Novel compounds with high therapeutic index

The present invention is directed to novel therapeutic compounds comprised of an amino acid bonded to a medicament or drug having a hydroxy, amino, carboxy or acylating derivative thereon. These high therapeutic index derivatives have the same utility as the drug from which they are made, and they have enhanced pharmacological and pharmaceutical properties. In fact, the novel drug derivatives of the present invention enhance at least one therapeutic quality, as defined herein. The present invention is also directed to pharmaceutical compositions containing same.

Cyclic n,n'-diarylthioureas and n,n'-diarylureas - androgen receptor antagonists, anticancer agent, method for preparation and use thereof

The present invention relates to novel cyclic N,N′-diarylureas and N,N′-diarylthioureas—androgen receptor antagonists, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of cancerous diseases, among them prostate cancer. Cyclic N,N′-diarylthioureas or N,N′-diarylureas of the general formula 1, their optical (R)- and (S)-isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: X represents oxygen or sulfur; m=0 or 1; R1 represents C 1 -C 3 alkyl; R2 and R3 represent hydrogen; or R2 and R3 together with C-atom they are attached to form C═O group; R4 and R5 represent hydrogen; or R4 represents hydrogen, R5 represents methyl; or R4 represents methyl, R5 represents CH 2 R6 group in which R6 represents C 1 -C 3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; or R4 and R5 together with C-atom they are attached to form 5- or 6-membered heterocycle comprising at least one oxygen atom or nitrogen atom optionally substituted with methyl; or R4 and R5 together with C-atom they are attached to form NH group.

Aminodihydrothiazine derivatives

A composition having BACE 1 inhibitory activity containing a compound represented by the general formula (I): wherein ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E is lower alkylene; X is S, O, or NR′; R 1 is a hydrogen atom or lower alkyl; R 2a , R 2b , R 3a , R 3b , R 4a and R 4b is each independently a hydrogen atom, halogen, or hydroxy etc.; n and m are each independently an integer of 0 to 3; n+m is an integer of 0 to 3; R 5 is a hydrogen atom or substituted lower alkyl; its pharmaceutically acceptable salt, or a solvate thereof.

Non-Natural Amino Acids

This invention relates in one aspect to non-natural desamino alkyl amino acid compounds, methods of making these compounds, and peptides containing these compounds. In one embodiment, the peptide is neurotensin (8-13) in which the N-terminus is an alpha-desamino, alpha-methyl-N,N-dimethyl-homolysine residue of the invention. 157-. (canceled)59. The compound of claim 58 , wherein the compound is a compound of Formula (I) and the stereochemistry at Cα is S.60. The compound of claim 58 , wherein the compound is a compound of Formula (I) and R claim 58 , R claim 58 , and Rare independently H or methyl.61. The compound of claim 58 , wherein the compound is a compound of Formula (I) and R is methyl.62. The compound of claim 58 , wherein the compound is:a compound of Formula (I), wherein n is 3, 4 or 5;a compound of Formula (II), wherein n is 2, 3, 4 or 5, and z is 2, 3 or 4;a compound of Formula (III), wherein n is 2, 3, 4 or 5, and z is z is 2, 3 or 4 ora compound of Formula (IV), wherein n is 2, 3 or 4.63. The compound of claim 58 , wherein the compound is selected from the group consisting of compounds 22-43 recited in Scheme 2.64. The compound of claim 58 , wherein the compound is a compound of Formula (I) and the protecting group is BOC (t-butoxy carbonyl) claim 58 , FMOC (fluorenylmethoxycarbonyl) claim 58 , Alloc (allyloxycarbonyl) claim 58 , CBZ (benzyloxycarbonyl) claim 58 , Pbf (2 claim 58 ,2 claim 58 ,4 claim 58 ,6 claim 58 ,7-pentamethyl-dihydrobenzofuran-5-sulfonyl) claim 58 , NO(nitro) claim 58 , Pmc (2 claim 58 ,2 claim 58 ,5 claim 58 ,7 claim 58 ,8-pentamethylchroman-6-sulfonyl) claim 58 , Mtr (4-methoxy-2 claim 58 ,3 claim 58 ,6-trimethylbenzenesulfonyl) claim 58 , or Tos (tosyl).66. The peptide of claim 65 , wherein the peptide is a known peptide claim 65 , further wherein the residue is covalently coupled through an amide bond to the N-terminus amine group of the known peptide claim 65 , a substitute for its corresponding analogous natural amino acid ...

PROCESS FOR PREPARING ANTIVIRAL COMPOUNDS

This disclosure is directed to: (a) processes for preparing compounds and salts thereof that, inter alia, are useful for inhibiting hepatitis C virus (HCV); (b) intermediates useful for the preparation of the compounds and salts; (c) pharmaceutical compositions comprising the compounds or salts; and (d) methods of use of such compositions. 2. The process of claim 1 , wherein LGis selected from the group consisting of chloro claim 1 , bromo claim 1 , iodo and —OSOR claim 1 , wherein Ris selected from the group consisting of aryl claim 1 , alkyl claim 1 , fluoroalkyl claim 1 , -fluoroalkyl-O-fluoroalkyl claim 1 , —N(alkyl) claim 1 , —O(alkyl) claim 1 , —O(aryl) claim 1 , fluoro claim 1 , imidazolyl claim 1 , and isomers and homologs thereof.3. The process of claim 1 , wherein Ris t-butyl claim 1 , Ris methoxy claim 1 , and Ris methyl.4. The process of claim 2 , wherein Ris CF.5. The process of claim 2 , wherein Ris perfluorobutyl or trifluoromethyl.6. The process of wherein compound (5) is 6-(3-tert-butyl-5-(2 claim 1 ,4-dioxo-3 claim 1 ,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl 1 claim 1 ,1 claim 1 ,2 claim 1 ,2 claim 1 ,3 claim 1 ,3 claim 1 ,4 claim 1 ,4 claim 1 ,4-nonafluorobutane-1-sulfonate.7. The process of claim 1 , wherein compound (5) is sulfonamidated using a transition metal catalyst or transition metal catalyst precursor and ligand in the presence of a base and a solvent.8. The process of claim 7 , wherein the transition metal in the transition metal catalyst or transition metal catalyst precursor is palladium.9. The process of claim 8 , wherein the palladium catalyst or palladium catalyst precursor is selected from the group consisting of tetrakis(triphenylphosphine)palladium(0) claim 8 , dichlorobis(tri-o-tolylphosphine)palladium(II) claim 8 , palladium(II) acetate claim 8 , [1 claim 8 ,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) claim 8 , tris(dibenzylideneacetone)dipalladium(0) claim 8 , bis(dibenzylideneacetone) ...

CYCLIC UREA INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1

This invention relates to novel compounds of the Formula (I), (Ia) and (Ib), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, j which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell Or the inhibition of the conversion of cortisone to Cortisol in a cell. 2. The compound of wherein claim 1 ,{'sup': 1a', '1b, 'sub': 1', '6', '2', '6', '2', '6', '1', '3', '1', '3', '1', '3', '2, 'Rand Rare each independently (a) hydrogen or (b) (C-C)alkyl, (C-C)alkenyl, (C-C)alkynyl or (C-C)alkoxy(C-C)alkyl, each of which are optionally substituted with up to three groups independently selected from fluorine, hydroxy, (C-C)alkoxy and HNC(═O);'}{'sub': 1', '8', '2', '8', '2', '8', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'sup': 4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4, 'A is straight or branched (C-C)alkyl, (C-C)alkenyl or (C-C)alkynyl, each of which are optionally substituted with up to 4 groups independently selected from fluorine, cyano, oxo, R, RO—, (R)N—, ROC—, RS, RS(═O)—, RS(═O)—, RC(═O)NR—, (R)NC(═O)—, (R)NC(═O)O—, (R)NC(═O)NR—, ROC(═O)NR—, (R)NC(═NCN)NR—, (RO)P(═O)O, (RO)P(═O)NR—, ROS(═O)NR—, (R)NS(═O)O—, (R)NS(═O)NR—, RS(═O)NR—, RS(═O)NHC(═O)—, RS(═O)NHC(═O)O—, RS(═O)NHC(═O)NR—, ROS(═O)NHC(═O)—, ROS(═O)NHC(═O)O—, ROS(═O)NHC(═O)NR—, (R)NS(═O)NHC(═O)—, (R)NS(═O)NHC(═O)O—, (R)NS(═O)NHC(═O)NR—, RC(═O)NHS(═O)—, RC(═O)NHS(═O ...

Novel pharmaceutical compounds

Novel compounds and pharmaceutical compositions are provided. In one aspect of the invention the compounds may be utilized in medical practice, for example, in treatment of cancer and immune disorders.

3,5 Phenyl-Substituted Beta Amino Acid Derivatives as Integrin Antagonists

Disclosed herein are novel pharmaceutical agents which are useful as integrin receptor antagonists that mediate the pathologic processes of angiogenesis and fibrosis and as such are useful in pharmaceutical compositions and in methods for treating conditions mediated by these integrins by inhibiting or antagonizing these integrins. The novel pharmaceutical agents include those of the formula: 4. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) the compound of ; and'}b) an excipient.5. A method of treating and/or preventing a disease or a disorder in a patient in need thereof claim 1 , comprising administering to the patient a compound of in an amount sufficient to treat and/or prevent the disease or disorder.6. The method of claim 5 , wherein the disease or disorder is associated with angiogenesis.7. The method of claim 5 , wherein the disease or disorder is associated with fibrosis.8. (canceled)9. The method of claim 5 , wherein the disease or disorder is pulmonary claim 5 , liver claim 5 , renal claim 5 , cardiac claim 5 , and pancreatic fibrosis claim 5 , scleroderma claim 5 , scarring claim 5 , retinopathy of prematurity claim 5 , familial exudative vitreoretinopathy claim 5 , proliferative vitreoretinopathies claim 5 , macular degeneration claim 5 , diabetic retinopathy claim 5 , cancer claim 5 , osteoporosis claim 5 , autoimmune diseases claim 5 , humoral hypercalcemia of malignancy claim 5 , Paget's disease claim 5 , periodontal disease claim 5 , psoriasis claim 5 , arthritis claim 5 , restenosis claim 5 , and infection.1015.-. (canceled)16. The method of claim 9 , wherein the disease or disorder is scarring.17. The method of claim 16 , wherein the scarring is dermal scarring.1824.-. (canceled)25. The method of claim 9 , wherein the disease or disorder is cancer.2630.-. (canceled)31. The method of claim 9 , wherein the disease or disorder is an autoimmune disease.32. The method of claim 31 , wherein the autoimmune ...

HYDROXAMIC ACID DERIVATIVES

The present invention is directed to a method of alleviating, relieving, altering, remedying, ameliorating, improving or affecting a neoplastic disease or an immune disease, the method comprising administering to a subject in need thereof an effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof: 2. A method of alleviating , relieving , altering , remedying , ameliorating , improving or affecting a neoplastic disease or an immune disease according to , the method comprising administering to a subject in need thereof an effective amount of a compound or salt of , wherein Z is deleted , CH , O , CO , NH , SO , OC(O) , C(O)O , C(O)S , NHC(O) , C(O)NH , OC(O)NH , NHC(O)O , or NHC(O)S; m is 5 , 6 , 7 , or 8.3. A method of alleviating , relieving , altering , remedying , ameliorating , improving or affecting a neoplastic disease or an immune disease according to , the method comprising administering to a subject in need thereof an effective amount of a compound or salt of , wherein Q is an aryl or heteroaryl.4. A method of alleviating , relieving , altering , remedying , ameliorating , improving or affecting a neoplastic disease or an immune disease according to , the method comprising administering to a subject in need thereof an effective amount of a compound or salt of , wherein Q is a 9-10 membered aryl or heteroaryl.8. A method of alleviating claim 1 , relieving claim 1 , altering claim 1 , remedying claim 1 , ameliorating claim 1 , improving or affecting a neoplastic disease according to claim 1 , wherein said neoplastic disease is selected from the group consisting of lung cancer claim 1 , head and neck cancer claim 1 , central nervous system cancer claim 1 , prostate cancer claim 1 , testicular cancer claim 1 , colorectal cancer claim 1 , pancreatic cancer claim 1 , liver cancer claim 1 , stomach cancer claim 1 , biliary tract cancer claim 1 , esophageal cancer claim 1 , gastrointestinal stromal tumor claim 1 , breast cancer ...

USE OF 3-CARBOXY-N-ETHYL-N,N-DIMETHYLPROPAN-1-AMINIUM SALTS IN THE TREATMENT OF CARDIOVASCULAR DISEASE

Salts of 3-carboxy-N-ethyl-N,N-dimethylpropan-1-aminium, method of preparation thereof and use in the treatment of cardiovascular disease. 19-. (canceled)14. A process for preparing the 3-carboxy-N-ethyl-N claim 10 ,N-dimethylpropan-1-aminium salt according to claim 10 , comprising:a. adding N,N-dimethylethylamine to ethyl 4-bromobutanoate in appropriate solvent to obtain 4-ethoxy-N-ethyl-N,N-dimethyl-4-oxo-1-butanaminium bromide;b. passing 4-ethoxy-N-ethyl-N,N-dimethyl-4-oxo-1-butanaminium bromide through ion exchange resin column to obtain 4-[ethyl(dimethyl)ammonio] butanoate;c. adding acid selected from the group, consisting of fumaric acid, orotic acid and phosphoric acid in appropriate solvent to obtain the corresponding 3-carboxy-N-ethyl-N,N-dimethylpropan-1-aminium salt.15. The process according to claim 14 , wherein in step a) the appropriate solvent is acetonitrile or acetone.16. A method for treating cardiovascular diseases in a subject in need thereof claim 10 , comprising administration of an effective amount of the 3-carboxy-N-ethyl-N claim 10 ,N-dimethylpropan-1-aminium salt of .17. The method according to claim 16 , wherein the cardiovascular disease is ischemic heart disease.18. The method according to claim 16 , wherein wherein the ischemic heart disease is myocardial infarction. The present invention relates to new compound 3-carboxy-N-ethyl-N,N-dimethylpropan-1-aminium salts, and to a method of preparation thereof (compound of formula 4)The present invention relates also to use of 3-carboxy-N-ethyl-N,N-dimethylpropan-1-aminium salts in the treatment of cardiovascular disease.Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels.An estimated 16.7 million—or 29.2% of total global deaths—result from the various forms of cardiovascular disease (CVD).Myocardial infarction (heart attack) is a serious result of coronary artery disease.Myocardial infarction (MI) is the irreversible necrosis of heart muscle secondary to ...

Cyclopentyl nucleoside analogs as anti-virals

Described herein are cyclopentyl nucleoside analogs of Formula (I), pharmaceutical compositions that include one or more cyclopentyl nucleoside analogs and methods of using the same to treat HBV, HDV and/or HIV. (I)

META-AZACYCLIC AMINO BENZOIC ACID DERIVATIVES AS PAN INTEGRIN ANTAGONISTS

The present disclosure provides pharmaceutical agents of the formula: 2. The pharmaceutical composition of claim 1 ,wherein:A is C—OH or N;{'sub': '(C≤8)', 'R′ is hydrogen, or alkyl; and'}{'sub': (C1-2)', '(C1-2)', '(C1-2), 'X and Y are each independently halo, fluoroalkoxy, alkyl, or fluoroalkyl.'}3. The pharmaceutical composition of claim 1 , wherein A is C—OH or N.4. The pharmaceutical composition of claim 1 , wherein A is N.5. The pharmaceutical composition of claim 1 , wherein A is C—OH.6. The pharmaceutical composition of claim 1 , wherein R′ is hydrogen.7. The pharmaceutical composition of claim 1 , wherein X is halo.8. The pharmaceutical composition of claim 7 , wherein X is —F claim 7 , —Cl claim 7 , or —Br.9. The pharmaceutical composition of claim 8 , wherein X is —Br or —Cl.10. The pharmaceutical composition claim 1 , wherein Y is fluoroalkoxy.11. The pharmaceutical composition of claim 10 , wherein Y is —OCF.12. The pharmaceutical composition of claim 1 , wherein Y is fluoroalkyl.13. The pharmaceutical composition of claim 9 , wherein Y is —CHFor —CF.14. The pharmaceutical composition of claim 9 , wherein Y is fluoroalkoxy.15. The pharmaceutical composition of claim 14 , wherein Y is —OCF.16. The pharmaceutical composition of claim 1 , wherein Y is alkyl.17. The pharmaceutical composition of claim 16 , wherein Y is —CH.20. A method of treating and/or preventing a disease or a disorder in a patient in need thereof claim 1 , comprising administering to the patient a composition of in an amount sufficient to treat and/or prevent the disease or disorder claim 1 , wherein the disease or disorder is associated with angiogenesis or fibrosis. Any and all priority claims identified in the Application Data Sheet, or any correction thereto, are hereby incorporated by reference under 37 CFR 1.57.The present disclosure relates to the fields of pharmaceuticals, medicine and cell biology. More specifically, it relates to pharmaceutical agents (compounds) which are ...

ANTIMICROBIAL COMPOUNDS AND METHODS OF MAKING AND USING THE SAME

The present invention relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, and reducing the risk of microbial infections in humans and animals. 3. The compound according to claim 2 , wherein Z is —NRCONR—; or a pharmaceutically acceptable salt claim 2 , ester claim 2 , tautomer claim 2 , or prodrug thereof.5. The compound according claim 4 , wherein (a) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,', '(b) a 3-14 member saturated, unsaturated, or aromatic carbocycle, and', '(c) a single bond,, 'A is selected from'}{'sup': '5', 'wherein (a) or (b) is optionally substituted with one or more Rgroups;'}{'sub': 1-8', '2-8', '2-8, 'claim-text': [{'sub': p', 'p', 'p, 'sup': 6', '6', '6', '6', '6, 'i) 0-4 carbon atoms in any of (a)-(c) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O)—, —NR—, —(C═O)—, —C(═NR)—, —S(O)NR—, and —NRS(O)NR—,'}, {'sup': '5', 'ii) any of (a)-(c) immediately above optionally is substituted with one or more Rgroups, and'}, {'sub': 1', '8, 'sup': '5', 'iii) any of (a)-(c) immediately above optionally is substituted with —(C-Calkyl)-Rgroups, and'}], 'B is selected from (a) —(Calkyl)-, (b) —(Calkenyl)-, (c) —(Calkynyl)-, (d) a single bond, wherein'}{'sub': 2', '2, 'C is selected from (a) NH, (b) —NHC(═NH)NHand (c) hydrogen;'}or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.6. The compound according to claim 5 , whereinA is selected from azepanyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, pyridinyl, cyclohexenyl, cyclohexadienyl, dihydropyridyl, furanyl, tetrahydrofuranyl, tetrahydropyridyl, azetidinyl, pyrrolidinyl, piperidinyl, and piperidenyl;{'sup': '5', 'wherein any of A immediately above optionally is substituted with one or more Rgroups;'} ...

Integrin antagonist conjugates for targeted delivery to cells expressing alpha-v-beta-3

The invention relates to compounds of formula (I): wherein R 1 , R 2 , and n are defined in the detailed description and claims. In particular, the present invention relates to the compounds of formula (I) for use in the manufacture and delivery of conjugated moieties such as small molecules, peptides, nucleic acids, fluorescent moieties, and polymers which are linked to alpha-V-beta-integrin antagonists to target cells expressing alpha-V-beta-3.

4-(4-cyano-2-thioaryl)dihydropyrimidinones and use thereof

The present invention relates to novel 4-(4-cyano-2-thioaryl)dihydropyrimidin-2-one derivatives, to processes for their preparation, to their use alone or in combination for the treatment and/or prevention of diseases and also to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of disorders of the lung and the cardiovascular system.

SYNTHESIS OF CYCLOCREATINE AND ANALOGS THEREOF

Provided herein is a process an intermediates for the preparation of a compound of formula (I): 2. The process according to claim 1 , wherein a carbon within the parentheses in the compound of formula (I) is optionally substituted with Rand R claim 1 , each of which independently of each other is hydrogen claim 1 , lower alkyl or cycloalkyl.3. The process according to claim 1 , wherein n is 1.4. The process according to claim 1 , wherein the compound of formula (I) is cyclocreatine or a pharmaceutically acceptable salt thereof.6. The process according to claim 1 , further comprising a precursor step of reacting ethylenediamine with chloroacetic acid to produce said compound of formula (II).7. The process according to claim 6 , wherein the concentration of cyanamide is 1-20 molar equivalents relative to a molar charge of said chloroacetic acid. The invention relates to a chemical process and intermediates for the preparation of cyclocreatine and related cyclic creatine analogs with application in the treatment of creatine transporter deficiency.All documents cited or relied upon below are expressly incorporated herein by reference.Cyclocreatine ((2-iminoimidazolidin-1-yl)acetic acid) is used in the treatment of creatine transporter defect. In this genetic disease, a mutation affects the creatine transporter thereby preventing creatine from crossing the blood-brain barrier (BBB), leading to a deficiency of this important amino acid in the brain. Creatine is a polar small molecule and requires active transport to cross the BBB. By contrast, cyclocreatine is more lipophilic owing to its two additional methylene groups and is able to cross the BBB by passive diffusion, thereby functioning as a creatine surrogate.The synthesis of cyclocreatine was first reported in Rowley, G. L.; Greenleaf, A. L.; Kenyon, G. L. 1971, 93, 5542-5551. The synthesis and characterization of cyclocreatine salts with pharmaceutically acceptable acids was later described in WO 2006/073923. The ...

INHIBITORS OF CREATINE TRANSPORT AND USES THEREOF

This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer. 2. The compound of claim 1 , wherein Ris hydrogen.4. The compound of any one of to claim 1 , wherein Rcombines with Rwith the atoms to which they are attached to form an optionally substituted C-Ccycloalkyl ring.7. The compound of any one of to claim 1 , wherein Ris hydrogen claim 1 , hydroxyl claim 1 , or NH.8. The compound of any one of to claim 1 , wherein Ris hydrogen.9. The compound of any one of to claim 1 , wherein m is 1 and Ris deuterium claim 1 , optionally substituted C-Calkyl claim 1 , optionally substituted C-Calkenyl claim 1 , optionally substituted C-Calkynyl claim 1 , or Rand Rcombine with the atoms to which they are attached to form an optionally substituted C-Ccycloalkyl ring.10. The compound of claim 9 , wherein Ris deuterium.11. The compound of claim 10 , wherein Ris deuterium.12. The compound of or claim 10 , wherein Rand Rare both deuterium.13. The compound of claim 9 , wherein Ris optionally substituted C-Calkyl claim 9 , optionally substituted C-Calkenyl claim 9 , optionally substituted C-Calkynyl.14. The compound of claim 13 , wherein Ris methyl claim 13 , ethyl claim 13 , n-propyl claim 13 , iso-propyl claim 13 , —CD claim 13 , —CF claim 13 , —CHF claim 13 , —CHF claim 13 , —CH═CH claim 13 , or —C≡CH.15. The compound of or claim 13 , wherein Ris hydrogen or methyl.16. The compound of any one of to claim 13 , wherein Ris hydrogen.17. The compound of any one of to claim 13 , wherein Ris hydrogen claim 13 , NH claim 13 , or methyl.18. The compound of claim 9 , wherein Rand Rcombine with the atoms to which they are attached to form an optionally substituted C-Ccycloalkyl ring.19. The compound of claim 18 , wherein said optionally substituted C-Ccycloalkyl ring is an optionally substituted C-Ccycloalkyl ring.20. The ...

NOVEL HETEROCYCLIC COMPOUNDS AND USE THEREOF IN MEDICINE AND IN COSMETICS

The invention relates to novel heterocyclic compounds of general formula (I), as well as their pharmaceutically acceptable salts, and their enantiomers. The invention also relates to the use thereof as a medicinal product, preferably in the prevention and/or treatment of inflammatory diseases with a neurogenic component or use thereof as a cosmetic. The compounds of the present invention act as antagonists of the CGRP-R receptor. 113-. (canceled)19. A pharmaceutical composition comprising the compound of formula (I) according to claim 14 , or an enantiomer thereof claim 14 , or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable vehicle.20. A cosmetic composition comprising the compound of formula (I) according to claim 14 , or an enantiomer thereof claim 14 , or a pharmaceutically acceptable salt thereof.21. A method of preventing and treating an inflammatory skin disease with a neurogenic component claim 19 , the method comprising administering the pharmaceutical composition according to claim 19 , to a patient claim 19 , wherein the inflammatory skin disease is rosacea claim 19 , atopic dermatitis claim 19 , chronic eczema of the hands claim 19 , psoriasis claim 19 , erythema claim 19 , or acne.22. The method according to claim 21 , wherein the rosacea is type I (erythematous) rosacea and type II (papulopustular) rosacea.23. The method according to claim 21 , wherein the psoriasis is psoriasis vulgaris claim 21 , psoriasis of the scalp claim 21 , arthritic psoriasis claim 21 , pustular psoriasis claim 21 , or guttate psoriasis.24. The method of claim 21 , wherein the erythema is facial erythema or erythema pudicitiae.25. The method of claim 21 , wherein the uticaria is acute uticaria claim 21 , senile uticaria claim 21 , puruitus uticaria claim 21 , or prurigo nodularis uticaria.26. The method according to claim 21 , wherein the inflammatory skin disease is type I (erythematous) rosacea claim 21 , atopic dermatitis claim 21 , psoriasis ...

META-AZACYCLIC AMINO BENZOIC ACID DERIVATIVES AS PAN INTEGRIN ANTAGONISTS

The present disclosure provides pharmaceutical agents of the formula: 2. The compound of claim 1 , wherein the carbon atom labeled β is in the S configuration.4. The compound of claim 2 , wherein A is N.5. The compound of claim 2 , wherein A is C—OH.6. The compound of claim 2 , wherein R′ is hydrogen.7. The compound of claim 2 , wherein X is halo.8. The compound of claim 7 , wherein X is —F claim 7 , —Cl claim 7 , or —Br.9. The compound of claim 8 , wherein X is —Br or —Cl.10. The compound claim 2 , wherein Y is fluoroalkoxy.11. The compound of claim 10 , wherein Y is —OCF.12. The compound of claim 2 , wherein Y is fluoroalkyl.13. The compound of claim 9 , wherein Y is —CHFor —CF.14. The compound of claim 9 , wherein Y is is fluoroalkoxy.15. The compound of claim 14 , wherein Y is —OCF.16. The compound of claim 2 , wherein Y is alkyl.17. The compound of claim 16 , wherein Y is —CH.19. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) the compound of ; and'}b) an excipient.20. A method of treating and/or preventing a disease or a disorder in a patient in need thereof claim 1 , comprising administering to the patient a compound of in an amount sufficient to treat and/or prevent the disease or disorder claim 1 , wherein the disease or disorder is associated with angiogenesis or fibrosis. Any and all priority claims identified in the Application Data Sheet, or any correction thereto, are hereby incorporated by reference under 37 CFR 1.57.The present disclosure relates to the fields of pharmaceuticals, medicine and cell biology. More specifically, it relates to pharmaceutical agents (compounds) which are useful as integrin receptor antagonists, with biological activity as antagonists of one or more integrins that mediate the pathologic processes of angiogenesis and fibrosis. As such, these compounds may be used are useful in pharmaceutical compositions and in methods for treating diseases and disorders, including conditions ...

ALPHA,BETA-UNSATURATED MONOMERS CAPABLE OF MULTIMERIZATION IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME

Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins. 1. A first monomer capable of forming a biologically useful multimer when in contact with one , two or more second monomers in an aqueous media , wherein the first monomer is represented by the formula:{'br': None, 'sup': 1', '1', '1, 'X—Y—Z\u2003\u2003(Formula I)'} [{'sup': '1', 'Xis a first ligand moiety capable of binding to and modulating a first target biomolecule;'}, {'sup': 1', '1', '1, 'Yis absent or is a connector moiety covalently bound to Xand Z;'}, {'sup': '1', 'Zis an activated π-moiety; and'}], 'and pharmaceutically acceptable salts, stereoisomers, metabolites and hydrates thereof, wherein'}{'sup': '1', 'the second monomer has a nucleophile moiety capable of binding with the Zmoiety of Formula I to form the multimer.'}3. The first monomer of claim 1 , wherein Ris independently selected claim 1 , for each occurrence claim 1 , from the group consisting of —C(O)— and —SO—.4. The first monomer of claim 1 , wherein Ais N.5. The first monomer of claim 1 , wherein Rand Rare hydrogen.1216.-. (canceled)17. The first monomer of claim 1 , wherein the second monomer may be represented by:{'br': None, 'sup': 2', '2', '2, 'X—Y—Z\u2003\u2003(Formula II),'} [{'sup': '2', 'Xis a second ligand moiety capable of binding to and modulating a second target biomolecule ...

Sulfonamide derivative or pharmaceutically acceptable acid-addition salt

The present invention aims to provide a novel low-molecular-weight compound showing an orexin receptor agonist activity and expected to be useful as a prophylactic or therapeutic agent for narcolepsy and the like. The present invention provides a compound represented by the formula (I): wherein each symbol is as described in the description, or a pharmaceutically acceptable acid addition salt thereof, which has an orexin receptor agonist activity, and an orexin receptor agonist containing the compound or a pharmaceutically acceptable acid addition salt thereof.

Use of 3-carboxy-n-ethyl-n,n-dimethylpropan-1-aminium salts in the treatment of cardiovascular disease

Salts of 3-carboxy-N-ethyl-N,N-dimethylpropan-1-aminium, method of preparation thereof and use in the treatment of cardiovascular disease.

Process for the Synthesis of Cyclic Alkylene Ureas

The invention relates to a process for the synthesis of cyclic alkylene ureas comprising reacting in the presence of a basic catalyst, a difunctional amine A having two primary amino groups, and an aliphatic organic carbonate component C selected from the group consisting of dialkyl carbonates CD and of alkylene carbonates CA, wherein the ratio of the amount of substance Ji(—NH2) of primary amino groups —NH2 in the difunctional amine A to the sum M(C) of the amount of substance n(CD) of carbonate groups of a dialkyl carbonate CD and the amount of substance n(CA) of carbonate groups in an alkylene carbonate CA, is at least more than 2, and to the product obtained by this process. 122-. (canceled)23. A process for the synthesis of a cyclic alkylene urea comprisingreacting a difunctional aliphatic amine A having two primary amino groups and an aliphatic organic carbonate component C selected from the group consisting of dialkyl carbonates CD and of alkylene carbonates CA, in the presence of a basic catalyst,{'sub': 2', '2, 'wherein the ratio of the amount of substance n(—NH) of primary amino groups —NHof the difunctional aliphatic amine A to the sum n(C) of the amount of substance n(CD) of carbonate groups of a dialkyl carbonate CD and the amount of substance n(CA) of carbonate groups in an alkylene carbonate CA, is at least more than 2.'}24. The process of claim 23 , wherein the process is conducted in the presence of a basic catalyst selected from the group consisting of alkoxides of alkali metals of group 1 of the Periodic Table of Elements claim 23 , and of alkoxides of alkaline earth metals of group 2 of the Periodic Table of Elements.25. The process of wherein the alkoxides are generated in situ.26. The process of wherein the alkoxides are generated by reacting an alkanol with a compound selected from the group consisting of an alkali hydroxide claim 25 , an alkali hydride claim 25 , an alkali amide claim 25 , an alkaline earth hydroxide claim 25 , an alkaline ...

Carboxamide compounds and their use as calpain inhibitors

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula I in which R 1 , R 2 , R 3a , R 3b , R 4 , Q, Y, A and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula Ia and Ib in which R 1 , r, R 2b , R 3a , R 3b , R 4 , Y and X have the meanings mentioned in the claims, including the tautomers thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Y is a moiety CH 2 —CH 2 , CH 2 —CH 2 —CH 2 , N(R y# )—CH 2 , N(R y# )—CH 2 —CH 2 or CH═CH—CH═, each optionally having 1 or 2 H-atoms replaced with identical or different radicals R y , wherein R y and R y# have the meanings mentioned in the claims.

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF

The application discloses pharmaceutical compounds of formula I useful for treating CNS diseases wherein m, s, RR, Rand Rare as defined herein. 2. The method of wherein m is 0 claim 1 , s is 1 claim 1 , Ris 3-fluoro claim 1 , Ris hydrogen and Ris acetyl claim 1 , aminocarbonyl or methylsulfonyl or a pharmaceutically acceptable salt.3. The method of wherein the compound is (R)-[6-(3-fluoro-benzenesulfonyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-naphthalen-1-ylmethyl]-urea or a pharmaceutically acceptable salt.4. The method of claim 3 , wherein the central nervous system disease state is depression.5. The method of claim 3 , wherein the central nervous system disease state is a memory disorder.6. The method of claim 3 , wherein the central nervous system disease state is Parkinson's disease. This Application is a Continuation of U.S. application Ser. No. 15/597,478, filed May 17, 2017, which is a Continuation of U.S. application Ser. No. 14/531,465, filed Nov. 3, 2014, which is a Continuation U.S. application Ser. No. 13/314,525, filed on Dec. 8, 2011, which is a Continuation of U.S. application Ser. No. 11/985,459, filed on Nov. 15, 2007, which is a continuation of U.S. patent application Ser. No. 11/315,706, filed Dec. 21, 2005, which claims the benefit under Title 35 U.S.C. 119(e) of U.S. Provisional Patent Application Ser. No. 60/638,030, filed Dec. 21, 2004, the disclosure of which is incorporated herein by reference in its entirety.This invention relates to substituted indane and tetralin compounds, and associated compositions, methods for use as therapeutic agents, and methods of preparation thereof.The actions of 5-hydroxytryptamine (5-HT) as a major modulatory neurotransmitter in the brain are mediated through a number of receptor families termed 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HTS, 5-HT6, and 5-HT7. Based on a high level of 5-HT6 receptor mRNA in the brain, it has been stated that the 5-HT6 receptor may play a role in the pathology and treatment of ...

PREPARATION AND USE OF SILVER SULFADIAZINE-IMMOBILIZED FILLERS

Silver sulfadiazine-immobilized inorganic fillers are described, and their synthesis is presented. The fillers are believed to have utility in dental composites and dental adhesives to achieve potent, long-term, and none-leaching antimicrobial effects. 1. A composition of matter , comprising:a particulate substrate comprising an inorganic filler;an amine-terminated hydrocarbon molecule moiety covalently bonded by way of a carbon atom of said hydrocarbon molecule moiety to said inorganic filler;a cyanuric chloride molecule moiety bonded to an amine group of said amine-terminated hydrocarbon molecule moiety;a sulfadiazine molecule moiety bonded to said cyanuric chloride molecule moiety; anda silver metal ion incorporated in said sulfadiazine moiety.2. The composition of matter of claim 1 , wherein a second sulfadiazine molecule moiety is bonded to said cyanuric chloride molecule moiety.3. The composition of matter of claim 2 , wherein said second sulfadiazine molecule moiety has a second silver metal ion incorporated therein.4. The composition of matter of claim 1 , wherein said particulate substrate comprising an inorganic filler is a particulate glass substrate.5. The composition of matter of claim 4 , wherein said particulate glass substrate comprises a glass containing BaO.6. The composition of matter of claim 1 , wherein said amine-terminated hydrocarbon molecule moiety is (3-aminopropyl)trimethoxysilane.7. A method of producing a composition of matter claim 1 , comprising the steps of:providing a particulate substrate comprising an inorganic filler;reacting said inorganic filler with an amine-terminated hydrocarbon molecule moiety to covalently bond said hydrocarbon molecule moiety by way of a carbon atom thereof to said inorganic filler to produce an amine modified substrate;reacting said amine modified substrate with a cyanuric chloride molecule moiety to bond said cyanuric chloride molecule moiety to an amine group of said amine-terminated hydrocarbon ...

ALPHA-5 BETA-1 INHIBITORS

The disclosure provides, inter alia, alpha-5 beta-1 inhibitors, pharmaceutical compositions comprising alpha-5 beta-1 inhibitors, methods for treating diseases using alpha-5 beta-1 inhibitors, and processes for making alpha-5 beta-1 inhibitors. 2. The compound of claim 1 , wherein Ais C(R) claim 1 , and Ais C(R).3. The compound of claim 1 , wherein Ais N claim 1 , and Ais C(R) or N.4. The compound of claim 1 , wherein m is 1 or 2.5. The compound of claim 1 , wherein X is a bond claim 1 , —C(R)(R)— claim 1 , or —N(R).6. The compound of claim 1 , wherein Lis a bond claim 1 , —NH— claim 1 , —(CH)—NH— claim 1 , —(CH)— claim 1 , or —(CH)—N((CH)CH)—C(═O)— claim 1 , wherein z1 claim 1 , z2 claim 1 , and z3 are each independently an integer from 1 to 10; and z4 is an integer from 0 to 9.7. The compound of claim 1 , wherein Ris hydrogen claim 1 , halogen claim 1 , —CX claim 1 , —CHX claim 1 , —CHX claim 1 , —OCX claim 1 , —OCHX claim 1 , —OCHX claim 1 , —SOR claim 1 , —SONRR claim 1 , —CN claim 1 , —C(O)R claim 1 , —C(O)OR claim 1 , —C(O)NRR claim 1 , —OR claim 1 , —ONRR claim 1 , —NHC(O)NRR claim 1 , —N(O) claim 1 , —NRR claim 1 , —NHNRR claim 1 , —NRSOR claim 1 , —NRC(O)R claim 1 , —NRC(O)OR claim 1 , —NROR claim 1 , —N claim 1 , substituted alkyl claim 1 , substituted or unsubstituted heteroalkyl claim 1 , substituted or unsubstituted cycloalkyl claim 1 , substituted or unsubstituted heterocycloalkyl claim 1 , substituted or unsubstituted aryl claim 1 , or substituted or unsubstituted heteroaryl.8. The compound of claim 1 , wherein Ris halogen claim 1 , —CX claim 1 , —CHX claim 1 , —CHX claim 1 , —OCX claim 1 , —OCHX claim 1 , or —OCHX; Ris halogen claim 1 , —CX claim 1 , —CHX claim 1 , —CHX claim 1 , —OCX claim 1 , —OCHX claim 1 , or —OCHX; and Xand Xare each independently chlorine or fluorine.9. The compound of claim 1 , wherein Ris halogen and Ris halogen or unsubstituted Calkyl.10. The compound of claim 1 , wherein Ris hydrogen claim 1 , halogen claim 1 , substituted ...

Sulfonamide derivative and pharmaceutically acceptable acid addition salt thereof

The present invention aims to provide a novel low-molecular-weight compound exhibiting an orexin receptor agonist activity and expected to be useful as a prophylactic or therapeutic agent for narcolepsy and the like. The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a pharmaceutically acceptable acid addition salt thereof, which has an orexin receptor agonist activity, and an orexin receptor agonist containing the compound or a pharmaceutically acceptable acid addition salt thereof.

A Manufacturing Process for 2-Nitroimino Heterocyclic Compounds

The present invention relates to a process for manufacture of 2-nitroimino heterocyclic compounds and intermediates thereof. More particularly, the present invention relates to a convenient manufacturing process for preparation of 2-nitroimino imidazolidine compounds. 2. The process as claimed in claim 1 , wherein said nitroimino heterocyclic compound of Formula B is prepared using a diamine of Formula III wherein n is 2.3. The process as claimed in claim 1 , wherein said nitroimino heterocyclic compound of Formula B is prepared using a diamine of Formula III wherein n is 3.5. The process as claimed in claim 1 , wherein said acid is sulfuric acid.6. The process as claimed in claim 1 , wherein the reaction proceeds without isolation of compound of Formula II.7. The process as claimed in claim 1 , wherein the reaction is carried out at a temperature in the range of about of 5° C. to about 50° C. The present invention relates to a process for manufacture of 2-nitroimino heterocyclic compounds and intermediates thereof. More particularly, the present invention relates to a convenient manufacturing process for preparation of 2-nitroimino imidazolidine compounds.Nitroimino heterocyclic compounds of general Formula A are useful intermediates for certain insecticides and for products with certain medicinal applications. Imidacloprid is one such widely used insecticide.wherein R, Rand Rare the same or different and represent hydrogen or a lower alkyl of 1 to 4 carbon atoms, optionally substituted with a heterocyclic ring wherein one of the ring atoms comprises nitrogen, and wherein said ring is being optionally substituted with halogen or lower alkyl of 1 to 4 carbon atoms, and n is 2, 3 or 4.Imidacloprid is a systemic insecticide with translaminar activity and with contact and stomach action. It is widely used for controlling of sucking insects, including rice-, leaf- and plant hoppers, aphids, thrips and whitefly. It is also found to be effective against soil insects, ...

Reduction of Aldehydes in Amine Catalysts

The present disclosure provides a method for reducing the aldehyde content in an amine catalyst by treating the amine catalyst with a treating agent selected from a cyclic urea substituted with at least one isocyanate reactive group, a free radical scavenger and a mixture thereof. The treated amine catalyst may then be used in the production of polyurethane materials which exhibit reduced aldehyde emissions.

AMINODIHYDROTHIAZINE DERIVATIVES

A composition having BACE 1 inhibitory activity containing a compound represented by the general formula (I): 2. (canceled)3. (canceled)4. The compound according to claim 1 , wherein E is a bond claim 1 , its pharmaceutically acceptable salt claim 1 , or a solvate thereof.5. (canceled)6. (canceled)7. (canceled)8. The compound according to claim 1 , wherein Ris optionally substituted lower alkyl claim 1 , optionally substituted lower alkenyl claim 1 , optionally substituted lower alkynyl claim 1 , an optionally substituted carbocyclic group claim 1 , or an optionally substituted heterocyclic group claim 1 ,lower alkyl being substituted optionally with at least one selected from the group consisting of the substituent α, the substituent α being at least one selected from the group consisting of halogen, hydroxy, lower alkoxy, hydroxy lower alkoxy, lower alkoxy lower alkoxy, acyl, acyloxy, carboxy, lower alkoxycarbonyl, amino, acylamino, lower alkylamino, lower alkylthio, carbamoyl, lower alkylcarbamoyl, hydroxy lower alkylcarbamoyl, sulfamoyl, lower alkylsulfamoyl, lower alkylsulfinyl, cyano, nitro, aryl, and heterocyclic group,lower alkenyl being substituted optionally with the substituent α,lower alkynyl being substituted optionally with the substituent α, andthe carbocyclic group and the heterocyclic group being substituted optionally with at least one selected from the group consisting of the substituent α and lower alkyl,its pharmaceutically acceptable salt, or a solvate thereof.9. The compound according to claim 1 , wherein Ris a hydrogen atom; Ris a hydrogen atom claim 1 , optionally substituted lower alkyl claim 1 , optionally substituted acyl claim 1 , optionally substituted lower alkylsulfonyl claim 1 , or optionally substituted amidino claim 1 ,lower alkyl being substituted optionally with at least one selected from the group consisting of the substituent α, the substituent α being at least one selected from the group consisting of halogen, hydroxy, lower ...

ACTIVE LIGHT SENSITIVE OR RADIATION SENSITIVE RESIN COMPOSITION, ACTIVE LIGHT SENSITIVE OR RADIATION SENSITIVE FILM, MASK BLANK PROVIDED WITH ACTIVE LIGHT SENSITIVE OR RADIATION SENSITIVE FILM, PATTERN FORMING METHOD, METHOD FOR MANUFACTURING ELECTRONIC DEVICE, ELECTRONIC DEVICE AND NOVEL COMPOUND

There is provided an active light sensitive or radiation sensitive resin composition which contains (A) an alkali soluble resin and (C) a cross-linking agent represented by the following General Formula (1-0). 3. The active light sensitive or radiation sensitive resin composition according to claim 1 , further comprising:a compound (B) that generates an acid by irradiation with active light or radiation.4. The active light sensitive or radiation sensitive resin composition according to claim 3 ,wherein the compound (B) that generates an acid by irradiation with active light or radiation is a sulfonium salt.5. The active light sensitive or radiation sensitive resin composition according to claim 1 ,wherein the molecular weight of the cross-linking agent (C) is 450 or greater.6. The active light sensitive or radiation sensitive resin composition according to claim 5 ,wherein the molecular weight of the cross-linking agent (C) is 450 to 1500.8. An active light sensitive or radiation sensitive film which is formed of the active light sensitive or radiation sensitive resin composition according to .9. A mask blank provided with the active light sensitive or radiation sensitive film according to .10. A pattern forming method claim 8 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a step of forming a film by applying the active light sensitive or radiation sensitive resin composition to a substrate;'}a step of exposing the film; anda step of forming a negative-type pattern by developing the exposed film.11. A method for manufacturing an electronic device claim 8 , comprising:{'claim-ref': {'@idref': 'CLM-00010', 'claim 10'}, 'the pattern forming method according to .'}13. The compound according to claim 12 ,{'sub': '1', 'wherein at least one Yin General Formula (1) is a nitrogen atom.'} This application is a Continuation application of PCT Application No. PCT/JP2014/075682, filed Sep. 26, 2014, and based upon and claiming the benefit of priority from ...

META-AZACYCLIC AMINO BENZOIC ACID DERIVATIVES AS PAN INTEGRIN ANTAGONISTS

The present disclosure provides pharmaceutical agents of the formula: 2. The method of claim 1 , wherein X is —F claim 1 , —Cl claim 1 , or —Br.3. The method of claim 2 , wherein X is —Cl or —Br.4. The method of claim 1 , wherein Y is —OCF claim 1 , —CHF claim 1 , —CF claim 1 , or —CH.5. The method of claim 3 , wherein Y is —OCF claim 3 , —CHFor —CF.7. The method of claim 6 , wherein the inorganic base is a metal hydroxide selected from the group consisting of hydroxides of sodium claim 6 , potassium claim 6 , lithium claim 6 , calcium claim 6 , magnesium claim 6 , iron claim 6 , zinc claim 6 , copper claim 6 , manganese claim 6 , and aluminum.8. The method of claim 7 , wherein the inorganic base is lithium hydroxide.10. The method of claim 9 , wherein the mineral acid is selected from the group consisting of HCl claim 9 , HNO claim 9 , HPO claim 9 , HSO claim 9 , HBr claim 9 , and HClO.12. The method of claim 11 , wherein X is —F claim 11 , —Cl claim 11 , or —Br.13. The method of claim 12 , wherein X is —Cl or —Br.14. The method of claim 11 , wherein Y is —OCF claim 11 , —CHF claim 11 , —CF claim 11 , or —CH.15. The method of claim 13 , wherein Y is —OCF claim 13 , —CHFor —CF.17. The method of claim 16 , wherein the inorganic base is a metal hydroxide selected from the group consisting of hydroxides of sodium claim 16 , potassium claim 16 , lithium claim 16 , calcium claim 16 , magnesium claim 16 , iron claim 16 , zinc claim 16 , copper claim 16 , manganese claim 16 , and aluminum.18. The method of claim 17 , wherein the inorganic base is lithium hydroxide.22. The compound of claim 21 , wherein X is —F claim 21 , —Cl claim 21 , or —Br.23. The compound of claim 22 , wherein X is —Cl or —Br.24. The compound of claim 21 , wherein Y is —OCF claim 21 , —CHF claim 21 , —CF claim 21 , or —CH.25. The compound of claim 23 , wherein Y is —OCF claim 23 , —CHFor —CF.27. The method of claim 26 , wherein X is —F claim 26 , —Cl claim 26 , or —Br.28. The method of claim 27 , ...

Crystalline Pharmaceutical

New crystalline forms of lopinavir are disclosed. 1. A hydrated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 7.25°±0.1° , 8.53°±0.1° , 10.46°±0.1° , 11.05°±0.1° , 11.71°±0.1° , 14.76°±0.1° , 15.30°±0.1° , 16.67°±0.1° , 17.32°±0.1° , 19.10°±0.1° , 19.57°±0.1° , 21.24°±0.1° , 21.84°±0.1° and 22.46°±0.1°.2. A higher hydrated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 3.89°±0.1° , 6.55°±0.1° , 7.76°±0.1° , 8.55°±0.1° , 9.70°±0.1° , 10.56°±0.1° , 14.76°±0.1° , 15.57°±0.1° , 18.30°±0.1° , 18.95°±0.1° and 22.74°±0.1°.3. A higher hydrated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 3.89°±0.1° , 6.55°±0.1° , 7.76°±0.1° , 8.55°±0.1° , 9.70°±0.1° , 10.56°±0.1° , 14.76°±0.1° , 15.06°±0.1° , 15.57°±0.1° , 16.49°±0.1° , 17.51°±0.1° , 18.30°±0.1° , 18.95°±0.1° , 21.73°±0.1° and 22.74°±0.1°.4. A solvated crystalline form of lopinavir with characteristic peaks in the solid state infrared spectrum at a position within the ranges of 1661-1673 cm , 1645-1653 cmand 1619-1629 cm.5. A desolvated crystalline form of lopinavir with at least one characteristic peak in the solid state infrared spectrum at a position within the range 1655-1662 cm.6. A desolvated crystalline form of lopinavir with characteristic peaks in the solid state infrared spectrum at a position within the ranges of 1655-1662 cmand 1636-1647 cm.7. A desolvated crystal form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 4.85°±0.1° , 6.39°±0.1° , 7.32°±0.1° , 8.81°±0.1° , 12.20°±0.1° , 12.81°±0.1° , 14.77°±0.1° , 16.45°±0.1° and 17.70°±0.1°.8. A desolvated crystal form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 4.85°±0.1° , 6.39°±0.1° , 7.32°±0.1° , 8.81°±0.1° , 12.20°±0.1° , ...

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF

The application discloses pharmaceutical compounds of formula I useful for treating CNS diseases wherein m, s, RR, Rand Rare as defined herein. 2. The method of wherein m is 0 claim 1 , s is 1 claim 1 , Ris 3-fluoro claim 1 , Ris hydrogen and Ris acetyl claim 1 , aminocarbonyl or methylsulfonyl or a pharmaceutically acceptable salt.3. The method of wherein the compound is (R)-[6-(3-fluoro-benzenesulfonyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-naphthalen-1-ylmethyl]-urea or a pharmaceutically acceptable salt.4. The method of claim 3 , wherein the central nervous system disease state is depression.5. The method of claim 3 , wherein the central nervous system disease state is a memory disorder.6. The method of claim 3 , wherein the central nervous system disease state is Parkinson's disease. This application is a Continuation of U.S. application Ser. No. 14/531,465 filed Nov. 3, 2014 which is a Continuation U.S. application Ser. No. 13/314,525 filed on Dec. 8, 2011, which is a Continuation of U.S. application Ser. No. 11/985,459 filed on Nov. 15, 2007, which is a continuation of U.S. patent application Ser. No. 11/315,706 filed Dec. 21, 2005, which claims the benefit under Title 35 U.S.C. 119(e) of U.S. Provisional Patent Application Ser. No. 60/638,030 filed Dec. 21, 2004, the disclosure of which is incorporated herein by reference in its entirety.This invention relates to substituted indane and tetralin compounds, and associated compositions, methods for use as therapeutic agents, and methods of preparation thereof.The actions of 5-hydroxytryptamine (5-HT) as a major modulatory neurotransmitter in the brain are mediated through a number of receptor families termed 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7. Based on a high level of 5-HT6 receptor mRNA in the brain, it has been stated that the 5-HT6 receptor may play a role in the pathology and treatment of central nerve system disorders. In particular, 5-HT2-selective and 5-HT6 selective ligands have ...

Tetralin and indane derivatives and uses thereof

Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, p, q, Ar, R 1 and R 2 are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formula I.

ANTI-ALPHAVBETA1 INTEGRIN INHIBITORS AND METHODS OF USE

Provided herein, inter alia, are methods and compositions for inhibiting αvβ1 integrin and for treating fibrosis. 2. The compound of claim 1 , wherein Ris a substituted or unsubstituted alkyl claim 1 , or substituted or unsubstituted heteroalkyl.3. The compound of claim 1 , wherein Ring C is phenyl or Ring C is 5 to 6 membered heteroaryl and z1 is an integer between 0 to 3.4. The compound of claim 1 , wherein Ring A is unsubstituted phenyl or unsubstituted 5 to 6 membered heteroaryl.5. The compound of claim 1 , wherein Ris —NRRor substituted or unsubstituted heteroaryl.6. The compound of claim 1 , wherein Ris a substituted pyridyl claim 1 , substituted imidazolyl claim 1 , substituted oxazolyl claim 1 , substituted thiazolyl claim 1 , substituted oxadiazolyl claim 1 , substituted triazolyl or substituted thiadiazolyl.7. The compound of claim 1 , wherein Ris a substituted heterocycloalkyl.8. The compound of claim 1 , wherein Ris —C(NH)NH claim 1 , —C(NH)R claim 1 , —C(NR)NH claim 1 , —C(NR)R claim 1 , —C(NCN)NH claim 1 , —NH claim 1 , —C(NH)NHR claim 1 , —C(NR)NHR claim 1 , or —C(NCN)NHR.9. The compound of claim 1 , wherein Lis unsubstituted C-Calkylene or unsubstituted 2 to 5 membered heteroalkylene.10. The compound of claim 1 , wherein Lis substituted or unsubstituted C-Calkylene claim 1 , substituted or unsubstituted 2 to 8 membered heteroalkylene claim 1 , unsubstituted phenylene claim 1 , unsubstituted 5 to 6 membered heteroarylene claim 1 , or unsubstituted alkylarylene.11. The compound of claim 1 , wherein{'sup': 3', '6, 'sub': 1', '3, 'Lis R-substituted C-Calkylene;'}{'sup': 6', '6A, 'Ris —NHC(O)R;'}{'sup': 6A', '6C', '6C', '6C', '6C, 'Ris —C(NCN)R, —C(NH)R, R-substituted or unsubstituted alkyl, or R-substituted or unsubstituted heteroalkyl;'}{'sup': 6C', '6D', '6D', '6D', '6E', '6E', '6D', '6E', '6D', '6D', '6D', '6D', '6E', '6D', '6E', '6D', '6E', '6D', '6D', '6F', '6F', '6F', '6F', '6F', '6F, 'sub': 3', '3', '3', '3', '3', '2', 'n6, 'Ris hydrogen, halogen, ...

6-MEMBERED URACIL ISOSTERES

Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions. 14. The compound of any one of - , wherein Lis —S(O)NR— wherein the sulfur is attached to L.19. The compound of claim 5 , wherein Ris H.20. The compound of claim 5 , wherein Ris H or —OR.21. The compound of claim 5 , wherein Ris F or H.27. A compound selected from Table 1 or Table 2.28. A composition comprising a compound of any one of to claim 5 , and at least one excipient or carrier claim 5 , optionally a pharmaceutically acceptable carrier.29. A method of one or more of inhibiting dUTPase or enhancing the efficacy of a dUTPase directed therapy comprising contacting the dUTPase with a therapeutically effective amount of the compound of any of to .30. A method of reversing resistance to a dUTPase-directed therapy comprising contacting the dUTPase with a therapeutically effective amount of the compound of any of to .31. A method of treating a disease whose treatment is impeded by the expression or over expression of dUTPase claim 5 , comprising administering to a patient in need of such treatment a therapeutically effective amount of the compound of any of to .32. A method of inhibiting the growth of a cancer cell comprising contacting the cell with a therapeutically effective amount of the compound of any of to and a therapeutically effective amount of a dUTPase directed therapeutic claim 5 , thereby inhibiting the growth of the cancer cell.33. The method of claim 32 , wherein the cancer cell is selected from a colon cancer cell claim 32 , a colorectal cancer cell claim 32 , a gastric cancer cell claim 32 , a head and neck cancer cell claim 32 , a breast cancer cell claim 32 , a lung cancer cell or a blood cell.34. A method of treating a disease in a patient whose treatment is impeded by the expression or overexpression of dUTPase claim 32 , comprising:a. screening a cell or tissue sample from the patient;b. determining the ...

Novel 2,3-Dihydro-1h-imidazo{1,2-a}pyrimidin-5-one and this 1,2,3,4-tetrahydropyrimido{1,2-a}pyrimidin-6-one Derivatives Comprising a Substituted Morpholine, Preparation Thereof and Pharmaceutical Use Thereof

The invention relates to the novel products of formula (I): 3. The compound of formula (I) as defined in claim , in which p is the integer 0 and q is the integer 2 or else p is the integer 2 and q is the integer 0;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the radicals R1, R2, R3 and R4 and the morpholine residue having the meanings indicated in ,'}said products of formula (I) being in any of the possible racemic, enantiomeric and diastereoisomeric isomer forms, and also the addition salts with inorganic and organic acids or with inorganic and organic bases of said products of formula (I).4. The compound of formula (I) as defined in claim 1 , in which p is the integer 0 and q is the integer 1 or else p is the integer 1 and q is the integer 0;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the radicals R1, R2, R3 and R4 and the morpholine residue having the meanings indicated in ,'}said products of formula (I) being in any of the possible racemic, enantiomeric and diastereoisomeric isomer forms, and also the addition salts with inorganic and organic acids or with inorganic and organic bases of said products of formula (I).5. The compound of formula (I) as defined in claim 1 , corresponding to the following formulae:(S)-2-((R)-3-Methylmorpholin-4-yl)-9-(5-methyl-[1,2,4]oxadiazol-3-ylmethyl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one(S)-3-Fluoro-9-(2-fluoropyridin-4-ylmethyl)-2-((R)-3-methylmorpholin-4-yl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one(S)-2-((3R,5R)-3,5-Dimethylmorpholin-4-yl)-9-isoxazol-5-ylmethyl-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one(S)-9-(3-Methylisoxazol-4-ylmethyl)-2-((R)-3-methylmorpholin-4-yl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one(R)-2-((R)-3-Methylmorpholin-4-yl)-9-oxazol-2-ylmethyl-6-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one(S)-3-Fluoro-2-((R)-3-methylmorpholin-4-yl)-9-(5-methyl-[1,2,4]oxadiazol-3-ylmethyl)-8- ...

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF

The applicaton discloses pharmaceutical compounds of formula I useful for treating CNS diseases wherein m, s, RR, Rand Rare as defined herein. 2. The method of wherein m is 0 claim 1 , s is 1 claim 1 , Ris 3-fluoro claim 1 , Ris hydrogen and Ris acetyl claim 1 , aminocarbonyl or methylsulfonyl or a pharmaceutically acceptable salt..3. The method of wherein the compound is (R)-[6-(3-fluoro-benzenesulfonyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-naphthalen-1-ylmethyl]-urea or a pharmaceutically acceptable salt.4. The method of claim 3 , wherein the central nervous system disease state is depression.5. The method of claim 3 , wherein the central nervous system disease state is a memory disorder.6. The method of claim 3 , wherein the central nervous system disease state is Parkinson's disease. This Application is a Continuation of U.S. application Ser. No. 15/597,478, filed May 17, 2017, which is a Continuation of U.S. application Ser. No. 14/531,465, filed Nov. 3, 2014, which is a Continuation U.S. application Ser. No. 13/314,525, filed on Dec. 8, 2011, which is a Continuation of U.S. application Ser. No. 11/985,459, filed on Nov. 15, 2007, which is a continuation of U.S. patent application Ser. No. 11/315,706, filed Dec. 21 2005, which claims the benefit under Title 35 U.S.C. 119(e) of U.S. Provisional Patent Application Ser. No. 60/638,030, filed Dec. 21, 2004, the disclosure of which is incorporated herein by reference in its entirety.This invention relates to substituted indane and tetralin compounds, and associated compositions, methods for use as therapeutic agents, and methods of preparation thereof.The actions of 5-hydroxytryptamine (5-HT) as a major modulatory neurotransmitter in the brain are mediated through a number of receptor families termed 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7. Based on a high level of 5-HT6 receptor mRNA in the brain, it has been stated that the 5-HT6 receptor may play a role in the pathology and treatment of ...

INHIBITORS OF CREATINE TRANSPORT AND USES THEREOF

This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer. 3. The method of claim 2 , wherein said method comprises the suppression of metastatic colonization of said migrating cancer in the liver.4. The method of claim 2 , wherein said migrating cancer is metastatic cancer.5. The method of claim 4 , wherein the metastatic cancer comprises cells exhibiting migration and/or invasion of migrating cells.6. The method of claim 4 , wherein said metastatic cancer comprises cells exhibiting endothelial recruitment and/or angiogenesis.7. The method of claim 2 , wherein said migrating cancer spreads via seeding the surface of the peritoneal claim 2 , pleural claim 2 , pericardial claim 2 , or subarachnoid spaces.8. The method of claim 2 , wherein said migrating cancer spreads via the lymphatic system.9. The method of claim 2 , wherein said migrating cancer spreads hematogenously.10. The method of claim 2 , wherein said migrating cancer is a cell migration cancer.11. The method of claim 10 , wherein said cell migration cancer is a non-metastatic cell migration cancer.12. The method of claim 11 , where said cell migration cancer is ovarian cancer claim 11 , mesothelioma claim 11 , or primary lung cancer.13. The method of claim 1 , wherein said cancer is breast cancer claim 1 , colon cancer claim 1 , renal cell cancer claim 1 , non-small cell lung cancer claim 1 , hepatocellular carcinoma claim 1 , gastric cancer claim 1 , ovarian cancer claim 1 , pancreatic cancer claim 1 , esophageal cancer claim 1 , prostate cancer claim 1 , sarcoma claim 1 , or melanoma.14. The method of claim 1 , wherein said cancer is gastrointestinal cancer.15. The method of claim 14 , wherein said gastrointestinal cancer is esophageal cancer claim 14 , stomach cancer claim 14 , pancreatic cancer claim 14 , liver cancer claim 14 , ...

AGRICULTURAL CHEMICALS

The present invention relates to compounds which are of use in the field of agriculture as herbicides. The invention also relates to methods of using said compounds and compositions comprising said compounds. 4. A compound of wherein Ris H.5. A compound of wherein Ris H.6. A compound of claim 1 , wherein Ris independently selected from fluoro claim 1 , C-C-haloalkyl and C-C-alkyl.7. A compound of claim 1 , wherein Rand Rtogether with the carbon atom to which they are attached form a C-C-cycloalkyl group; wherein the cycloalkyl group is optionally substituted with from 1 to 4 Rgroups.8. A compound of claim 7 , wherein Rand Rtogether with the carbon atom to which they are attached form a cyclopropyl group; wherein the cyclopropyl group is optionally substituted with from 1 to 4 Rgroups.9. A compound of claim 7 , wherein Rand Rtogether with the carbon atom to which they are attached form a cyclobutyl group; wherein the cyclobutyl group is optionally substituted with from 1 to 4 Rgroups.10. A compound of claim 7 , wherein Rand Rtogether with the carbon atom to which they are attached form a cyclopentyl group; wherein the cyclopentyl group is optionally substituted with from 1 to 4 Rgroups.11. A compound of claim 7 , wherein Rand Rmay together with the carbon atom to which they are attached form a cyclohexyl group; wherein the cyclohexyl group is optionally substituted with from 1 to 4 Rgroups.13. A compound of claim 12 , wherein r is 1 and s is 1.14. A compound of claim 12 , wherein r is 0 and s is 2.15. A compound of claim 12 , wherein r is 1 and s is 2.16. A compound of claim 12 , wherein r is 0 and s is 3.17. A compound of claim 12 , wherein r is 2 and s is 2.18. A compound of claim 12 , wherein r is 1 and s is 3.19. A compound of claim 12 , wherein r is 0 and s is 4.20. A compound of claim 12 , wherein X is NR.21. A compound of claim 12 , wherein X is O.22. A compound of claim 12 , wherein X is S.23. A compound of claim 12 , wherein X is SO.24. A compound of claim ...

Antimicrobial Compounds And Methods Of Making And Using The Same

The present invention relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, and reducing the risk of microbial infections in humans and animals. 2. The compound according to claim 1 , wherein Z is selected from the group —NR claim 1 , —NRCO— claim 1 , and —NRCONR—; or a pharmaceutically acceptable salt claim 1 , ester claim 1 , or tautomer thereof.3. The compound according to claim 2 , wherein Z is —NRCONR—; or a pharmaceutically acceptable salt claim 2 , ester claim 2 , or tautomer thereof.4. The compound according to claim 3 , wherein Z is —NHCONH—; or a pharmaceutically acceptable salt claim 3 , ester claim 3 , or tautomer thereof.5. The compound according claim 4 , wherein:A is (c) a single bond,{'sub': '1-8', 'claim-text': [{'sup': 6', '6, 'i) 0-4 carbon atoms in (a) immediately above optionally is replaced by a moiety selected from the group consisting of —NR—, —(C═O)—, and —C(═NR)—,'}, {'sup': '5', 'ii) (a) immediately above optionally is substituted with one or more Rgroups, and'}, {'sub': 1', '8, 'sup': '5', 'iii) (a) immediately above optionally is substituted with —(C-Calkyl)-Rgroups, and'}], 'B is selected from (a) —(Calkyl)- and (d) a single bond, wherein'}{'sub': 2', '2, 'C is selected from (a) NH, (b) —NHC(═NH)NHand (c) hydrogen;'}or a pharmaceutically acceptable salt, ester, or tautomer thereof.6. The compound according to claim 5 , wherein:A is a single bond;{'sub': '1-8', 'claim-text': [{'sup': '6', 'i) 0-4 carbon atoms in (a) immediately above optionally is replaced by a moiety selected from the group consisting of —NR— and —(C═O)—,'}, {'sup': '5', 'ii) (a) immediately above optionally is substituted with one or more Rgroups, and'}, {'sub': '1-8', 'sup': '5', 'iii) (a) immediately above optionally is substituted with —(Calkyl)-Rgroups; and'}], 'B is (a) —(Calkyl)-, wherein'}alternatively, B is a single bond;{'sub': 2', '2, 'C is selected from (a) NH, ...

THERAPEUTIC COMPOUNDS

The invention provides methods for producing analgesia in an animal comprising administering to the animal a compound of the formula Ia′, Ib′, Ic′, and Id′:

ANTIVIRAL COMPOUNDS AND USES THEREOF

This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions. 125-. (canceled)28. The compound or salt of claim 27 , wherein n is 1.29. The compound or salt of claim 27 , wherein n is 2.30. The compound or salt of claim 27 , wherein Ris amino.31. The compound or salt of claim 27 , wherein Ris tert-butoxycarbonylamino.33. The compound or salt of claim 32 , wherein m is 0.34. The compound or salt of claim 32 , wherein m is 2.35. The compound or salt of claim 32 , wherein Ris hydrogen.36. The compound or salt of claim 32 , wherein Ris phenyl.37. The compound or salt of claim 32 , wherein Ris C-C-alkyl.38. The compound or salt of claim 32 , wherein Ris C-C-alkyloxy-carbonyl.39. The compound or salt of claim 26 , wherein Ris benzoyl.40. The compound or salt of claim 26 , wherein Ris selected from the group consisting of tert-butyl claim 26 , perfluoroethyl claim 26 , and trifluoromethyl.41. The compound or salt of claim 26 , wherein Ris selected from the group consisting of furanyl claim 26 , pyrazolyl claim 26 , and thiophenyl claim 26 , wherein each such substituent optionally is substituted with methyl.42. The compound or salt of claim 26 , wherein Ris selected from the group consisting of C-C-alkenyl claim 26 , C-C-alkyl claim 26 , alkyloxy claim 26 , amino claim 26 , and halo.43. The compound or salt of claim 26 , wherein Ris methoxy.44. The compound or salt of claim 26 , wherein Ris selected from the group consisting of naphthalenyl claim 26 , dihydronaphthalenyl claim 26 , tetrahydronaphthalenyl claim 26 , hexahydronaphthalenyl claim 26 , octahydronaphthalenyl claim 26 , decahydronaphthalenyl claim 26 , ...

PROCESS TO PREPARE PROPYLENE AMINES AND PROPYLENE AMINE DERIVATIVES

A process is provided to prepare propylene amines of the formula NH—(A—NH—)R, wherein R is a hydrogen atom or an alkyl group, p is at least 1 when R is an alkyl group, and at least 2 when R is a hydrogen atom, or derivatives or precursors thereof wherein one or more units —NH—A—NH— may be present as a cyclic urea unit 2. The process of wherein the molar ratio of carbon oxide delivering agent to amine-functional compound is at least about 0.6:1.3. (canceled)4. The process of claim 1 , wherein the molar ratio of hydroxy-functional compound to amine-functional compound is at least about 0.7:1 and the molar ratio of carbon oxide delivering agent to amine-functional compound is at least about 0.05:1.5. (canceled)6. (canceled)7. The process of claim 1 , wherein the molar ratio of hydroxy-functional compound to amine-functional compound is from about 0.05:1 to about 0.7:1 and the molar ratio of carbon oxide delivering agent to amine-functional compound is higher than the molar ratio of hydroxy-functional compound to amine-functional compound.8. (canceled)9. The process of wherein the alkanolamine-functional compound and the carbon oxide delivering agent are at least partly added as one compound by using a carbamate adduct.10. The process of wherein the amine-functional compound and the carbon oxide delivering agent are at least partly added as one compound by using an urea adduct.11. The process of wherein the amine functional compound is a primary amine or a cyclic secondary amine compound.12. The process of wherein the amine-functional compound is of the formula R—NHand R is an alkyl group containing 6 to 22 carbon atoms13. The process of wherein next a step is performed to convert the obtained cyclic alkylene urea into its corresponding propylene amine.15. The process of wherein the hydroxy-functional compound claim 14 , the amine-functional compound do not contain cyclic units and react in the presence of water claim 14 , with a molar ratio of water:carbon oxide ...

Inhibition of olig2 activity

Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of Olig2. Also described herein are methods of using such Olig2 inhibitors, alone and in combination with other compounds, for treating cancer and other diseases. In particular the Olig2 inhibitors may be used to treat glioblastoma.

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.

4-(4-cyano-2-thioaryl)dihydropyrimidinones and use thereof

The present application relates to novel 4-(4-cyano-2-thioaryl)dihydro­pyrimidin-2-one derivatives, to processes for preparation thereof, to the use thereof alone or in combination for treatment and/or prevention of disorders, and to the use thereof for production of medicaments for treatment and/or prevention of disorders, especially for treatment and/or prevention of disorders of the lung and of the cardiovascular system.

ARYL-N-ARYL DERIVATIVES FOR TREATING A RNA VIRUS INFECTION

A compound of formula (Ic) 114.-. (canceled)16. A compound of formula (Ic) according to claim 15 , wherein the divalent 5-membered heteroaromatic ring comprising 1 claim 15 , 2 claim 15 , 3 or 4 heteroatoms is selected from a triazole claim 15 , an imidazole claim 15 , a tetrazole and an oxadiazole.18. A compound of formula (Ic) according to claim 15 , wherein{'sub': g', 'h', '1', '4, 'Ris a hydrogen atom and Rrepresents a hydrogen atom or a (C-C)alkyl group,'}or any of its pharmaceutically acceptable salt.19. A compound of formula (Ic) according to claim 15 , wherein{'sup': '2', 'claim-text': [{'sub': k', 'k, 'a —CO—NR— group, wherein Rrepresents a hydrogen atom or a methyl group,'}, 'a —NH—CO— group', 'a —O— group,', 'a —CO— group,', 'a —CH(OH)— group,', {'sub': '2', 'a —SO— group,'}, 'a —NH— group,', {'sub': '2', 'a NH—SO—,'}, 'a divalent 5-membered heteroaromatic ring comprising 1, 2, 3 or 4 heteroatoms,'}, 'or', {'sub': '2', 'a —SO—NH— group,'}], 'Xrepresents'}or any of its pharmaceutically acceptable salt.20. A compound of formula (Ic) according to claim 19 , wherein the divalent 5-membered heteroaromatic ring comprising 1 claim 19 , 2 claim 19 , 3 or 4 heteroatoms is selected from a triazole claim 19 , an imidazole claim 19 , a tetrazole and an oxadiazole.22. A compound of formula (Ic) according to claim 15 , wherein [{'sub': 1', '4', '2, 'a (C-C)alkyl group, optionally interrupted by a —SO— group or a —SO— group,'}, {'sub': 3', '6, 'a (C-C)cycloalkyl group,'}, 'a trifluoromethyl group, or', 'a halogen atom,, 'R and R′ independently represent'}or any of its pharmaceutically acceptable salt.26. A method of treating and/or preventing RNA virus infection caused by a RNA virus belonging to group IV or V of the Baltimore classification comprising the administration to patient in need thereof of a therapeutically effective quantity of a compound of formula (Ic) according to or any of its pharmaceutically acceptable salts.27. A method of treating and/or preventing ...

Pharmaceutical composition for treatment of alzheimer's disease

Disclosed is a pharmaceutical composition for treatment of Alzheimer's disease, which contains a compound represented by the formula (I) below, a pharmaceutically acceptable salt thereof, or a solvate of any of them as an active ingredient. (I) (In the formula, ring A represents an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E represents a lower alkylene or the like; X represents S, O or NR1 wherein R1 represents a hydrogen or a lower alkyl; R2a, R2b, R3a, R3b, R4a and R4b independently represent a hydrogen, a halogen, a hydroxy or the like; n and m independently represent an integer of 0-3 and n + m is within the range of 1-3; and R5 represents a hydrogen, an optionally substituted lower alkyl or the like.)

環式ｎ，ｎ’−ジアリールチオ尿素及びｎ，ｎ’−ジアリール尿素−アンドロゲン受容体アンタゴニスト、抗癌剤、その調製のための方法及び使用

Quinazoline derivatives, process for their preparation and their use as anti-cancer agents

Substituted 1-aminoalkyllactams and their use as muscarinic receptor antagonists

This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula I: wherein X, Y, and Z are O, S or NR<SUP>5</SUP>, and the other substituents are as defined in the specification; and prodrugs, individual isomers, racemic or non-racemic mixtures of isomers, and pharmaceutically acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use as therapeutic agents.

Dihüdropürimidiinid ja nende kasutamine

유기막 형성 재료, 유기막 형성 방법, 패턴 형성 방법 및 화합물

[과제] 드라이 에칭 내성을 가짐과 더불어 고도의 매립/평탄화 특성/기판과의 밀착력을 더불어 갖는 유기막을 형성하기 위한 유기막 형성 재료를 제공하는 것을 목적으로 한다. [해결수단] 하기 일반식 (1)로 표시되는 화합물 및 유기 용제를 포함하는 것을 특징으로 하는 유기막 형성 재료. (상기 일반식 (1) 중, X는 탄소수 2∼50의 n가의 유기기 또는 산소 원자이고, n은 1∼10의 정수이고, R 1 은 독립적으로 하기 일반식 (2) 중 어느 하나이다.) (상기 일반식 (2) 중, 파선은 X에의 결합 부위를 나타내고, Q 1 은 카르보닐기를 함유하는 1가의 유기기로서, 적어도 일부는 하기 일반식 (3)으로 표시되는 기이다.) (상기 일반식 (3) 중, 파선은 결합 부위를 나타내고, X1은 단일 결합 또는 탄소수 1∼20의 2가의 유기기를 나타내며, 이 유기기가 방향환을 갖는 경우는 치환기를 갖더라도 좋다. R 2 는 수소 원자, 메틸기, 에틸기 또는 페닐기를 나타낸다. **는 결합 부위를 나타낸다.)

4-(4-氰基-2-硫代芳基)二氢嘧啶酮和它们的使用

本发明涉及新的4-(4-氰基-2-硫代芳基)二氢嘧啶-2-酮衍生物，它们的制备方法，它们单独地或者结合地用于治疗和/或预防疾病和它们对于制备用于治疗和/或预防疾病，特别是用于治疗和/或预防肺和心血管系统疾病的药物的应用。

Method for obtaining e-isomers of acrylic acid derivatives

Compounds of formula: <CHEM> and stereoisomers thereof, wherein the substituents have the meaning given in claim 1; and metal complexes thereof. The compounds are useful mainly as fungicides but also as plant growth regulators and insecticides/nematocides.

Substituted 1-aminoalkyl lactames, pharmaceutical composition based on thereof and method for their preparing

FIELD: organic chemistry, medicine. SUBSTANCE: invention describes a compound of the general formula (I): wherein R 1 , R 2 and R 3 mean independently in each case hydrogen, halogen atom, (C 1 -C 6 )-alkyl, -OR', -SR', -NR'R'', -SOR', -SO 2 R', -COOR', -OCOR', -OCONR'R'', -OSO 2 R', -OSO 2 NR'R'', -NR'SO 2 R''. -NR'COR'', -SO 2 NR'R'', -SO 2 (CH) 1-3 CONR'R'', -CONR'R'', cyano-group, halogenalkyl or nitro-group; or if R 1 and R 2 if there are adjacent then in common with carbon atom to which they are bound can form 5-7-membered aromatic, saturated or unsaturated cycle optionally comprising one or two ring heteroatoms taken among nitrogen atom (N), S(O) 0-2 or oxygen atom (O), and optionally substituted with (C-C 6 )-alkyl, halogen atom, cyano-group or (lower)-alkoxy-group; R' and R'' mean independently in each case hydrogen atom, (C 1 -C 6 )-alkyl, substituted (C 1 -C 6 )-alkyl, (C 0 -C 3 )-alkylalkoxy-group, aryl, heterocyclyl, heteroaryl, aryl-(C 1 -C 3 )-alkyl, heteroaryl-(C 1 -C 3 )-alkyl, heterocyclyl-(C 1 -C 3 )-alkyl, cycloalkylalkyl, cycloalkyl; or R' and R'' in common with nitrogen atom to which they are bound can form also 5-7-membered cycle optionally comprising one additional ring heteroatom taken among nitrogen (N), oxygen (O) atom or S(O) 0-2 ; in each case R 4 means (C 1 -C 6 )-alkyl; R 5 means independently in each case (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkenyl or cycloalkyl; one among X, Y or Z means independently -S-, -O-, -CH 2 - or ›N-R 6 and others mean -CH 2 -; R 6 means hydrogen atom, (C 1 -C 6 )-alkyl, halogen alkyl, aryl-(C 1 -C 6 )-alkyl, heteroaryl-(C 1 -C 6 )-alkyl, -(C 1 -C 6 )-CR'R'R', -COOR', -SO 2 R', -C(O)R', -SO 2 (CH 2 ) 0-3 -NR'R'', -CONR'R'', -C(O)OCH 2 OC(O)R', -C(O)-CH 2 -S-C(O)R' or PO(OR') 2 wherein R&# ...

Arylsulfonyl naphthalene derivatives and uses thereof

본 발명은 하기 화학식 I의 화합물 또는 이의 약학적으로 허용 가능한 염에 관한 것이다: The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: 화학식 I Formula I 상기 식에서, Where m은 0 내지 3이고; m is 0 to 3; q는 0 내지 3이고; q is 0 to 3; Ar은 임의적으로 치환된 아릴 또는 임의적으로 치환된 헤테로아릴이고; Ar is optionally substituted aryl or optionally substituted heteroaryl; R 1 및 R 7 은 각각 독립적으로 할로, 알킬, 할로알킬, 알콕시, 하이드록시, 헤테로알킬, 사이아노, -S(O)-R a , -C(=O)-NR b R c , -SO 2 -NR b R c , -N(R d )-C(=O)-R e 또는 -C(=O)-R f 이되, t는 0 내지 i이고, R a , R b , R c , R d 및 R e 는 각각 독립적으로 수소 또는 알킬이고, R f 는 수소, 알킬, 알콕시 또는 하이드록시이고; R 1 and R 7 are each independently halo, alkyl, haloalkyl, alkoxy, hydroxy, heteroalkyl, cyano, -S (O) -R a , -C (= O) -NR b R c , -SO 2 -NR b R c, -N ( R d) -C (= O) -R e , or -C (= O) -R f, and provided that, t is from 0 to i, R a, R b, R c, R d and R e are each independently hydrogen or alkyl, and R f is hydrogen, alkyl, alkoxy or hydroxy; R 2 는 이고; R 2 is ego; n은 1 내지 3이다. n is 1 to 3. 상기 화합물들은 5-하이드록시트립타민 6 및 2A 수용체 조절제이다. 또한, 화학식 I의 화합물의 제조방법, 이를 포함하는 조성물, 및 이의 사용 방법이 제공된다. The compounds are 5-hydroxytryptamine 6 and 2A receptor modulators. Also provided are methods of preparing the compounds of Formula I, compositions comprising the same, and methods of using the same.

METHOD OF OBTAINING ACCORDINGLY FIXED PHENACETHILGUANIDINE

有机膜形成材料、有机膜形成方法、图案形成方法、以及化合物

本发明涉及有机膜形成材料、有机膜形成方法、图案形成方法、以及化合物。本发明提供一种有机膜形成材料，其特征为包含下述通式(1)表示的化合物及有机溶剂。 该通式(1)中，X为碳数2～50的n价有机基团或氧原子，n为1～10的整数，R 1 独立地为下述通式(2)中任一者。 该通式(2)中，破折线表示键结到X的键结部位，Q 1 为含有羰基的1价有机基团，且至少一部分为下述通式(3)表示的基团。 该通式(3)中，破折线表示键结部位，X 1 表示单键、或碳数1～20的2价有机基团，且该有机基团具有芳香环时也可具有取代基。R 2 表示氢原子、甲基、乙基、或苯基。**表示键结部位。

New synthetic method of aryl iodides from aryl amines via a water-paste form

본 발명은 방향족 아민으로부터 방향족 요오드화물을 합성하는 신규의 방법에 관한 것으로, 유기용매 등을 사용하지 않고 최소량의 물만을 반응물에 첨가하여 물-반죽 상태에서 반응하여 최종생성물을 얻는 것을 특징으로 한다. 반응물로는 방향족 아민, NaNO 2 (또는 KNO 2 ), p -톨루엔 술폰산( p TsOH), KI(또는 NaI)가 사용된다. The present invention relates to a novel method for synthesizing aromatic iodides from aromatic amines, characterized in that the final product is obtained by reacting in a water-dough state by adding only a minimum amount of water to the reactants without using an organic solvent or the like. The reactants include aromatic amines, NaNO 2 (or KNO 2 ), p -toluene sulfonic acid ( p TsOH), KI (or NaI). 아민, 요오드 Amines, iodine

Antiviral compound and its purposes

本发明涉及∶(a)尤其抑制HCV的化合物和其盐；(b)可用于制备这种化合物和盐的中间体；(c)包含这种化合物和盐的组合物；(d)制备这种中间体、化合物、盐和组合物的方法；(e)使用这种化合物、盐和组合物的方法；和(f)包含这种化合物、盐和组合物的试剂盒。

Antiretroviral compounds and use thereof

FIELD: medicine. SUBSTANCE: invention refers to new compounds of formula (I) and their pharmaceutically acceptable salts, which inter alia inhibit hepatotropic hepatitis C virus and are applicable in treating hepatitis C virus. In formula (I) R 1 is specified in a group consisting of is specified in a group consisting of a carbon-carbon single bond and carbon-carbon double bond; R 5 , R 6 , R 11 , R 12 , R 13 and R 14 are independently specified in a group consisting of a hydrogen atom, methyl and a protective group for nitrogen specified in C 1-6 alkylsulphonyl; R 7 represents a hydrogen atom; R 2 is specified in a group consisting of a halogen atom, C 1-6 alkyl and heterocyclyl specified in 5-merous heteroaryl with 1-2 heteroatoms specified in nitrogen, oxygen and sulphur, wherein alkyl is optionally substituted by one or more substitute optionally specified in a group consisting of a halogen atom; and heterocyclyl is optionally substituted by C 1-3 alkyl; R 3 is specified in a group consisting of C 1-6 alkyl, C 2-4 alkenyl, C 1-6 alkyloxy and a halogen atom; L means a bond, and R 4 is specified in a group consisting of C 5 -C 6 -carbocyclyl, or R 4 means carbocyclyl with 2 condensed cycles specified in a group consisting of naphthalinyl, indenyl and dihydroindenyl, hexahydroindenyl, octahydroindenyl, wherein each can be substituted by a substitute specified in a group consisting of R E , R F and R J , and R E means hydroxy, oxo; R F means C 1-3 alkyl substituted by C 1-4 alkylsulphonylamino, imino, wherein imino is substituted by a C 1-4 alkylsulphonylamino group; and R J means an alkylsulphonylamino group; or L is specified in a group consisting of C(R A ) = C(R B ), wherein R A and R B mean a hydrogen atom, and R 4 is specified in a group consisting of C 6 carbocyclyl specified in phenyl substituted by R J having the above value. EFFECT: higher efficacy of the compound. 16 cl, 2 tbl, 52 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07C 15/58 C07D 239/54 C07D ...

The method of obtaining substituted

Этил 4-(5-бензоил-6-(4-(диэтиламино)фенил)-4-гидрокси-2-тиоксогексагидропиримидин-4-карбоксамино)бензоат, проявляющий анальгетическое и противовоспалительное действие

Изобретение относится к области органической химии, производным пиримидина, а именно, к этил 4-(5-бензоил-6-(4-(диэтиламино)фенил)-4-гидрокси-2-тиоксогексагидропиримидин-4-карбоксамино)бензоату (1) формулы:Технический результат: предложенное соединение проявляет анальгетическое и противовоспалительное действие, что позволяет использовать его в качестве анальгетического и противовоспалительного средства. 3 табл. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 717 246 C1 (51) МПК C07D 239/10 (2006.01) A61K 31/505 (2006.01) A61P 29/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 239/10 (2020.01); A61K 31/505 (2020.01); A61P 29/00 (2020.01); A61K 2121/00 (2020.01) (21)(22) Заявка: 2019118839, 17.06.2019 (24) Дата начала отсчета срока действия патента: Дата регистрации: 19.03.2020 (45) Опубликовано: 19.03.2020 Бюл. № 8 Адрес для переписки: 614990, г. Пермь, ул. Полевая, 2, ФГБОУ ВО ПГФА Минздрава России, патентный отдел C 1 (56) Список документов, цитированных в отчете о поиске: RU 2653511 С2, 10.05.2018. Фазылов С.Д. и др., Синтез и химическое превращения 4-(арил)-3,4-дигидропиримидин-(1Н)-2-тионов, Башкирский химический журнал, том 19, 2012, номер 5, стр. 9-14. WO 2013024447 A1, 21.02.2013. US 6469000 B1, 22.10.2002. R U (54) Этил 4-(5-бензоил-6-(4-(диэтиламино)фенил)-4-гидрокси-2-тиоксогексагидропиримидин-4карбоксамино)бензоат, проявляющий анальгетическое и противовоспалительное действие (57) Реферат: Изобретение относится к области органической химии, производным пиримидина, а именно, к этил 4-(5-бензоил-6-(4-(диэтиламино) ф е н и л ) - 4 - г и д р о к с и - 2 тиоксогексагидропиримидин-4-карбоксамино) бензоату (1) формулы: Технический результат: предложенное соединение проявляет анальгетическое и противовоспалительное действие, что позволяет использовать его в качестве анальгетического и Стр.: 1 C 1 2 7 1 7 2 4 6 (73) Патентообладатель(и): Федеральное государственное бюджетное образовательное учреждение ...

Phenylacetylene derivatives having an affinity for the MGLUR 5 receptor

1. Соединение формулы (I) ! ! в которой ! R1 обозначает водород или С1-С4алкил и ! R2 обозначает незамещенный или замещенный гетероцикл, или ! R1 обозначает водород или С1-С4алкил и ! R2 обозначает арил или замещенный арил, или ! R1 и R2 совместно с атомом азота образуют незамещенный или замещенный гетероцикл; ! R3 обозначает (С1-С4)алкил, (С1-С4)алкоксигруппу, трифторметил, галоген, цианогруппу, нитрогруппу, -СНО, -СОО(С1-С4)алкил, -СО(С1-С4)алкил; ! n равно 0, 1, 2, 3, 4 или 5; ! R4 обозначает ОН и ! R5 и R6 обозначают Н или С1-С4алкил, или ! R4 и R5 образуют связь и ! R6 обозначает Н или С1-С4алкил, или ! R4 и R6 образуют связь и ! R5 обозначает Н или С1-С4алкил, ! в форме свободного основания или соли присоединения с кислотой. ! 2. Соединение формулы (I') ! ! в которой R1, R2, R3 являются такими, как определено в п.1. ! 3. Соединение формулы (II) ! ! в которой R6, R5, R3, n являются такими, как определено в п.1. ! 4. Способ получения соединения формулы (I) по п.1 или его соли, который включает стадии ! а) получения соединения формулы (I), в которой i) R4 обозначает гидроксигруппу, ! R1 обозначает водород или С1-С4алкил и R2 обозначает незамещенный или замещенный гетероцикл или ii) R1 обозначает водород или С1-С4алкил и R2 обозначает арил или замещенный арил, с помощью восстановительного аминирования соединения формулы (II) ! ! в которой R6, R5, R3, n являются такими, как определено выше, соединением формулы (III) ! ! в которой R1 и R2 являются такими, как определено выше, или ! b) получения соединения формулы (I), в которой R4 обозначает гидроксигруппу, R1 и R2 совместно с атомом азота образуют незамещенный или замещенный гетероцикл, с помощью циклоконденсации соединения формулы (IV) ! ! или ! с) получения соединения формулы (I), в которо (19) РОССИЙСКАЯ ФЕДЕРАЦИЯ RU (11) 2007 143 507 (13) A (51) МПК C07C 211/52 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21), (22) Заявка: 2007143507/ ...

Производные пиперидин-2-она и фармацевтические композиции, содержащие такие соединения в качестве активного ингредиента

ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (51) ÌÏÊ 7 (11) 2004 118 719 (13) A C 07 D 211/76 ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÇÀßÂÊÀ ÍÀ ÈÇÎÁÐÅÒÅÍÈÅ (21), (22) Çà âêà: 2004118719/04, 21.11.2002 (71) Çà âèòåëü(è): ÎÍÎ ÔÀÐÌÀÑÜÞÒÈÊÀË ÊÎ., ËÒÄ. (JP) (30) Ïðèîðèòåò: 22.11.2001 JP 2001-357348 (43) Äàòà ïóáëèêàöèè çà âêè: 27.03.2005 Áþë. ¹ 9 (74) Ïàòåíòíûé ïîâåðåííûé: Åãîðîâà Ãàëèíà Áîðèñîâíà (86) Çà âêà PCT: JP 02/12174 (21.11.2002) Àäðåñ äë ïåðåïèñêè: 129010, Ìîñêâà, óë. Á.Ñïàññêà , 25, ñòð.3, ÎÎÎ "Þðèäè÷åñêà ôèðìà Ãîðîäèññêèé è Ïàðòíåðû", ïàò.ïîâ. Ã.Á. Åãîðîâîé (54) ÏÐÎÈÇÂÎÄÍÛÅ ÏÈÏÅÐÈÄÈÍ-2-ÎÍÀ È ÔÀÐÌÀÖÅÂÒÈ×ÅÑÊÈÅ ÊÎÌÏÎÇÈÖÈÈ, R U Ôîðìóëà èçîáðåòåíè 1. Ïðîèçâîäíîå ïèïåðèäèí-2-îíà, ïðåäñòàâëåííîå ôîðìóëîé (I) A 2 0 0 4 1 1 8 7 1 9 A ÑÎÄÅÐÆÀÙÈÅ ÒÀÊÈÅ ÑÎÅÄÈÍÅÍÈß Â ÊÀ×ÅÑÒÂÅ ÀÊÒÈÂÍÎÃÎ ÈÍÃÐÅÄÈÅÍÒÀ ãäå êîëüöî À ïðåäñòàâë åò (Ñ5-10)-ìîíî- èëè áèêàðáîöèêëè÷åñêîå êîëüöî èëè 5-10-÷ëåííîå ìîíî- èëè áèãåòåðîöèêëè÷åñêîå êîëüöî ñ 1-5 àòîìàìè àçîòà, 1-2 àòîìàìè êèñëîðîäà è/èëè àòîìîì ñåðû; R 1 ïðåäñòàâë åò (1) (Ñ1-8)-àëêèë, (2) (Ñ2-8)-àëêåíèë, (3) (Ñ2-8)-àëêèíèë, (4) àòîì ãàëîãåíà, (5) -OR 4, (6) -NR 5R 6, Ñòðàíèöà: 1 RU 2 0 0 4 1 1 8 7 1 9 (87) Ïóáëèêàöè PCT: WO 03/04398 (30.05.2003) R U (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 22.06.2004 (72) Àâòîð(û): ÒÀÊÀÕÀÑÈ Êàíäçè (JP), ßÌÀÌÎÒÎ Ñèíãî (JP), ÍÀÊÀ Ìàñàî (JP) A 2 0 0 4 1 1 8 7 1 9 A R U 2 0 0 4 1 1 8 7 1 9 Ñòðàíèöà: 2 R U (7) -NR 7COR 8, (8) -CONR 9R 10, (9) -COOR 11, (10) -SO2NR 12R 13, (11) -NR 14SO2R 15, (12) -SR 16, (13) -S(O)R 17, (14) -SO2R 18, (15) -NR 22COOR 23, (16) -NR 24CONR 25R 26, (17) -COR 27, (18) -NO2, (19) -CN, (20) -CF3, (21) -OCF3, (22) Ñóñ1 èëè (23) (Ñ1-8)-àëêèë, (Ñ2-8)-àëêåíèë èëè (Ñ2-8)-àëêèíèë, çàìåùåííûé 1-5 çàìåñòèòåë ìè, âûáðàííûìè èç ãðóïïû, ñîñòî ùåé èç (à) àòîìà ãàëîãåíà, (b) -OR 4, (c) -NR 5R 6, (d) -NR 7COR 8, (e) -CONR 9R 10, (f) -COOR 11, (g) -SO2NR 12R 13, (h) -NR 14SO2R 15, (i) -SR 16, (j) -S(O)R 17, (k) -SO2R 18, (l) -NR 22COOR 23, (m) -NR 24CONR 25R ...

Application of pyrimidylamino-benzamide derivatives for the treatment of fibrosis

1. Применение пиримидиламинобензамида формулы I ! , ! где (а) Ру обозначает 3-пиридил, ! R1 обозначает водород, (низш.)алкил, (низш.)алкокси(низш.)алкил, ацилокси(низш.)алкил, карбокси(низш.)алкил, (низш.)алкоксикарбонил(низш.)алкил или фенил(низш.)алкил, ! R2 обозначает водород, (низш.)алкил, необязательно замещенный одним или более одинаковых или различных радикалов R3, циклоалкил, бензоциклоалкил, гетероциклил, арильную группу или моно- или бициклическую гетероарильную группу, не содержащую или содержащую в цикле 1, 2 или 3 атома азота, и не содержащую или содержащую 1 атом кислорода, а также не содержащую или содержащую 1 атом серы, при этом указанные группы в каждом случае не содержат заместителей или являются моно- или полизамещенными, и ! R3 обозначает гидроксигруппу, (низш.)алкоксигруппу, ацилоксигруппу, карбоксигруппу, (низш.)алкоксикарбонил, карбамоил, N-моно- или N,N-дизамещенный карбамоил, аминогруппу, моно- или дизамещенную аминогруппу, циклоалкил, гетероциклил, арильную группу или моно- или бициклическую гетероарильную группу, не содержащую или содержащую в цикле 1, 2 или 3 атома азота и не содержащую или содержащую 1 атом кислорода, а также не содержащую или содержащую 1 атом серы, при этом указанные группы в каждом случае не содержат заместителей или являются моно- или полизамещенными, или где ! R1 и R2 вместе обозначают алкилен, содержащий четыре, пять или шесть атомов углерода, необязательно моно- или дизамещенный (низш.)алкилом, циклоалкилом, гетероциклилом, фенилом, гидроксигруппой, (низш.)алкоксигруппой, аминогруппой, моно- или дизамещенной аминогруппой, оксогруппой, пиридилом, пиразинилом или пиримидинилом; бензалкил� РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2011 105 059 (13) A (51) МПК A61K 31/506 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2011105059/15, 14.07.2009 (71) Заявитель(и): НОВАРТИС АГ (CH) Приоритет(ы): (30) Конвенционный приоритет: 14.07.2008 EP 08160366.4 (85) Дата начала ...

Substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors

This invention relates to substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors, to pharmaceutical compositions comprising such compounds, and to methods of using these compounds for treating viral infection. A representative compound of the invention is the compound of formula: ##STR1## wherein R 22 and R 23 are allyl.

Substituted 1-aminoalkyl-lactams compound and their use as muscarinic receptor antagonists

本发明涉及通常是M2/M3毒蕈碱受体拮抗剂的通式(I)化合物，其中X、Y或Z当中有一个独立地为-S-、-O-、-CH 2 -或＞N-R 4 ，其它的为-CH 2 -；p是0-3并包括0和3的整数；m是0-3并包括0和3的整数；n是1-6并包括1和6的整数；R 3 是(C 1-6 )-烷基、(C 1-6 )-链烯基、(C 1-6 )-炔基或环烷基；且R 1 、R 2 和R 3 是氢或特定的取代基。这些化合物可用于治疗与平滑肌障碍有关的疾病。

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

Aminodihydrothiazine derivative

A composition having BACE 1 inhibitory activity containing a compound represented by the general formula (I): wherein ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E is lower alkylene; X is S, O, or NR 1 ; R 1 is a hydrogen atom or lower alkyl; R 2a , R 2b , R 3a , R 3b , R 4a and R 4b is each independently a hydrogen atom, halogen, or hydroxy etc.; n and m are each independently an integer of 0 to 3; n+m is an integer of 0 to 3; R 5 is a hydrogen atom or substituted lower alkyl; its pharmaceutically acceptable salt, or a solvate thereof.

Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 9 , ring A, ring B, m, n, p, -L 1 -,L 2 -, and L 3 - is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed.

Cyclic guanidine ionic liquid

본 발명은 보다 넓은 전위 범위에서 안정적이며, 높은 이온 전도성을 가지는 이온 액체를 제공한다. 이 이온 액체는 하기 식 (1)로 표시되는 환상 구아니딘 염으로 이루어진다. The present invention provides an ionic liquid which is stable in a wider potential range and has a high ion conductivity. This ionic liquid is composed of a cyclic guanidine salt represented by the following formula (1). 식 중, R 1 및 R 2 는 독립적으로 알킬기 또는 알콕시알킬기를 나타내고, X는 메틸렌기, 산소 원자, 유황 원자 또는 R 3 N을 나타낸다. R 3 은 알킬기, 알콕시알킬기 또는 아실기를 나타낸다. l, m, n은 1 이상 6 이하의 정수를 나타낸다. Y - 는 (R 4 SO 2 ) 2 N - , R 4 SO 3 - , R 4 COO - , BF 4 - , PF 6 - , NO 3 - , (CN) 2 N - , (CHO) 2 N - , NCS - , R 4 OSO 3 - , R 4 SO 2 S - , 및 할로겐 이온 등의 1가의 음이온을 나타낸다. 이 이온 액체는 각종 전해질로서 유용하며, 특히 전기화학 셀의 전해질로서 유용하다. In the formula, R 1 and R 2 independently represent an alkyl group or an alkoxyalkyl group, and X represents a methylene group, an oxygen atom, a sulfur atom or R 3 N. R 3 represents an alkyl group, an alkoxyalkyl group or an acyl group. l, m and n represent an integer of 1 or more and 6 or less. Y - is (R 4 SO 2) 2 N -, R 4 SO 3 -, R 4 COO -, BF 4 -, PF 6 -, NO 3 -, (CN) 2 N -, (CHO) 2 N -, NCS -, R 4 OSO 3 - , R 4 SO 2 S -, and a monovalent anion such as halogen ion. This ionic liquid is useful as various electrolytes, and is particularly useful as an electrolyte of an electrochemical cell. 환상, 구아니딘, 요소, 양이온, 음이온, 전해질, 전기화학 셀 Cyclic, guanidine, urea, cation, anion, electrolyte, electrochemical cell

Cyclic urea and carbamate inhibitors of 11β-hydroxysteroid dehydrogenase 1

Substituted 1-aminoalkyl-lactams and their use as muscarinic receptor antagonists

본 발명은 일반적으로 무스카린성 M2/M3 수용체 길항제로서 하기 화학식 I의 화합물에 관한 것이다: 화학식 I 상기 식에서, X, Y 또는 Z중 하나는 독립적으로 -S-, -O- 또는 >N-R 4 이고 나머지 둘은 -CH 2 -이고; p는 0 내지 3의 정수이고; m은 0 내지 3의 정수이고; n은 1 내지 6의 정수이고; R 3 은 (C 1-6 )-알킬, (C 1-6 )-알케닐, (C 1-6 )-알키닐 또는 사이클로알킬이고; R 1 , R 2 및 R 3 은 수소 또는 특정한 치환체이다. 상기 화합물은 평활근 장애와 관련된 질병을 치료하는데 유용하다.

Pesticidal compounds

The present invention relates to the compounds of formula (I), and the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof wherein the variables are defined according to the description. The compounds of formula (I), as well as the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof, are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

Piperidin-2-one derivative compounds and drugs containing these compounds as the active ingredient

本发明提供一种由式(I)(其中所有符号的描述参见说明书)表示的哌啶－2－酮衍生化合物或其无毒性盐；式(I)化合物抑制p38MAP激酶的激活并可用于预防和/或治疗多种炎性疾病、风湿性关节炎、骨关节炎、关节炎、骨质疏松症、自身免疫性疾病、传染病、脓毒症、恶病质、脑梗塞、阿尔茨海默氏病、哮喘、慢性肺炎性疾病、再灌注损伤、血栓症、血管球性肾炎、糖尿病、移植－宿主排斥、炎性肠病、克罗恩氏病、溃疡性结肠炎、多发性硬化、肿瘤的生长与转移、多发性骨髓瘤、浆细胞白血病、Castleman疾病、心房粘液瘤、银屑病、皮炎、痛风、成人呼吸窘迫综合征(ARDS)、动脉硬化、经皮透照冠状动脉血管成形术(PTCA)后的再狭窄或胰腺炎。

Cyclic n,n'-diarylthioureas or n,n'-diarylureas - antagonists of androgen receptors, anti-cancer medication, method of obtaining and application

FIELD: medicine, pharmaceutics. ^ SUBSTANCE: claimed invention relates to novel cyclic N,N'-diarylthioureas or N,N'-diarylureas of general formula (1), their optic (R)- and (S)-isomers and their pharmaceutically acceptable salts - antagonists of androgenic receptors. In formula (1), where: X represents oxygen or sulfur atom; m=0 or 1, mR1 represents C1-C3alkyl; R2 and R3 represent hydrogen atom; or R2 and R3 together with carbon atom, to which they are bound, form group C=O; or represents group NH; R4 and R5 represent hydrogen atom; or R4 represents hydrogen atom, and R5 represents methyl; or R4 represents hydrogen atom, methyl, and R5 represents group Zn-Y-R6, in which n=1 or 2, Z represents CH2 or C=0 and Y- oxygen atom or N-CH3, or Y represents C=O, and Z represents CH2; R6 represents hydrogen atom, methyl, benzyl, hydroxygroup or R5 and R4 together with atoms, to which they are bound, form five or sic-member heterocycle, including, at least, oxygen or nitrogen atom, which can be substituted by methyl. Invention also relates to method of obtaining compounds. ^ EFFECT: invention relates to anti-cancer substance, pharmaceutical composition, medication and method of treating prostate cancer with application of invention compounds. ^ 12 cl, 6 dwg, 16 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07C C07D C07D C07D C07D A61K ФЕДЕРАЛЬНАЯ СЛУЖБА A61K ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, A61K ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ A61K A61K (12) ОПИСАНИЕ 2 434 851 275/32 (2006.01) 233/86 (2006.01) 233/56 (2006.01) 471/10 (2006.01) 491/107 (2006.01) 31/27 (2006.01) 31/513 (2006.01) 31/4166 (2006.01) 31/4188 (2006.01) 31/527 (2006.01) (13) A61P 35/00 C1 (2006.01) ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2010130618/04, 22.07.2010 (24) Дата начала отсчета срока действия патента: 22.07.2010 (72) Автор(ы): Иващенко Александр Васильевич (RU), Митькин Олег Дмитриевич (RU) (45) Опубликовано: 27.11.2011 Бюл. № 33 C 1 2 4 3 4 8 5 1 R U C 1 Адрес для переписки: 141400, Московская обл., г. ...

New preparation of 2-(2-n-butyl-4-hydroxy-6-methyl-pyrimidin-5-yl)-N,N-dimethylacetamide

본 발명은 하기 [화학식 2] 화합물과 펜탄아미딘(pentanamidine) 또는 그의 염을 염기 존재하에 반응시켜 2-(2-n-부틸-4-히드록시-6-메틸-피리미딘-5-일)-N,N-디메틸 아세트아미드를 제조하는 방법을 제공한다. [화학식 2] 상기 식에서, R 1 은 C 1 ~C 6 인 직쇄 또는 측쇄 알킬이거나 C 3 ~C 6 인 시클로 알킬이다.

Substituted aryloxyalkyldiamines possessing vasoconstrictiv activity

Настоящее изобретение относится к области медицины, может быть использовано при получении лекарственного средства для лечения мигрени и касается применения соединений общей формулы I для получения лекарственного средства для лечения состояний, связанных с расширением сосудов, в частности мигрени, новых соединений формулы I, способа их получения, фармацевтической композиции, содержащей указанные соединения, и способа ее получения. Изобретение позволяет получить лекарственный препарат, обладающий повышенной сосудосуживающей активностью. 4 с. и 6 з.п.ф-лы, 6 табл. Эс ‘с ПЧ сэ (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 13) ВИ “” 2 158 126 ^С2 57 МК’ А 64 К 31/506, 31/501, С 070 239/42, А 61Р 25/06 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 96105988/14, 12.08.1994 (24) Дата начала действия патента: 12.08.1994 (30) Приоритет: 19.08.1993 ЕР 93202445.8 19.08.1993 ОЕ 93202444.1 (46) Дата публикации: 27.10.2000 (56) Ссылки: Ц$ 4593039 А, 1986. ЕР 0511072 А, 1992. ЕА 0042593 А, 1981. МД.МАШКОВСКИЙ. Лекарственные средства. - М.: Медицина, 1986, ч.1, с.274 - 276. (85) Дата перевода заявки РСТ на национальную фазу: 19.03.1996 (86) Заявка РСТ: ЕР 94/02702 (12.08.1994) (87) Публикация РСТ: М/О 95/05366 (23.02.1995) (98) Адрес для переписки: 129010, Москва, ул. Большая Спасская 25, стр.3, ООО "Городисский и Партнеры", Лебедевой Н.Г. (71) Заявитель: ЖАНСЕН ФАРМАСЕТИКА Н.В. (ВЕ) (72) Изобретатель: Ги Розали Эжен ВАН ЛОММЕН (ВЕ), Марсель Франс Леопольд ДЕ БРЮИН (ВЕ) ‚ Пит Том Берт Пауль ВИГЕРИНК (ВЕ) (73) Патентообладатель: ЖАНСЕН ФАРМАСЕТИКА Н.В. (ВЕ) (54) ЗАМЕЩЕННЫЕ АРИЛОКСИАЛКИЛДИАМИНЫ, ОБЛАДАЮЩИЕ СОСУДОСУЖИВАЮЩИМ ДЕЙСТВИЕМ (57) Настоящее изобретение относится к области медицины, может быть использовано при получении лекарственного средства для лечения мигрени и касается применения соединений общей формулы | для получения лекарственного средства для лечения состояний, связанных с расширением сосудов, в частности мигрени, новых соединений ...

Acrylic acid ester derivative, manufacture and agricultural drug composition

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

Substituted heterocyclic compounds, methods of their synthesis, intermediate compounds, method of control over weeds

FIELD: organic chemistry, heterocyclic compounds. SUBSTANCE: invention relates to substituted heterocyclic compounds of the formula (I) where E - oxygen or sulfur; A means CR 3 or N; R 3 - hydrogen or lower alkyl; D completes 5- or 6-membered nonaromatic heterocyclic ring that has optionally additional heteroatoms taken from oxygen, nitrogen or sulfur and can be substituted with C 1-10 -alkyl or phenyl; R 1 and R 2 - hydrogen, alkyl, alkenyl, alkynyl, cyclopropyl, cyclopropylmethyl, cyclohexyl, adamantyl, phenyl or pyridyl; or R 1 and R 2 together with nitrogen atom to which they are bound form morpholine ring; Z - halogen, cyano-group, NHOH, SF 5 , acylamino-group, COOR 7 , NR 13 R 14 , dibenzylaminosulfonyl; or Z - alkyl, alkenyl, alkoxy, phenoxy, alkylthio, alkylsulfonyl or CO-alkyl and each group can be substituted with halogen or C 1-6 -alkoxy- -group; R 7 is C 1-10 -alkyl; R 13 and R 14 - hydrogen or SO 2 --alkyl; m = 0, 1 or 2. Compounds of the formula (I) show activity against broad order of weeds including monocotyledonous and dicotyledonous species. EFFECT: improved method of synthesis, enhanced effectiveness of compounds. 15 cl, 9 dwg, 17 tbl, 102 ex о509есгс пы Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) 13) ВО "2 125 050 ^^ С1 5 МК С 070 277/14, 207/273, 211/76, 233/38, 239/10, 261/04, 265/02, 265/32, 279/12, 285/16, 417/12, А 01 М 43/84, 43/78, 43/50, 43/40, 43/36, 43/54 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 95113593/04, 16.11.1993 (30) Приоритет: 04.12.1992 СВ 9225377.2 (46) Дата публикации: 20.01.1999 (71) Заявитель: Зенека Лимитед (СВ) (72) Изобретатель: Ян Тревор Кей (СВ), Джон Эдвард Дункан Бартон (СВ), Дэвид Джон Коллинз (СВ), Богдан Ковальчик (СВ), Глинн (56) Ссылки: ЕР 0200415 АТ, 1986. ЗИ 1071624 А, Митчелл (СВ), Джон Мартин Шриббз (93), Джон 1984. $Ц 819102 А, 1951. $Ц 750989 А, 1981. Майкл Кокс (СВ), Найджел Джон Барнз ЗИ 584739 А, 1977. 30 921448 А, 1982. ЗИ (СВ), Стивен Кристофер Смит (СВ ...

Novel peptide derivatives

본 발명은 일반식(I):A 1 -A 2 -NH-(CH 2 ) n -B 및 일반식(V): A 1 -A 2 -NH-(CH 2 ) n -B-D에 따른, 트립신형 세린 프로테아제의 신규한 경쟁적인 억제제, 그의 합성 방법, 유효 성분으로서 이들 화합물을 함유하는 제약 조성물, 및 관련 질환의 예방 및 치료를 위한 트롬빈 억제제, 항응고제 및 항염 억제제로서의 이들 화합물의 용도에 관한 것이다. 상기 식 중, A 1 은 하기 일반식(IIa),(IIb), (IIc), (IId) 또는 (IIe)의 구조 단편을 나타내고, A 2 는 하기 일반식(IIIa), (IIIb) 또는 (IIIc)의 구조 단편을 나타내고, B는 하기 일반식(IVa), (IVb), (IVc) 또는 (IVd)의 구조 단편을 나타낸다. 또한 본 발명은 신규 화합물, 화합물의 신규 농도 및 특히 제약 화합물의 합성을 위한 신규 구조 단편에 관한 것이다. The present invention of the general formula (I): A 1 -A 2 -NH- (CH 2) n -B , and the general formula (V): A 1 -A 2 -NH- (CH 2), according to the trip n -BD To pharmaceutical compositions containing these compounds as active ingredients, and to the use of these compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents for the prophylaxis and treatment of related disorders. In the formula, A 1 is represented by the following general formula (IIa), (IIb), (IIc), (IId) or represents a structural fragment of (IIe), it is represented by the following general formula (IIIa) A 2, (IIIb ) or ( IIIc), and B represents a structural fragment of the following general formula (IVa), (IVb), (IVc) or (IVd). The present invention also relates to novel compounds, novel concentrations of compounds and novel structural fragments, in particular for the synthesis of pharmaceutical compounds.

Amidino derivatives useful as nitric oxide synthase inhibitors

본 발명은 산화질소 신타제 저해제로서 유용한 아미디노유도체를 함유하는 유용한 의약 조성물을 개시하고 있다.

The method of obtaining sulfonyl compounds

Aminodihydrothiazine derivatives

FIELD: chemistry. SUBSTANCE: described is a composition with inhibitory activity on BACE1, which contains a compound of general formula (I), where ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E denotes a lower alkylene; X is S, O or NR 1 ; R 1 denotes a hydrogen atom or lower alkyl; each R 2a , R 2b , R 3a , R 3b , R 4a and R 4b independently denotes a hydrogen atom, an optionally substituted alkyl or optionally substituted carbocyclic group; each n and m independently denotes an integer from 0 and 3; n+m equals an integer from 1 to 3; R 5 denotes a hydrogen atom or an optionally substituted lower alkyl; a pharmaceutically acceptable salt or solvate thereof. Described also is a compound of formula (I) and a pharmaceutical composition. EFFECT: highly effective treatment. 21 cl, 170 tbl, 4 ex 2416603 С9 ко РОССИЙСКАЯ ФЕДЕРАЦИЯ 7 ВУ” 2416 603” 9 (51) МПК С07О 2394 (2006.01) Аб1К 31/541 (2006.01) С07О 239/24 (2006.01) Аб1К 3155 (2006.01) С07О 265/08 (2006.01) Аб1К 31054 (2006.01) С07О 277/8 (2006.01) Аб1Р 25/28 (2006.01) | С07О 27906 (2006.01) С07О 279008 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА С07Р 25102 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ: А6/К 31/426 (2006.01) ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ Аб1К 31/505 (2006.01) Аб1К 31/54 (2006.01) 12) СКОРРЕКТИРОВАННОЕ ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ Примечание: библиография отражает состояние при переиздании (21)(22) Заявка: 2008120601/04, 23.10.2006 (24) Дата начала отсчета срока действия патента: 23.10.2006 Приоритет(ь): (30) Конвенционный приоритет: 25.10.2005 ]Р 2005-309642 20.03.2006 )Р 2006-076636 (43) Дата публикации заявки: 10.12.2009 Бюл. № 34 (45) Опубликовано: 20.04.2011 (15) Информация о коррекции: Версия коррекции №1 (\М1ТС2) (48) Коррекция опубликована: 27.07.2011 Бюл. № 21 (56) Список документов, цитированных в отчете о поиске: ]Р 8231521 А, 10.09.1996. УГО 2004014843 АТ, 19.02.2004. ]Р 2005-509651 А, 14.04.2005. 0$ 2005165080 АТ, 28.07.2005. }Р 2005-517634 А, 05.06. ...

Hydroxysteroid dehydrogenase inhibitors

Compounds, pharmaceutical compositions, kits and methods are provided for use with hydroxysteroid dehydrogenases that comprise a compound selected from the group consisting of: formula (I), wherein the variables are as defined herein.

Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid derivatives as integrin antagonists.

La presente invencion se refiere a una clase de compuestos representado por la formula (I): (Ver Formula) o una sal de los mismos farmacéuticamente aceptable; en donde A es (a) o (b) o (c) o (d): (Ver Formula) a composiciones farmacéuticas de los mismos y a métodos para usar estos compuestos y esas composiciones como antagonistas de la integrina alfav beta3.

Cyclic ureas, method of inhibition of retrovirus growth and pharmaceutical composition

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention describes new cyclic derivatives of urea of the general formula (I) where values W, R 4 ,R 4Δ ,R 5 ,R 6 ,R 7 ,R 7Δ and n are given in p. 1 of the invention claims. Synthesized compounds can be used as inhibitors of retroviral protease activity. Invention describes a pharmaceutical composition based on compounds of the formula (I) and a method of inhibition of retrovirus growth using compounds of the formula (I). EFFECT: enhanced inhibitory activity of compounds. 20 cl, 2 tbl, 22 ex ОС ГС ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) ВИ” 2131 420. (51) МПК 13) СЛ 413/06, 4413/14, 239/10, А б1 К 31/505, 31/55 С 070 243/04, 401/06, 401/14, 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 94031126/04, 13.10.1992 (30) Приоритет: 11.10.1991 1$ 07/776,491 15.05.1992 1$ 07/883,944 29.09.1992 ЦЗ 07/953,272 (46) Дата публикации: 10.06.1999 (56) Ссылки: ЕР 0248220 АЗ, 1987. ЕР 0249136, 1987. 5Ц 593666, 1978. 50 1435139 АЗ, 1988. \М/О 91101326, 1991. ЕР 0336466, 1989. ЕР 0384522, 1990. КЦ 2031496, 19.06.95. (85) Дата перевода заявки РСТ на национальную фазу: 08.04.94 (86) Заявка РСТ: 1$ 9208749 (13.10.92) (87) Публикация РСТ: М/О 9307128 (15.04.93) (98) Адрес для переписки: 129010, Москва, ул.Б.Спасская, д.25, стр.3, ООО "Союзпатент" (71) Заявитель: Дзе Дюпон Мерк Фармасьютикал Компани (ЦЗ) (72) Изобретатель: Патрик Юк-Сун Лэм (ЦЗ), Чарльз Джозеф Айрмэнн (ЦЗ), Карл Николас Ходж (4$), Прабхакар Кондаджи Джадхав (0$), Джордж Винсент Делукка (ЦЗ) (73) Патентообладатель: Дзе Дюпон Мерк Фармасьютикал Компани (Ц$) (54) ЦИКЛИЧЕСКИЕ МОЧЕВИНЫ, СПОСОБ ИНГИБИРОВАНИЯ РОСТА РЕТРОВИРУСОВ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ (57) Реферат: Описываются новые — циклические мочевины общей формулы //, где значения М! В“. В4^ ВЗ В6б В’ В’^ и п описаны в п. 1 формулы, пригодные в качестве ингибиторов протеазы ретровирусов. Описываются фармацевтическая композиция на основе соединений формулы //, а также способ ...

Aspartate ester inhibitors of interleukin-1.beta. converting enzyme

The present invention relates to compounds that are inhibitors of interleukin-1.beta. converting enzyme that have formula (I). This invention also relates to a method of treatment of stroke, inflammatory diseases, reperfusion injury, Alzheimer's disease, and shigellosis, and to a pharmaceutically acceptable composition that contains a compound that is an inhibitor of interleukin-1.beta. converting enzyme.

4-(4-cyano-2-thioaryl)-dihydropyrimidinones and using them

FIELD: medicine, pharmaceutics. SUBSTANCE: invention refers to new 4-(4-cyano-2-thioaryl)- dihydropyrimidin-2-one derivatives of formula (I), a method for preparing and using them. In formula , , both A and E mean C-R 7 , wherein R 7 mean hydrogen, Z means O, n means the number 0,1 or 2, R 1 means (C 1 -C 6 )-alkyl which may be substituted by the group hydroxy, (C 1 -C 4 )-alkoxy,(C 3 -C 6 )-cycloalkyl, phenyl or 5- or 6-member heteroaryl with two heteroatoms specified in nitrogen or sulphur, or may be substituted up to three times by fluorine, or means (C 3 -C 6 )-cycloalkyl or phenyl, R 2 means hydrogen, R 3 means cyano or a group of formulas -C(=O)-R 8 , -C(=O)-O-R 8 or -C(=O)-NH 2 , wherein R 8 means (C 1 -C 6 )-alkyl or (C 3 -C 6 )-alkenyl, R 4 means methyl or ethyl, or R 3 and R 4 are linked to each other and together form an annulated group of formula (II), R 9 means hydrogen, (C 1 -C 6 )-alkyl or (C 3 -C 6 )-cycloalkyl with (C 1 -C 6 )-alkyl may be substituted by a hydroxy group, aminocarbonylamino or (C 1 -C 4 )-acylamino, R 5 means hydrogen or (C 1 -C 6 )-alkyl. The other group and radical values are specified in the patent claim. EFFECT: compounds possess the properties of a neutrophil elastase (HNE) inhibitor and can find application in treating and/or preventing pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary emphysema, mediated by neutrophil elastase (HNE) activity. 16 cl, 4 tbl, 10 dwg, 202 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 497 813 (13) C2 (51) МПК C07D C07D A61K A61K A61P 239/22 401/04 31/506 31/505 11/00 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (24) Дата начала отсчета срока действия патента: 09.12.2008 Приоритет(ы): (30) Конвенционный приоритет: 20.12.2007 DE 102007061766.8 07.05.2008 DE 102008022521.5 17.10.2008 DE 102008052013.6 ( ...

Quinazoline derivatives, process for their preparation and their use as anti-cancer agents

본 발명은 B-Raf 억제 활성을 지니며, 따라서 항암 활성에 유용한 하기 화학식 I의 화합물 또는 이의 약학적으로 허용되는 염 및, 사람 또는 동물 신체의 치료 방법에 관한 것이다. 또한, 본 발명은 상기 화합물의 제조 방법, 이를 포함하는 약학적 조성물 및, 온혈 동물, 예컨대 사람에서의 항암 효과의 생성에 사용되는 약제의 제조에서의 이의 용도에 관한 것이다: 화학식 I 상기 화학식에서, 기 정의는 명세서에 정의된 바와 같다. B-Raf 억제 활성, 항암 활성, 퀴나졸린 유도체

Method for preparing phenacetylguanidines

Acrylic acid derivatives

FIELD: synthesis of organic compounds. SUBSTANCE: acrylic acid derivatives of the general formula: C 6 H 4 (A-W)C(CO 2 CH 3 )=CHOCH 3 wherein W is pyridyl substituted 1 to 4 times with substituents selected from halogen, C 1 -C 4 - alkyl optionally substituted with halogen; C 1 -C 4 -alkoxy, phenyl, phenoxy, amino, formamido, nitro, cyano, N-oxide; pyrimidinyl substituted 1 or 2 times with halogen; C 1 -C 4 - alkyl optionally substituted with halogen, C 1 -C 4 -alkoxy, phenyl, phenoxy optionally substituted with nitro or cyano; quinolinyl or quinolinyl haeide bonded with A by means of one of the ring carbon atoms; A is oxygen, S(O) n ; n is O, 1 or 2 provided that when W is S- trifluoromethylpyridin-2-yl; A is other than oxygen. EFFECT: improved properties of the title compounds. 9 tbl 7УОбЗ Ос ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВО ”” 2 039 044 ' (51) МПК 13) СЛ С 070 213/62, 215/227, 239/32, А 01 М 43/40, 43/42, 43154 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 5010295/04, 10.12.1991 (30) Приоритет: 17.04.1986 СВ 8609454; 8630825 (46) Дата публикации: 09.07.1995 (56) Ссылки: Патент США 4254262, кл. С 070213157, опублик. 1981. (71) Заявитель: Империал Кемикал Индастриз ПЛС (СВ) (72) Изобретатель: Вивьенн Маргарет Энтони[СВ], Джон Мартин Клаф[СВ], Пол Дефрейн[СВ], Кристофер Ричард Эйлз Годфри[СВ], Патрик Джелф Кроули[СВ], Ян Фергусон[ СВ], Майкл Гордон Хичингс[СВ] (73) Патентообладатель: Империал Кемикал Индастриз ПЛС (СВ) (54) ПРОИЗВОДНЫЕ АКРИЛОВОЙ КИСЛОТЫ (57) Реферат: Использование: синтез органических соединений, обладающих пестицидной активностью. Сущность — изобретения: производные акриловой кислоты общей ф-лы СвН4(А-МАС(СО2СНз)=СНОСНЗ, где М пиридил, замещенный 1 4 раза заместителями, выбранными из галогена, С 1-С4 -алкила, возможно замещенного галогеном, С1-Сл -алкокси, фенила, фенокси, амино, формамидо, нитро, циано, М-оксида; пиримидинил, замещенный 1 2 раза галогеном, С.-Сд -алкилпом, — возможно ...

Patent SU401047A3

Process for producing substituted ureas

1499180 Ureas and cyclic ureas AMIC SpA 8 Dec 1975 [10 Dec 1974] 50307/75 Heading C2C Ureas and cyclic ureas of the formula wherein n is 2, 3 or 4 and R and R<SP>1</SP> are hydrogen atoms or substituted or unsubstituted hydrocarbon radicals, are obtained by heating the corresponding carbamates of the formula M being an alkali metal or alkaline earth metal.

Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid derivatives as integrin antagonists

本发明涉及一类式Ⅰ表示的化合物及其药用盐、其药用组合物,以及用这些化合物和组合物作为α v β 3 拮抗剂的方法。