claim 1 , alkylamino claim 1 , dialkylamino claim 1 , amido claim 1 , sulfonamido claim 1 , or amidino.7. The compound of claim 1 , wherein when Wa and Wb are covalently bound claim 1 , Wa and Wb together are a bond claim 1 , alkylene claim 1 , alkenylene claim 1 , alkynylene claim 1 , aryl claim 1 , arylalkylene claim 1 , arylalkylalkylene claim 1 , heteroaryl claim 1 , heteroarylalkylene claim 1 , or an ...

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR

The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor. 2. The bifunctional compound of claim 2 , wherein ULM is a hydroxyl prolyl moiety that binds Von Hippel-Lindau (VHL) E3 ubiquitin ligase (VLM).5. The bifunctional compound of claim 3 , wherein VLM is selected from the group consisting of:(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N—((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide;(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(oxazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride;(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methyloxazol-5-yl)benzyl)pyrrolidine-2-carboxamide;(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-N-(4-chlorobenzyl)-4-hydroxypyrrolidine-2-carboxamide hydrochloride;(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-N-(4-cyanobenzyl)-4-hydroxypyrrolidine-2-carboxamide hydrochloride;(2S,4R)-1-((S)-2-amino-3-methylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride;(2S,4R)-1-((S)-2-amino-3-methylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride;(2S,4R)-1-((S)-2-amino-3-methylbutanoyl)-4-hydroxy-N-(4 ...

COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING NEURODEGENERATIVE DISORDERS

Compounds, pharmaceutical compositions, methods and kits are described for treating or preventing neurodegenerative diseases such as Alzheimer's disease. 127-. (canceled)29. A pharmaceutical composition comprising a compound of claim 28 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.30. A method of treating Alzheimer's disease comprising the step of administering to a patient in need thereof a compound of claim 28 , or a pharmaceutically acceptable salt thereof.31. The method of claim 30 , wherein the patient is ApoE4-positive.32. The method of claim 31 , wherein the patient is homozygous for ApoE4. This application is a continuation of U.S. patent application Ser. No. 15/751,547, filed Feb. 9, 2018, which is a U.S. National Phase application, filed under 35 U.S.C. § 371(c) of International Application No. PCT/US2016/046336, filed Aug. 10, 2016, which claims priority to, and the benefit of, U.S. Provisional Application No. 62/203,256, filed Aug. 10, 2015, the disclosure of each of which is hereby incorporated by reference herein in its entirety for all purposes.Alzheimer's disease (AD) is a progressive degenerative disease of the brain primarily associated with aging. Prevalence of AD in the United States in 2000 was close to 4.5 Million. It was estimated that about one in ten individuals over 65 and nearly half of those over 85 are affected by Alzheimer's disease. Approximately 360,000 patients will be diagnosed with AD each year in the United States alone. Clinical presentation of AD is characterized by loss of memory, cognition, reasoning, judgment, and orientation. As the disease progresses, motor, sensory, and linguistic abilities are also affected until there is global impairment of multiple cognitive functions. These cognitive losses occur gradually, but typically lead to severe impairment and eventual death in the range of four to twelve years.Alzheimer's disease is characterized by two major pathologic ...

Prodrugs of carbamate inhibitors of impdh

The present invention relates to carbamate prodrugs of formula (I) that convert to active inhibitors of the IMPDH enzyme of formula (I') in vivo. The compounds and pharmaceutical compositions of this invention are particularly well suited for activation and subsequent inhibition of the IMPDH enzyme activity. Consequently, these prodrugs may be advantageously used as therapeutic agents for IMPDH mediated processes.

New peptide derivatives

The invention relates to new competitive inhibitors of trypsin-like serine proteases, their synthesis, pharmaceutical compositions containing the compounds as active ingredients, and the use of the compounds as thrombin inhibitors, anticoagulants and anti-inflammatory inhibitors for prophylaxis and treatment of related diseases, according to the formulas (I): A1-A2-NH-(CH¿2?)n-B and (V): A?1-A2¿-NH-(CH¿2?)n-B-D wherein A?1¿ represents a structural fragment of formulas (IIa), (IIb), (IIc), (IId), (IIe), A2 represents a structural fragment of formulas (IIIa), (IIIb), (IIIc), B represents a structural fragment of formulas (IVa), (IVb), (IVc), (IVd). Further described are novel compounds, the new use of compounds and especially new structural fragment in synthesis of pharmaceutical compounds.

Novel dipeptide amidines as thrombin inhibitors

The description relates to compounds of formula (I) in which A, B, D, R?1 and R2¿ have the meanings given in the specification. The compounds are suitable for the treatment of diseases. The novel compounds are produced via compounds of the formula H¿2?N-CH2-G-M in which G and M have the meanings given in claim 4.

Antithrombotic agents

This invention relates to thrombin inhibiting compounds having the formula (I): X-Y-NH-(CH2)r-G where X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.

5,5-fused arylene or heteroarylene hepatitis c virus inhibitors

Provided herein are 5,5-fused heteroarylene hepatitis C virus inhibitor compounds, for example, of Formula I, IA, or IB, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof. Formula (I), (IA), (IB).

Aromatic compound containing specific branch

The present invention provides a particular branched chain-containing aromatic compound. The branched chain-containing aromatic compound of the present invention is easily-soluble in isopropyl acetate superior in liquid-separation operability, and can be used for a production method of peptide and the like, which provides a final product simply by extraction separation, without crystallization and isolation of each intermediate in each step.

Template-fixed peptidomimetics with antibacterial activity

Template-fixed β-hairpin peptidomimetics of the general formula (I), wherein Z is a template-fixed chain of 12 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to selectively inhibit the growth of or to kill microorganisms such as Pseudomonas aeruginosa and Acinetobacter. They can be used as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials, or as medicaments to treat or prevent infections. In a specific embodiment, the template is based on the D-Pro-L-Pro dipeptide. These β-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

TUBULYSIS RELATIONSHIPS, METHODS OF PRODUCING AND USING THEREOF

Tubulysin compounds, methods of making and use

Tubulysin compounds of the formula (I) where R 1 , R 2 R 3a , R 3b , R 4 , R 5 , W, and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

Tubulysin compounds, methods of making and use

Tubulysin compounds of the formula (I) where R 1 , R 2 , R 3a , R 3b , R 4 , R 5 , W, and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

Tubulysin compounds, methods of making and use

Tubulysin compounds of the formula (I) where R 1 , R 2 R 3a , R 3b , R 4 , R 5 , W, and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

Tubulysin compounds, methods of making and use

Tubulysin compounds of the formula (I) where R 1 , R 2 R 3a , R 3b , R 4 , R 5 , W, and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

Tubulysin compounds, methods of making and use

Tubulysin compounds of the formula (I) where R 1 , R 2 , R 3a , R 3b , R 4 , R 5 , W, and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

Pyrrolobenzodiazepines and conjugates thereof

Pyrrolobenzodiazepine

Tubulysin compounds, methods of making and use thereof

Tubulysin compounds of the formula (I)where R, R, R, R, R, R, W and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

Dimeric IAP inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of LAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inbhibitors, NSAIDs, taxanes and platinum containing compounds use broader language

Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Compounds and methods for the targeted degradation of androgen receptor

The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor.

Dimeric IAP inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.

Dimeric IAP inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.

Dimeric iap inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language

Dimeric IAP inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.

Dimeric IAP inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language

Dimeric IAP inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.

Dimeric IAP inhibitors

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.

Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, inhibitors of apoptosis proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Novel guanidinyl derivatives

Patent RU2017129429A3

ВУ” 2017129429” АЗ Дата публикации: 17.07.2019 Форма № 18 ИЗ,ПМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2017129429/04(051085) 20.01.2016 РСТД52016/014187 20.01.2016 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [ ] приоритета по первоначальной заявке № из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 62/105,210 20.01.2015 05 Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) СОЕДИНЕНИЯ И СПОСОБЫ ДЛЯ ТАРГЕТНОЙ ДЕГРАДАЦИИ АНДРОГЕНОВОГО РЕЦЕПТОРА Заявитель: АРВИНАС, ИНК., (5 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты (см. Примечания) [ ] приняты во внимание следующие пункты: [ ] принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) (070 417/14 (2006.01) (070 413/14 (2006.01) Аб1Р 35/00 (2006.01) (070 417/12 (2006.01) С07К 5/078 (2006.01) (070 413/12 (2006.01) Аб1К 31/427 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) С07р 417/14 С07О 417/12 С07О 413/12 С07О 413/14 С07К 5/078 Аб1К 31/427 Аб1Р 35/00 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы данных, использованные при поиске (название базы, и если, возможно, поисковые термины): ЕАРАТЬ, РАТЕМТСОРЕ 6. ДОКУМЕНТЫ, ОТНОСЯЩИЕСЯ К ...

Secondary structure stabilized nmda receptor modulators and uses thereof

NMDA 수용체 활성의 조절에서 증진된 효능을 갖는 화합물을 개시한다. 이러한 화합물은 학습, 인지 활동과 같은 질환 및 장애의 치료, 및 진통, 특히 신경병증성 통증의 완화 및/또는 경감에 있어서의 용도를 위해 고려된다. ≪ / RTI > discloses compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders such as learning, cognitive activity, and analgesia, particularly in the alleviation and / or alleviation of neuropathic pain.

Derivatives of tetrahydronaphtalene and tetrahydroisoquinoline as deconstructors of estrogen receptor

FIELD: organic chemistry. SUBSTANCE: invention relates to the field of organic chemistry, particularly to new specific derivatives of tetrahydronaphthalene. Also proposed is a pharmaceutical composition based on specific derivatives of tetrahydronaphthalene for treatment of breast cancer and methods of breast cancer treatment by administration of either the specific derivatives or pharmaceutical compositions based thereon. EFFECT: effective application of tetrahydronaphthalene derivatives as inhibitors of activity of an estrogen receptor. 17 cl, 7 dwg РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 750 484 C2 (51) МПК C07D 401/14 (2006.01) C07D 403/14 (2006.01) A61K 31/496 (2006.01) A61P 35/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 401/14 (2021.02); C07D 403/14 (2021.02); A61K 31/496 (2021.02); A61P 35/00 (2021.02) (21)(22) Заявка: 2020106142, 01.12.2017 (24) Дата начала отсчета срока действия патента: Дата регистрации: 28.06.2021 01.12.2016 US 62/429,041; 01.08.2017 US 62/540,049 Номер и дата приоритета первоначальной заявки, из которой данная заявка выделена: 2019120120 01.08.2017 (43) Дата публикации заявки: 13.04.2020 Бюл. № 11 (73) Патентообладатель(и): ЭРВИНЭС ОПЕРЕЙШНС, ИНК. (US) (56) Список документов, цитированных в отчете о поиске: US 20160045607 A1, 18.02.2016. WO 2016097071, 23.06.2016. US 20160058872 A1, 03.03.2016. RU 2487873 C2, 20.07.2013. EA 19041 B1, 30.12.2013. 2 7 5 0 4 8 4 Приоритет(ы): (30) Конвенционный приоритет: R U 01.12.2017 (72) Автор(ы): КРЮ, Эндрю, П. (US), ЦЯНЬ, Иминь (US), ДУН, Ханьцин (US), ВАН, Цзин (US), ХОРНБЕРГЕР, Кейт, Р. (US), КРЮС, Крэйг, М. (US) C 2 (54) ПРОИЗВОДНЫЕ ТЕТРАГИДРОНАФТАЛИНА И ТЕТРАГИДРОИЗОХИНОЛИНА В КАЧЕСТВЕ РАЗРУШИТЕЛЕЙ ЭСТРОГЕНОВОГО РЕЦЕПТОРА (57) Реферат: Изобретение относится к области путем введения либо конкретных производных, органической химии, в частности к новым либо фармацевтических композиций на их основе. конкретным производным ...

Patent RU2020106142A3

`”ВУ“” 2020106142” АЗ Дата публикации: 07.08.2020 Форма № 18 ИЗИМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2020106142/04(009507) 01.12.2017 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [Х] приоритета 27.06.2019 по первоначальной заявке № 2019120120 из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [ ] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) ПРОИЗВОДНЫЕ ТЕТРАГИДРОНАФТАЛИНА И ТЕТРАГИДРОИЗОХИНОЛИНА В КАЧЕСТВЕ РАЗРУШИТЕЛЕИ ЭСТРОГЕНОВОГО РЕЦЕПТОРА Заявитель: ЭРВИНЭС ОПЕРЕЙШНС, ИНК., 05 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты см. п см. Примечания [ ] приняты во внимание следующие пункты: [ | принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) (0720 417/14 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы данных, использованные при поиске (название базы, и если, возможно, поисковые термины): РУУРТ, Езрасепе, РАТЕМТЗСОРЕ, Рабеагсв, Кеахуз, эТМ ОпПпе, ОЗРТО 6. ДОКУМЕНТЫ, ОТНОСЯЩИЕСЯ К ПРЕДМЕТУ ПОИСКА Кате- Наименование документа с указанием (где необходимо) частей, Относится к гория* относящихся к предмету поиска пункту формулы ...

Hcv/hiv inhibitors an their uses

The present application describes organic compounds of formula (I): that are useful for the treatment, prevention and/or amelioration of human diseases such as HCV and HIV.

Hcv protease inhibitors and uses thereof

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Производные тетрагидронафталина и тетрагидроизохинолина в качестве разрушителей эстрогенового рецептора

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2019 120 120 A (51) МПК C07D 417/14 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2019120120, 01.12.2017 (71) Заявитель(и): ЭРВИНЭС ОПЕРЕЙШНС, ИНК. (US) Приоритет(ы): (30) Конвенционный приоритет: 01.08.2017 US 62/540,049; 01.12.2016 US 62/429,041 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 27.06.2019 US 2017/064283 (01.12.2017) (87) Публикация заявки PCT: WO 2018/102725 (07.06.2018) A Адрес для переписки: 129090, Москва, пр-кт Мира, 6, ООО "Патентно-правовая фирма "ЮС" R U (57) Формула изобретения 1. Бифункциональное соединение, имеющее химическую структуру: ULM-L-РТМ, или его фармацевтически приемлемая соль, энантиомер, стереоизомер, сольват, полиморф или пролекарство, где ULM представляет собой низкомолекулярный фрагмент, связывающий Е3убиквитинлигазу, который связывает Е3-убиквитинлигазу; L представляет собой связь или химический линкерный фрагмент, соединяющий ULM и РТМ; и РТМ представляет собой фрагмент, нацеливающийся на белок, представляющий собой эстрогеновый рецептор, представленный с помощью химической структуры: Стр.: 1 A 2 0 1 9 1 2 0 1 2 0 (54) ПРОИЗВОДНЫЕ ТЕТРАГИДРОНАФТАЛИНА И ТЕТРАГИДРОИЗОХИНОЛИНА В КАЧЕСТВЕ РАЗРУШИТЕЛЕЙ ЭСТРОГЕНОВОГО РЕЦЕПТОРА 2 0 1 9 1 2 0 1 2 0 (86) Заявка PCT: R U (43) Дата публикации заявки: 28.12.2020 Бюл. № 1 (72) Автор(ы): КРЮ, Эндрю, П. (US), ЦЯНЬ, Иминь (US), ДУН, Ханьцин (US), ВАН, Цзин (US), ХОРНБЕРГЕР, Кейт, Р. (US), КРЮС, Крэйг, М. (US) 2 0 1 9 1 2 0 1 2 0 ULM', РТМ' или их комбинации; каждый RPTM1 независимо представляет собой ОН, галоген, алкокси, метокси, этокси, O(CO)RPTM, при этом замещение может предусматривать моно-, ди- или тризамещение, и RPTM представляет собой алкильную или циклоалкильную группу с 1-6 атомами углерода или арильные группы; каждый RPTM2 независимо представляет собой Н, галоген, CN, CF3, линейный или разветвленный алкил, алкокси, метокси, этокси, при этом замещение может ...

Pyrimidine substituted macrocyclic hcv inhibitors

FIELD: medicine, pharmaceutics. SUBSTANCE: there are described new pyrimidine substituted macrocyclic compounds of genral formula (I) , wherein A= -C(=O)OR 1 or -C(=O)-NH-SO 2 -R 2 ; R 1 = H or C 1-6 alkyl; R 2 = phenyl, thienyl, C 3-7 cycloalkyl optionally substituted by C 1-6 alkyl; X = N or CH; E = NR 5 ; R 5 = H or C 1-6 alkyl; n = 4 or 5; R 7 =H, C 1-6 alkyl, C 1-6 alkoxy, phenyl optionally substituted by C 1-6 alkoxy; R 8 =C 1-6 alkoxy, phenyl optionally substituted by C 1-6 alkoxy, morpholino or -NR a R b , wherein R a and R b independently mean H or C 1-6 alkyl; R 9 = R q = H; or their pharmaceutically acceptable addition salts, or stereoisomers, and pharmaceutical compositions containing them. EFFECT: compounds are inhibitors of HCV NS3 serine protease and can find application in treating chronic hepatic disorders, particularly chronic hepatitis. 10 cl, 1 tbl, 25 ex (19) РОССИЙСКАЯ ФЕДЕРАЦИЯ RU (11) 2 481 340 (13) C2 (51) МПК C07D C07D A61K A61P 403/12 (2006.01) 487/04 (2006.01) 31/40 (2006.01) 31/12 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2009133472/04, 08.02.2008 (24) Дата начала отсчета срока действия патента: 08.02.2008 (43) Дата публикации заявки: 20.03.2011 Бюл. № 8 (56) Список документов, цитированных в отчете о поиске: WO 2005/073195 A 11.08.2005. WO 00/59929 A1 12.10.2000. RU 2247126 C2 27.02.2005. (73) Патентообладатель(и): ТИБОТЕК ФАРМАСЬЮТИКАЛЗ ЛТД. (IE), МЕДИВИР АБ (SE) (85) Дата начала рассмотрения заявки PCT на национальной фазе: 08.09.2009 Адрес для переписки: 129090, Москва, ул.Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Е.Е.Назиной, рег.№ 517 (54) ПИРИМИДИН-ЗАМЕЩЕННЫЕ МАКРОЦИКЛИЧЕСКИЕ ИНГИБИТОРЫ HCV (57) Реферат: Описываются новые замещенные макроциклические общей формулы (I) пиримидинсоединения R U 2 4 8 1 3 4 0 (87) Публикация заявки РСТ: WO 2008/095999 (14.08.2008) C 2 C 2 (86) Заявка PCT: EP 2008/051553 (08.02.2008) где Ñòð.: ...

Nmda receptor modulators and uses thereof

NMDA 수용체 활성의 조절에서 증대된 효능을 갖는 화합물이 개시된다. 그와 같은 화합물은 질환 및 장애, 예컨대 학습, 인지 활성, 및 진통의 치료에서, 특히 신경병성 통증의 완화 및/또는 감소시킬 때 사용하기 위해 고려된다. 정맥내 제형을 포함하는, 화합물의 경구로 이용가능한 제형 및 다른 약제학적으로 허용가능한 전달 형태가 또한 개시된다. Compounds having increased efficacy in the regulation of NMDA receptor activity are disclosed. Such compounds are contemplated for use in the treatment of diseases and disorders such as learning, cognitive activity, and analgesia, in particular in the alleviation and / or reduction of neuropathic pain. Also disclosed are orally available formulations of the compounds and other pharmaceutically acceptable forms of delivery, including intravenous formulations.

Nmda receptor modulators and their application

FIELD: pharmacy. SUBSTANCE: compounds are intended for application in treatment of diseases and disorders such as cognitive diseases and disorders, cognitive activity and analgesia, particularly for neuropathic pain relief and/or reduction. . EFFECT: enhanced efficiency of NMDA receptor activity modulation. 12 cl, 16 dwg, 4 tbl, 24 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 621 049 C2 (51) МПК C07K 5/10 (2006.01) A61K 38/07 (2006.01) A61P 25/24 (2006.01) A61P 25/28 (2006.01) A61P 25/18 (2006.01) A61P 25/22 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ФОРМУЛА (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ 2014121090, 24.10.2012 (24) Дата начала отсчета срока действия патента: 24.10.2012 (72) Автор(ы): КХАН Амин М. (US), МОСКАЛ Джозеф (US) (73) Патентообладатель(и): НОРТВЕСТЕРН ЮНИВЕРСИТИ (US) Дата регистрации: (56) Список документов, цитированных в отчете о поиске: EP 2371375 A1, 05.10.2011. US Приоритет(ы): (30) Конвенционный приоритет: 24.10.2011 US 61/550,782 (45) Опубликовано: 31.05.2017 Бюл. № 16 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 26.05.2014 (86) Заявка PCT: US 2012/061696 (24.10.2012) (87) Публикация заявки PCT: 2 6 2 1 0 4 9 (43) Дата публикации заявки: 10.12.2015 Бюл. № 34 6902886 B1, 07.06.2005. US 6897028 B1, 24.05.2005. US 4683221 A, 28.07.1987. US 20050176649 A1, 11.08.2005. JP 3318622 B2, 26.08.2002. WO 2007027559 A2, 08.03.2007. WO 2011044089 A2, 14.04.2011. RU 2011114982 A, 27.10.2012. OHMORI T ET AL, "Isolation of Prolylendopeptidase-Inhibiting Peptides from Bovine Brain", (см. прод.) R U 31.05.2017 (54) МОДУЛЯТОРЫ РЕЦЕПТОРА НМДА И ИХ ПРИМЕНЕНИЕ (57) Формула изобретения 1. Соединение, представленное структурой: R U 2 6 2 1 0 4 9 Адрес для переписки: 191002, Санкт-Петербург, а/я 5, ООО "Ляпунов и партнеры" где Стр.: 1 C 2 C 2 WO 2013/063120 (02.05.2013) R11, R12 и R13, каждый независимо, выбраны из группы, состоящей из Н, галогена, С1-3алкокси и C1-3алкила (необязательно замещенного одним ...

New compounds having triple activities of thrombolysis, antithrombotic and radical scavenging, and synthesis, nano-structure and use thereof

FIELD: chemistry. SUBSTANCE: invention relates to a compound of formula I wherein AA is selected from the group consisting of L-Ala, L-Val, L-Trp, L-Tyr, L-Pro, L-Phe, Gly, L-Ser, L-Ile, L-Thr, L-Lys, L-Leu, L-Gln, L-Asn, L-Asp and L-Glu, simultaneously possessing triple activity in the form of thrombolysis, antithrombosis and free radical scavenging, as well as to the method for preparing the composition. . EFFECT: compounds are intended for the treatment of stroke or cerebral infarction. 7 cl, 9 dwg, 13 tbl, 68 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) (19) RU (11) (13) 2 660 901 C2 (51) МПК C07K 5/037 (2006.01) C07K 5/097 (2006.01) C07D 217/26 (2006.01) A61K 47/55 (2017.01) A61K 38/06 (2006.01) A61P 7/02 (2006.01) A61P 39/06 (2006.01) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07K 5/0215 (2006.01); C07K 5/1024 (2006.01); C07D 217/24 (2006.01); A61K 47/55 (2006.01); A61K 38/06 (2006.01) (21)(22) Заявка: 2015147247, 03.06.2014 03.06.2014 Дата регистрации: 11.07.2018 05.06.2013 CN 201310225330.6 (43) Дата публикации заявки: 05.05.2017 Бюл. № 13 (45) Опубликовано: 11.07.2018 Бюл. № 20 23649 B1, 30.06.2016. CN 101497651 B, 27.06.2012. (85) Дата начала рассмотрения заявки PCT на национальной фазе: 03.11.2015 (86) Заявка PCT: CN 2014/079098 (03.06.2014) C 2 C 2 (56) Список документов, цитированных в отчете о поиске: CN 102241740 A, 16.11.2011. EA (87) Публикация заявки PCT: 2 6 6 0 9 0 1 WO 2014/194809 (11.12.2014) R U 2 6 6 0 9 0 1 (73) Патентообладатель(и): ШАНГХАЙ ЛЮМОСА ТЕРАПЕУТИКС КО., ЭлТэДэ (CN) Приоритет(ы): (30) Конвенционный приоритет: R U (24) Дата начала отсчета срока действия патента: (72) Автор(ы): ПЕН Шики (CN), ЖАО Мин (CN), ВУ Цзяньхуэй (CN), ВАН Юйцзи (CN), ФЭН Цици (CN) Адрес для переписки: 119019, Москва, Гоголевский б-р, 11, этаж 3, "Гоулингз Интернэшнл Инк.", Гизатуллина Евгения Михайловна (54) НОВЫЕ СОЕДИНЕНИЯ, ОБЛАДАЮЩИЕ ТРОЙНОЙ АКТИВНОСТЬЮ, ТРОМБОЛИЗИСНОЙ, АНТИТРОМБОТИЧЕСКОЙ И ЗАХВАТА РАДИКАЛОВ, И ИХ СИНТЕЗ, ...

一种双官能化合物及其制备方法和用途

本发明涉及一种双官能化合物及其制备方法和用途，其中双官能化合物包含结合到E3泛素连接酶结合部分；结合到雄激素受体的靶蛋白结合部分；和将E3泛素连接酶结合部分和靶蛋白结合部分连接的连接部分。本申请双官能化合物使雄激素受体邻近泛素连接酶定位，以实现雄激素受体的降解或抑制。

Производные эналаприл-нитрооксипроизводных и родственные соединения в качестве ингибиторов асе для лечения сердечно-сосудистых заболеваний

ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (11) 2006 100 827 (13) A (51) ÌÏÊ C07D 207/16 (2006.01) ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÇÀßÂÊÀ ÍÀ ÈÇÎÁÐÅÒÅÍÈÅ (21), (22) Çà âêà: 2006100827/04, 11.06.2004 (71) Çà âèòåëü(è): ÍÈÊÎÊÑ Ñ.À. (FR) (30) Êîíâåíöèîííûé ïðèîðèòåò: 19.06.2003 EP 03101796.5 (43) Äàòà ïóáëèêàöèè çà âêè: 27.07.2007 Áþë. ¹ 21 (87) Ïóáëèêàöè PCT: WO 2004/110432 (23.12.2004) Àäðåñ äë ïåðåïèñêè: 121087, Ìîñêâà, à/ 33, ïàò.ïîâ. Â.Â.Êóðûøåâó ÑÎÅÄÈÍÅÍÈß Â ÊÀ×ÅÑÒÂÅ ÈÍÃÈÁÈÒÎÐΠÀÑÅ ÄËß ËÅ×ÅÍÈß ÑÅÐÄÅ×ÍÎ-ÑÎÑÓÄÈÑÒÛÕ ÇÀÁÎËÅÂÀÍÈÉ (57) Ôîðìóëà èçîáðåòåíè 1. Ñîåäèíåíèå îáùåé ôîðìóëû (I) èëè åãî ôàðìàöåâòè÷åñêè ïðèåìëåìà ñîëü èëè ñòåðåîèçîìåð: A ãäå s èìååò çíà÷åíèå 1 èëè 2; À âûáðàí èç ñëåäóþùèõ ãðóïï: ãäå n èìååò çíà÷åíèå îò 1 äî 6, ïðåäïî÷òèòåëüíî ðàâåí 1 èëè 2; N0=-COO- èëè -COOR0, ãäå R0 ïðåäñòàâë åò ñîáîé Í èëè ëèíåéíûé èëè ðàçâåòâëåííûé (C1-C10)-àëêèë; R1 âûáðàí èç ãðóïïû, ñîñòî ùåé èç: R U 2 0 0 6 1 0 0 8 2 7 A (54) ÏÐÎÈÇÂÎÄÍÛÅ ÝÍÀËÀÏÐÈË-ÍÈÒÐÎÎÊÑÈÏÐÎÈÇÂÎÄÍÛÕ È ÐÎÄÑÒÂÅÍÍÛÅ Ñòðàíèöà: 1 RU 2 0 0 6 1 0 0 8 2 7 (86) Çà âêà PCT: EP 2004/051089 (11.06.2004) R U (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 19.01.2006 (72) Àâòîð(û): ÀËÌÈÐÀÍÒÅ Íèêîëåòòà (IT), ÎÍÃÈÍÈ Ýííèî (IT), ÄÅËÜ ÑÎËÄÀÒÎ Ïüåðî (IT) A 2 0 0 6 1 0 0 8 2 7 A 2 0 0 6 1 0 0 8 2 7 R U R U Ñòðàíèöà: 2 A A R2 ìîæåò ïðåäñòàâë òü ñîáîé R U 2 0 0 6 1 0 0 8 2 7 2 0 0 6 1 0 0 8 2 7 ãäå n âë åòñ òàêèì, êàê îïðåäåëåíî âûøå, ïðåäïî÷òèòåëüíî ðàâåí 4; N3 ïðåäñòàâë åò ñîáîé Í èëè R U ãäå N2 èìååò òå æå çíà÷åíè , êîòîðûå îïðåäåëåíû äë N0, è îíè ìîãóò áûòü îäèíàêîâûìè èëè ðàçëè÷íûìè, N2a ïðåäñòàâë åò ñîáîé Í, -Ñ(O)-, -COO, -COOR0, -C(O)R0-, ãäå R0 ïðåäñòàâë åò ñîáîé ëèíåéíûé èëè ðàçâåòâëåííûé (Ñ1-Ñ10)àëêèë; ïðè óñëîâèè, ÷òî ïî ìåíüøåé ìåðå îäíà èç ãðóïï N0, N2 èëè N2a ïðåäñòàâë åò ñîáîé -ÑÎÎ- èëè -Ñ(O)-, òî åñòü îíà èìååò ñâîáîäíóþ âàëåíòíîñòü, ñïîñîáíóþ ê ñâ çûâàíèþ ñ X1; 1b) ãäå N2 ïðåäñòàâë åò ñîáîé -COO-, êîòîðûé èìååò ñâîáîäíóþ âàëåíòíîñòü, ñïîñîáíóþ ê Ñòðàíèöà: 3 ñâ ...

具有溶栓、抗栓和自由基清除三重活性的化合物、其制备方法、组合物和应用

本发明涉及具有溶栓、抗栓和自由基清除三重活性的化合物、其制备方法、组合物和应用。所述化合物为通式I代表： 其中，T、Q、R 1 和R 2 如说明书中所定义。本发明的化合物同时具有溶血栓、清除自由基和血栓靶向/抗血栓三种功能。本发明还涉及包含所述化合物的药物组合物、所述化合物的制备方法以及其纳米结构。

Compounds and compositions as canal activating protease inhibitors

FIELD: medicine, pharmaceutics. ^ SUBSTANCE: present invention refers to compounds of formula ^ , as well as to application of such compounds for preparing a drug which is administered for treatment, relief or prevention of a condition associated with canal activating protease, such as prostasin or trypsin. ^ -J-(R10)p = or . ^ EFFECT: preparing the pharmaceutical compositions which exhibit prostasin or trypsin inhibiting activity. ^ 13 cl, 2 tbl, 53 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 419 625 (13) C2 (51) МПК C07K 5/06 (2006.01) A61K 38/06 (2006.01) A61P 11/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2008150613/04, 15.05.2007 (24) Дата начала отсчета срока действия патента: 15.05.2007 (73) Патентообладатель(и): АЙРМ ЛЛК (BM) 2 4 1 9 6 2 5 (43) Дата публикации заявки: 27.06.2010 Бюл. № 18 2 4 1 9 6 2 5 R U (56) Список документов, цитированных в отчете о поиске: WO 96/40748 A1, 19.12.1996. WO 00/44733 A1, 03.08.2000. WO 2005/023804 A1, 17.03.2005. EP 0291234 A2, 17.11.1988. RU 2181125 C2, 10.04.2002. DONNELLY L E ET AL: "THERAPY FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN THE 21ST CENTURY" DRUGS, 2003, vol.63, no.19, pages 1973-1998. EDWARDS P D ET AL: "DISCOVERY AND BIOLOGICAL ACTIVITY OF ORALLY ACTIVE (см. прод.) (85) Дата начала рассмотрения заявки PCT на национальной фазе: 23.12.2008 (86) Заявка PCT: US 2007/068987 (15.05.2007) (87) Публикация заявки РСТ: WO 2007/140117 (06.12.2007) Адрес для переписки: 101000, Москва, М.Златоустинский пер., 10, кв.15, "ЕВРОМАРКПАТ" (54) СОЕДИНЕНИЯ И КОМПОЗИЦИИ В КАЧЕСТВЕ ИНГИБИТОРОВ ПРОТЕАЗЫ, АКТИВИРУЮЩЕЙ КАНАЛЫ применению таких соединений для изготовления лекарственного средства, которое предназначено для лечения, облегчения или профилактики состояния, связанного с протеазой, активирующей каналы, такой как простазин или трипсин. 6 н. Ñòð.: 1 ru C 2 C 2 (45) Опубликовано: 27.05.2011 Бюл. № 15 (57) Реферат: Настоящее ...

Inhibitors of protease of hepatitis c virus and their application

FIELD: medicine, pharmaceutics. SUBSTANCE: invention relates to compounds, which can be used as inhibitors of protease of hepatitis C virus, pharmaceutical compositions, containing the said compounds, and methods of their application. EFFECT: obtaining compounds which can be used as inhibitors of protease of hepatitis C virus. 41 cl, 10 dwg, 7 tbl, 26 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07K 5/06 C07K 5/08 A61K 38/06 A61K 38/08 A61P 31/14 (13) 2 523 790 C2 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2010125120/04, 19.12.2008 (21)(22) Заявка: (24) Дата начала отсчета срока действия патента: 19.12.2008 Приоритет(ы): (30) Конвенционный приоритет: US US US US 61/016,110; 61/016,473; 61/075,001; 61/098,675 (73) Патентообладатель(и): АВИЛА ТЕРАПЬЮТИКС, ИНК. (US) (45) Опубликовано: 27.07.2014 Бюл. № 21 (56) Список документов, цитированных в отчете о поиске: RU 2298001 С2, 27.04.2007 . WO (85) Дата начала рассмотрения заявки PCT на национальной фазе: 21.07.2010 C 2 C 2 2005037214 A2, 28.04.2005. US 6869964 B2, 22.03.2005. US 2004180815 A1, 16.09.2004 . US 2004162318 A1, 19.08.2004 . US 2003/064499 A1, 03.04.2003. US 2006/121563 A1, 08.06.2006 (86) Заявка PCT: 2 5 2 3 7 9 0 US 2008/087736 (19.12.2008) R U 2 5 2 3 7 9 0 (43) Дата публикации заявки: 27.01.2012 Бюл. № 3 R U 21.12.2007 23.12.2007 23.06.2008 19.09.2008 (72) Автор(ы): НИУ Декианг (US), ПЕТТЕР Рассел (US), СИНГХ Джасвиндер (US), КЛЮГ Артур Ф. (US), КЬЯО Ликсин (US) (87) Публикация заявки PCT: WO 2009/082701 (02.07.2009) Адрес для переписки: 190000, Санкт-Петербург, ул. Малая Морская, 15, офис 5, ВОХ 1125, ООО "ПАТЕНТИКА", М.И.Ниловой (54) ИНГИБИТОРЫ ПРОТЕАЗЫ ВИРУСА ГЕПАТИТА С И ИХ ПРИМЕНЕНИЕ (57) Реферат: Изобретение относится к соединениям, содержат указанные соединения, и способам их которые могут использоваться в качестве применения. 9 н. и 32 з.п. ф-лы, 10 ил., 7 табл., 26 ингибиторов протеазы вируса ...

Procollagen C-proteinase inhibitors

本发明涉及式(Ⅰ)化合物,其中R 1 －R 7 、A、n和Z如发明概述所描述,其为原胶原C端蛋白酶抑制剂,本发明还涉及含有它们的药物组合物,以及它们的应用方法和制备方法。

New dipeptide amidines as thrombin inhibitors

하기 화학식의 화합물이 기재되어 있다. Compounds of the formula are described. 상기 식에서, A, B, D, R 1 및 R 2 는 명세서에 기재된 의미를 갖는다. 상기 화합물은 질환을 억제하는데 적합하다. In the above formula, A, B, D, R 1 and R 2 have the meanings described in the specification. Such compounds are suitable for inhibiting disease. 이 신규 화합물은 하기 화학식의 화합물을 거쳐 제조된다. This new compound is prepared via the following chemical formula. H 2 N-CH 2 -G-M H 2 N-CH 2 -GM 상기 식에서, G 및 M은 청구항 4에 기재된 의미를 갖는다. Wherein G and M have the meanings as defined in claim 4.

Preparation and use of reactive oxygen species scavengers

5,5-condensed arylene or heteroarylene hepatitis c virus inhibitors

FIELD: medicine, pharmaceutics. SUBSTANCE: invention relates to 5,5-condensed heteroarylene compounds IIIB, where U 2 , V 1 , V 2 and W 1 are selected from O, N, NH, S or CR 3a ; U 1 , W 2 , X 1 and X 2 represent C or N; R 1 and R 2 represents hydrogen, -C(O)CH(NR 1b R 1c )R 1a , -C(O)CH(N(R 1c )C(O)OR 1b )R 1a or -C(O)OR 1a ; R 3a represents hydrogen or R 3 ; R 3 represents halogen or -C(O)OR 1a ; L 1 and L 2 are such as given in invention formula, each Z 1 and Z 2 represents bond or -O-; each R la , R 1b and R 1c represents hydrogen, C 1-6 alkyl or C 6-14 aryl; or R lb and R lc together with N atom, which they are bound to, form 5-6-membered heterocyclyl; q, r, s, t and u equal 1. Invention also relates to pharmaceutical compositions, containing 5,5-condensed heteroarylene compounds, and methods of treating or preventing HCV infection. EFFECT: 5,5-condensed heteroarylene derivatives, possessing inhibiting activity with respect to hepatitis C virus. 43 cl, 42 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 554 087 C2 (51) МПК C07D 487/04 (2006.01) C07D 491/048 (2006.01) C07D 495/04 (2006.01) C07D 498/04 (2006.01) C07D 513/04 (2006.01) A61K 31/429 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА A61K 31/424 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ A61K 31/4188 (2006.01) A61P 31/12 (2006.01) (12) ОПИСАНИЕ (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2012130430/04, 17.12.2010 (24) Дата начала отсчета срока действия патента: 17.12.2010 06.08.2010 US 61/371,634; 18.12.2009 US 61/288,207 (45) Опубликовано: 27.06.2015 Бюл. № 18 2006/133326 А1, 14.12.2006. WO 2009/102633 А1, 20.08.2009. WO 2008/144380 А1, 27.11.2008. WO 2008/021928 А2, 21.02.2008. WO 2009/ 102568 А1, 20.08.2009. WO 2007/070556 А2, 21.06.2007. ЕА 200701869 А1, 28.02.2008. RU 2298001 C2, 27.04.2007 (73) Патентообладатель(и): АЙДЕНИКС ФАРМАСЬЮТИКАЛЗ, ИНК. (US) C 2 C 2 (56) Список документов, цитированных в отчете о поиске: WO 2007/070600 А2, 21.06.2007. WO (85) Дата начала рассмотрения заявки PCT на национальной фазе: 18.07.2012 2 5 5 ...

Peptide derivatives, their stereoisomers or physiologically acceptable salts showing antithrombosis, anticoagulating or anti-inflammatory activity, method of their synthesis, pharmaceutical composition, method of suppression of thrombin activity, method of inhibition of kininogenases activity, use of compounds as parent substances for synthesis of thrombin inhibitor

FIELD: organic chemistry, derivatives of peptides. SUBSTANCE: invention relates to peptide derivative of the general formula (I): A 1 -A 2 -NH-(CH) n -D where A 1 is a structural fragment of the formulas (IIa) , (IIb) , (IIc) , (IId) and (IIe) ; k = 0-3; m = 1, 2; q = 0, 1, 2 or 3; R 1 - H, C 1-4 -alkyl, R 11 -OOC-alkyl (other values see p. 1 of the invention claim). Compounds of the formula (I) are effective inhibitors of serine proteases, especially thrombin and kininogenases, for example, kallikrein. EFFECT: improved method of synthesis, enhanced effectiveness of compounds as inhibitors of enzymes. 38 cl, 2 tbl, 91 ex 6 ЭС гс ПЧ Го (19) 13) ВИ ^”2 142 469” Сл 57 МК © 07К 5/00, 5/04, 5/06, 5/08, А 61К 38/04, 38/05, 38/06, 38/55, С 070 239/14, 211/26, С 07 С 257/18, 257/16 РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 96101161/04, 02.06.1994 (71) Заявитель: Астра Актиеболаг (5Е) (24) Дата начала действия патента: 02.06.1994 (72) Изобретатель: Карл Томас Антонссон (3Е), (30) Приоритет: 03.06.1993 ЗЕ 9301916-4 Рут Эльвю Бюлунд ($3Е), Нильс Давид Густафссон ($Е), Нильс Олов Ингемар (46) Дата публикации: 10.12.1999 Нильссон (ЗЕ) — (56) Ссылки: ЗИ 1055096 А, 1985. КЦ 94034734 АЛ, (73) Патентообладатель: © 20.07.96. ЗЦ 1807988 АЗ, 07.04.93. ЕР Астра Актиеболаг (ЗЕ) 0185390 А2, 1986. ЕР 0362002 АЛ, 1990. ЕР 0364344 А2, 1990. ЕР 0293881 А2, 1988. ЕР 0530167 АЛ, 03.03.93. МО 9204371 АЛ, 1992. © ОЕ 2748295 АЛ, 1979. МАРК\МГАКТ ЕРПЕ в а!|. Воспетса! РНАРМАСО! ОСУ\. - 1974, т.23, с. < 2241-2256. < (85) Дата перевода заявки РСТ на национальную |х фазу: 03.01.96 Подробнее