445 results about "Antagonism" patented technology

The present invention provides a novel pyrimidine compound having an excellent adenosine receptor (A1, A2A, A2B receptor) antagonistic action. More specifically, it provides a compound represented by the following formula, a salt thereof or a solvate of them. In the formula, R1 and R2 are the same as or different from each other and each represents a hydrogen atom, an alkyl group having one to six carbon atoms which may be substituted, an alkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a cycloalkenyl group having three to eight carbon atoms which may be substituted, a 5 to 14-membered non-aromatic heterocyclic group which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted, an acyl group having one to six carbon atoms which may be substituted or an alkylsulfonyl group having one to six carbon atoms which may be substituted; R3 represents a hydrogen atom, a halogen atom, a cyano group, an alkyl group having one to six carbon atoms which may be substituted, an alkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted, a nitrogen atom which may be substituted, an oxygen atom which may be substituted or a sulfur atom which may be substituted; R4 represents an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted or a 5 to 14-membered non-aromatic heterocyclic group having at least one or more unsaturated bonds which may be substituted; and R5 represents an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted or a 5 to 14-membered aromatic heterocyclic group which may be substituted.

A compound having excellent adenosine receptor (A1, A2A, A2B receptor) antagonistic action, of the following formula, a salt thereof or a solvate of them:wherein, R1 and R2, same or different, each represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, an aromatic hydrocarbon cyclic group, an acyl group or an alkylsulfonyl group, which groups may be substituted (except the hydrogen atom); R3 represents a hydrogen atom, a halogen atom, a cyano group, an alkyl group, an alkenyl group, an alkynyl group, an aromatic hydrocarbon cyclic group, a nitrogen atom, an oxygen atom or a sulfur atom, which groups may be substituted (except the hydrogen atom, the halogen atom and the cyano group); R4 represents an aromatic hydrocarbon cyclic group which may be substituted, and R5 represents an aromatic hydrocarbon cyclic group which may be substituted.

The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides the necessary information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through one or more metabolic pathways of interest. By this method, a comparison between subjects and control subjects reveals the effects of the chemical entity or entities on the biomarkers. This, in turn, allows for the identification of potential therapeutic uses or toxicities of the compound. Combinations of compounds can also be systematically evaluated for complementary, synergistic, or antagonistic actions on the metabolic pathways of interest, using the methods of the present invention as a strategy for identifying and confirming novel therapeutic or toxic combinations of compounds.

A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and / or prevention of any glucagon-mediated conditions and diseases such as hyperglycemia, Type 1 diabetes, Type 2 diabetes and obesity.

The present invention relates to antagonists of vertebrate growth hormones obtained by mutation of the third alpha helix of such proteins (especially bovine or human GHs). These mutants-have growth-inhibitory or other GH-antagonizing effects. These novel hormones may be administered exogenously to animals, or transgenic animals may be made that express the antagonist. Animals have been made which exhibited a reduced growth phenotype. The invention also describes methods of treating acromegaly, gigantism, cancer, diabetes, vascular eye diseases (diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, retinopathy of sickle-cell anemia, etc.) as well as nephropathy and other diseases, by administering an effective amount of a growth hormone antagonist. The invention also provides pharmaceutical formulations comprising one or more growth hormone antagonists.

The present invention provides a compound represented by the general formula (I) of the present invention, which has EP1 receptor antagonism:wherein A represents a pyridine ring, a furan ring, or the like; Y1 represents a C1-6 alkylene group; Y2 represents a single bond or the like; R1 represents —C(═O)—NH—SO2R6, an acidic 5-membered hetero ring group, or the like; R2 represents an optionally substituted phenyl group, an optionally substituted 5-membered aromatic heterocyclic group, or the like; R3 represents a halogen atom, a C1-6 alkoxy group, or the like; R4 represents a hydrogen atom, a halogen atom, or the like; R5 represents a hydrogen atom or the like; and R6 represents a C1-6 alkyl group or the like], and a pharmaceutically acceptable salt thereof. Furthermore, the compound (I) of the present invention can be used as an agent for treating or preventing LUTS, in particular, various symptoms of OABs.

An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

The present invention relates to a compound represented by the following formula, a pharmacologically acceptable salt thereof, or a use thereof as a pharmaceutical: wherein R1 and R2 are substituents adjacent to each other, and together with two carbon atoms to each of which they attach, form a 5- to 7-membered non-aromatic carbocyclic group or the like, which may be substituted by 1 to 4 substituents selected from (1) an oxo group, (2) a hydroxyl group, and the like; R3 represents a hydrogen atom or the like; and R6 represents a hydrogen atom or the like. It is an object of the present invention to discover an agent for treating or preventing lower urinary tract symptoms, and particularly symptoms regarding urinary storage, which has a superior strength of binding to a 5-HT1A receptor and an antagonism to the receptor.

Disclosed are compounds that are bradykinin B1 receptor antagonists and are useful for treating diseases, or relieving adverse symptoms associated with disease conditions, in mammals mediated by bradykinin B1 receptor.

The present invention is directed to antagonistic antibodies and antigen binding fragments thereof having binding specificity for PACAP. These antibodies inhibit, block or neutralize at least one biological effect associated with PACAP, e.g., vasodilation. In exemplary embodiments these antibodies and antigen binding fragments thereof may comprise specific VH, VL, and CDR polypeptides described herein. In some embodiments these antibodies and antigen binding fragments thereof bind to and / or compete for binding to specific epitope(s) on human PACAP. The invention is further directed to using these antagonistic anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, mast cell degranulation, and / or neuronal activation, are therapeutically beneficial, e.g., headache and migraine indications.

The present invention relates to a thrombin receptor antagonist containing a compound represented by the formula (I)wherein R1a, R1b and R2 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted alkoxy, R3 is a group represented by the formula —NHCOR4, —NHSO2R5, —NHCON(R6a)(R6b), —NHCOOR7 or —CONHR8 wherein R4, R5, R6a, R6b, R7 and R8 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like), ring A is monocyclic aromatic ring optionally further having substituent(s), R1a and R1b are optionally bonded to each other to form an optionally substituted nitrogen-containing non-aromatic heterocycle, or a salt thereof or a prodrug thereof. The thrombin receptor antagonist of the present invention has a thrombin receptor (particularly PAR-1) antagonistic action and is useful for the prophylaxis or treatment of PAR-1 mediated pathological condition or disease.

The instant invention features compounds, for example, 5-HT3 receptor antagonists, having a peripherally restricted mode of action such that the compounds affect 5-HT3 receptors of the peripheral nervous system with diminished or reduced effects in the central nervous system. The compounds are particularly useful in treating disorders or conditions ameliorated by antagonism of peripheral 5-HT3 receptors. Moreover, side-effects attributable to antagonism of central 5-HT3 receptors can be lessened or reduced using the peripherally restricted compounds of the invention.

An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

The invention discloses a compound microbial fertilizer for antagonism of soil-borne fungal diseases, and a preparation method and an application thereof; the fertilizer takes humic acid as a compound carrier, includes bacillus amyloliquefaciens HFJ-7 with the bacteria content of 1.8*10<8>-2.1*10<8> CFU / g, and also includes bacillus megatherium B3. The bacillus amyloliquefaciens HFJ-7 in the compound microbial fertilizer has the preservation number of CGMCC No.10011. The bacillus amyloliquefaciens HFJ-7 strain can be antagonistic to rhizoctonia solani, fusarium oxysporum, root rot pathogen, cucumber fusarium wilt pathogen, phytophthora capsici leon pathogen and other soil-borne disease pathogenic fungi. After the bacillus amyloliquefaciens HFJ-7 is compounded with the bacillus megatherium B3, the resistance to rhizoctonia solani and pepper root rot pathogen can be significantly improved, a disease state index of pepper seedling root rot disease can be significantly reduced, and the occurrence and spreading of pepper root rot can be effectively prevented and controlled.

An antidepressant comprising, as an active ingredient, a compound having an antagonistic effect on group II metabotropic glutamate receptors, as well as a 2-amino-3-alkoxy-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative of Formula [I]:[wherein R1 and R2, which may be the same or different, each represent a hydroxyl group, a C1-10 alkoxy group, etc.; R3 represents a C1-10 acyl group, a C1-6 alkoxy-C1-6 acyl group, etc.; and R4 and R5, which may be the same or different, each represent a hydrogen atom, a C1-10 alkyl group, etc.] or a pharmaceutically acceptable salt or hydrate thereof.

The present invention provides a medicament having a gentle but strong defecation-promoting action without causing diarrhea. That is, it provides a defecation-promoting agent comprising a compound having an adenosine A2 receptor antagonism, preferably an adenosine A2b receptor antagonism, or a salt thereof.

Novel, highly conserved cell cycle regulatory genes (Emg1 and ENIP1) are described along with methods employing Emg1 and ENIP1 to detect compounds that are agonistic or antagonistic to cell cycle progression.

The invention discloses a hypsizygus marmoreus GJ5 strain as well as SSR marker primers and application thereof. The preservation number of the hypsizygus marmoreus GJ5 strain is CCTCC M 2020506; theSSR marker primers comprise five pairs of SSR specific marker primer combinations, and the five pairs of SSR specific marker primers form a fingerprint spectrum. The application comprises the following detection steps: extracting genome DNA of hyphae or sporocarp of a strain to be detected; carrying out SSR molecular marker amplification; carrying out electrophoresis detection; and comparing an electrophoretic band with the fingerprint spectrum, wherein the bacterial strain consistent with the fingerprint spectrum is the hypsizygus marmoreus GJ5 strain. Compared with conventional morphologicaldetection, antagonism experiments and fruiting experiment methods, the SSR fingerprint has the advantages of being short in detection time, high in accuracy, good in repeatability and the like, and the SSR fingerprint constructed through the SSR fingerprint can be used for distinguishing the hypsizygus marmoreus GJ5 strain from 23 main cultivated varieties of hypsizygus marmoreus.

A compound of the formula (I):wherein A is alkylene optionally having an unsaturated bond; R is —C(═O)—R1; R1 is hydroxy or the like; m is 0 or 1; p is 0 or 1; X1 and X3 are each independently optionally substituted aryl or optionally substituted heteroaryl or the like; X2 is a bond, —CH2—, —S—, —SO2—, —CH2—O—, —O—CH2—, —CH2—S—, —S—CH2—, or the like; X4 is —CH2—, —CH2—CH2—, —C(═O)—, or the like, having a dual antagonistic activity against both a thromboxane A2 receptor and a prostaglandin D2 receptor is found.

The invention provides a thio / oxo-naphthalimide compound and application thereof. The compound has a structure shown as a general formula I. The compounds are capable of realizing competitive binding and antagonism of Bcl-2 and Mcl-1 proteins in vitro and in cells so as to induce cell apoptosis, and refer to a type of apoptosis inducers and antitumor compounds with extremely high activities. In addition, the derivative designed based on the compound can serve as a bifunctional molecule and is capable of recognizing, separating, enriching and realizing fluorescence detection of Bcl-2 family proteins; or the derivative can serve as a PROTAC bifunctional complex for selectively degrading the Bcl-2 and Mcl-1 proteins in the cells, so that the level of the Bcl-2 family proteins in living cells is regulated. The structural formula is as shown in the specification.

The present invention provides methods and compositions for drug screens to identify and characterize agents that are agonistic or antagonistic to activation of the promoter region of the NAG-1 gene. Activation of the NAG-1 gene is associated with the apoptotic elimination of cancer cells both in vitro and in vivo. The invention also provides novel promoter region sequences of the NAG-1 gene.

The present invention relates to compounds of Formula (I)as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

The invention discloses a dihydropyrimidine compound as well as a preparation method and an application thereof, and belongs to the technical field of medicinal chemistry. The structure of the dihydropyrimidine compound provided by the invention is as shown in a formula I in the specification. The preparation method provided by the invention comprises the following steps: carrying out substitution reaction on a compound a and a compound k under the catalysis of alkali to generate a compound b; performing substitution reaction on the compound c and the compound d under an alkaline condition to obtain a compound e; carrying out Mitsunobu reaction on the compound e and f to obtain an intermediate g, and carrying out coupling reaction on the compound g and b to generate a compound h. The invention provides the application of the compound shown in the formula I or salt, solvate, allomer, metabolite, nitric oxide and prodrug thereof in preparation of drugs for treating or preventing P2X3 and / or / P2X2 / 3 receptor related diseases. The dihydropyrimidine compound disclosed by the invention has a good P2X3 receptor antagonism effect and better safety.

The invention discloses a dihydropyrimidine compound as well as a preparation method and application thereof, belongs to the technical field of medicinal chemistry, and solves the problems of poor effect and large adverse reaction of a P2X3 receptor inhibitor in the prior art. The structure of the dihydropyrimidine compound is as shown in a formula I in the specification. The invention further provides a preparation method of the compound shown in the formula I and application of the compound in preparation of drugs for treating or preventing P2X3 and / or P2X2 / 3 receptor related diseases. The dihydropyrimidine compound provided by the invention has good affinity with P2X3, has a relatively strong antagonistic effect on a P2X3 receptor, and is safe and effective.

Tetrahydroquinoline derivatives of general formula (I) or salts thereof, having a specific and strong binding affinity for AR and exhibiting AR agonism or antagonism; and pharmaceutical compositions containing the derivatives or the salts.

Disclosed is a novel compound that acts as an antagonist for P2X3 and / or P2X2 / 3 receptors. Also disclosed is a pharmaceutical composition that acts as an antagonist for P2X3 and / or P2X2 / 3 receptors, said composition containing: a compound represented by formula (I), a pharmacologically permitted salt thereof, or a solvate of either. In the formula, ring A represents a substituted or unsubstituted five-to-seven-membered cycloalkane, a substituted or unsubstituted five-to-seven-membered cycloalkene, or the like; C represents a carbon atom; -X- represents -N(R16)- or the like; R16 represents hydrogen, a substituted or unsubstituted alkyl, or the like; R7 represents a substituted or unsubstituted five- or six-membered heteroaryl or a substituted or unsubstituted six-to-ten-membered aryl; each of Q1 and Q2 independently represents a carbon atom or a nitrogen atom; -L- represents -O-, -S-, or the like; R6 represents a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkenyl, or the like; and R2 represents hydrogen, hydroxyl, or the like.

Compounds of the general formula (I): or salts thereof, which exhibit CCR5 antagonism and exert preventive and therapeutic effects against HIV infections: wherein R1 is a 5- to 6-membered aromatic ring which bears a substituent represented by the general formula: R-Z1-X-Z2- (wherein R1 is hydrogen or optionally substituted hydrocarbyl; X is optionally substituted alkylene; and Z1 and Z2 are each a heteroatom) and may be further substituted, with R being optionally bonded to the aromatic ring to form another ring; Y is optionally substituted imino; and R2 and R3 are each optionally substituted aliphatic hydrocarbyl or an optionally Substituted hetero-alicyclic group.

[Problems] Provided is a compound which has an antagonistic action on a muscarinic M3 receptor and is useful as an active ingredient of a prophylactic and / or therapeutic agent for an inflammatory disease such as a chronic obstructive pulmonary disease (COPD), asthma and the like.[Means for Solving Problems] The present inventors have made studies on a compound having an antagonistic action on the binding of a muscarinic M3 receptor, and they have found that an aza-bridged-ring compound or a salt thereof has an antagonistic action on the binding of a muscarinic M3 receptor, thereby completing the present invention. The aza-bridged-ring compound of the present invention has an antagonistic action on the binding of a muscarinic M3 receptor, and can be used as a prophylactic and / or therapeutic agent for an inflammatory disease such as a chronic obstructive pulmonary disease (COPD), asthma and the like.