Chiral Diacylhydrazine Ligands for Modulating the Expression of Exogenous Genes via an Ecdysone Receptor Complex

The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements.

Crystalline Diacylhydrazine and the Use Thereof

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject.

PROCESS FOR THE PREPARATION OF CHIRAL HYDRAZIDES

The present invention relates to a process for the preparation of a chiral compound according to formula (V) wherein Ris preferably an alkyl residue preferably having from 1 to 6 carbon atoms, in particular to a process for the preparation of a chiral compound the crystalline chiral compounds as such, and their use for the preparation of an antifungal agent, in particular posaconazole. 2. The process of claim 1 , wherein in (1) claim 1 , the compound of formula (I) is provided by reacting propionaldehyde in a solvent with a compound of formula (i){'br': None, 'O═N—Y \u2003\u2003(i),'}{'smallcaps': 'D', 'preferably with nitrosobenzene, in the presence of a catalyst system, preferably comprising at least one organocatalyst, more preferably proline (Pro), more preferably -Pro, said catalyst system optionally further comprising a promoter, preferably an urea derivative, more preferably 1-(2-dimethylamino-ethyl)-3-phenyl urea.'}3. The process of claim 2 , wherein the reaction of propionaldehyde with the compound of formula (i) is carried out at a temperature in the range of from −15 to +5° C. claim 2 , preferably from −12 to +3° C. claim 2 , more preferably from −10 to 0° C. claim 2 , preferably in dichloromethane (DCM) as solvent.4. The process of claim 2 , wherein the reaction of propionaldehyde with the compound of formula (i) is carried out in the presence of a catalytical amount of an acid claim 2 , preferably acetic acid or propionic acid.5. The process of claim 1 , wherein in (2) claim 1 , the compound of formula (I) is reacted with HN—NH—CHO in the presence of a molecular sieve claim 1 , preferably having a pore diameter determined according to DIN 66131 in the range of from 0.3 to 0.5 nm (3 to 5 Angstrom).6. The process of claim 1 , wherein in (2) claim 1 , the compound of formula (I) is reacted with HN—NH—CHO at a temperature in the range of from −10 to +20° C. claim 1 , preferably from −5 to +5° C. claim 1 , preferably in dichloromethane (DCM) as solvent.7. ...

Processes for making hydrazides

A method is disclosed for preparing hydrazides from hydrazine and an acyl chloride which comprises the steps of (a) preparing a stirred substantially uniform slurry comprising hydrazine and an inert solvent at low temperature; and (b) adding an acyl chloride continuously to said slurry. The method avoids or limits production of undesired bis-hydrazide by-products. The method is used to prepare 3-methyl-3-mercaptobutanoic acid hydrazide, a molecule used to link calicheamicin to a monoclonal antibody.

"METHOD FOR PREPARING RAMALIN"

The present invention relates to a method for synthesizing ramalin, and more particularly to a method for synthesizing ramalin, which comprises allowing 2-hydrazinylphenol to react with L-glutamic acid having a protected carboxyl group at C-1 and a protected amino group at C-2, and a method for preventing decomposition of the ramalin. According to the present invention, ramalin having excellent antioxidant and anti-inflammatory activities can be synthesized in high yield, and thus can be produced in large amounts. In addition, ramalin can be stably maintained for a long period of time, and thus can be easily used for industrial purposes. 2. The method of claim 1 , wherein the 2-hydrazinylphenol is in tosylate form.3. The method of claim 2 , wherein the 2-hydrazinylphenol in tosylate form is prepared by a process comprising the steps of:(a) dissolving 2-aminophenol in methanol and adding hydrochloride gas thereto to obtain 2-aminophenol hydrochloride (HCl);(b) dissolving the 2-aminophenol hydrochloride in ethanol and adding isopentyl nitrite thereto to make a nitramide intermediate; and{'sub': '2', '(c) adding the intermediate to an ethanol solution containing para-toluenesulfonic acid (PTSA or TsOH) and tin chloride (SnCl), thereby obtaining 2-hydrazinylphenol tosylate.'}4. The method of claim 1 , wherein the L-glutamic acid containing a protected carboxyl group at C-1 and a protected amino group at C-2 is L-glutamic acid lactone wherein the carboxyl and amino groups are cyclized.5. The method of claim 4 , wherein the L-glutamic acid lacton is obtained by converting L-glutamic acid into a secondary amine form claim 4 , followed by cyclization.6. The method of claim 5 , wherein the secondary amine form is prepared by adding 2 claim 5 ,2 claim 5 ,2-trichloro-ethyl-chloroformate (Troc) to L-glutamic acid and allowing the mixture to react.7. The method of claim 1 , wherein the L-glutamic acid containing a protected carboxyl group at C-1 and a protected amino group at C- ...

Compound having hetero ring skeleton, and process for producing optically active compound using the aforementioned compound as asymmetric catalyst

The invention provides a compound having a heterocyclic skeleton of formula (I): wherein the substituents are as defined in the specification, as well as a tautomer thereof or a salt thereof. The invention also provides asymmetric synthesis methods involving the use of such a compound, tautomer thereof, or salt thereof, as a catalyst.

METHODS FOR RECOVERING AND ANALYZING AMINES

The objects of embodiments in the present disclosure are to provide a method capable of recovering two or more amine compounds at the same time from a gas or solution, and also to provide a method capable of analyzing the recovered amines. 1. A method for recovering an amine contained in a gas or in a solution , comprising:the step (A), in which said gas or solution is brought into contact with a solid adsorbent so that said solid adsorbent may retain the amine; andthe step (B), in which the amine retained by said solid adsorbent in the step (A) is eluted out by use of a basic compound-containing organic solvent;{'sub': '3', 'wherein said solid adsorbent has a substituent group represented by —SOM in which M is H or an alkali metal.'}2. The method according to for recovering an amine claim 1 , wherein said solid adsorbent has a substituent group represented by —R—SOMin whichM is H or an alkali metal, and{'sup': '2', 'sub': 2', 'r', '6', '4', 's', '2', 't', '6', '4', 'u', '2', 'v, '—R— is a substituent group represented by —(CH)—, —(CH)— or —(CH)—(CH)—(CH)—,'}provided that n, r, s, t, u and v are integers satisfying the conditions of: 5≦r≦24, 1≦s≦3, 0≦t≦24, 0≦u≦3, 0≦v≦24 and 2≦(t+u+v).3. The method according to for recovering an amine claim 1 , wherein said solid adsorbent has a substituent group represented by —(CH)—CH—SOH or —Si(CH)—CH—CH—SOH in which w is an integer satisfying the condition of 4≦w≦1000.4. The method according to for recovering an amine claim 1 , wherein said basic compound-containing organic solvent is methanol containing ammonia in an amount of 0.5 to 10 wt % inclusive.5. The method according to for recovering an amine claim 1 , wherein said basic compound-containing organic solvent further contains water or an aqueous solution containing an acid in an amount of 5 wt % or less.6. The method according for recovering an amine claim 1 , wherein said solid adsorbent is in the form of an ion-exchange column.7. The method according to for recovering an ...

METHOD FOR PREPARING DIPEPTIDYL PEPTIDASE-IV INHIBITOR AND INTERMEDIATE

The present invention relates to an improved method for preparing dipeptidyl peptidase-IV inhibitor and intermediate. The present invention is able to reduce preparation costs by using low cost reagents on reaction and is able to be used in mass production by improving yield. 2. The method as set forth in claim 1 , wherein the amine-protecting group is selected from the group consisting of butoxycarbonyl (Boc) claim 1 , benzyloxycarbonyl (Cbz) claim 1 , 9-fluorenylmethoxycarbonyl (Fmoc) claim 1 , acetyl claim 1 , benzoyl claim 1 , and tosyl. This application is a divisional of U.S. patent application Ser. No. 13/259,699, filed Sep. 23, 2011, which is 371 of PCT/KR2010/001947 filed on Mar. 30, 2010, which claims the benefit of Korean Patent Application No. 10-2009-0027105 filed Mar. 30, 2009, the contents of each of which are incorporated herein by reference.The present invention relates to an improved method for manufacturing dipeptidyl peptidase-IV inhibitor and an intermediate.DPP-IV is an enzyme functioned as a cleavage of N-terminal dipeptide of peptide having a terminal sequence of H-Xaa-Pro-Y (or H-Xaa-Ala-Y, where Xaa is any lipophilic amino acid, Pro is proline, and Ala is alanine) (Heins J et al. 1988; 161), and also called DP-IV, DP-4, or DAP-IV. After finding out that DPP-IV degrades glucagon-like protein-1 (hereinafter, called as to GLP-1) that is known to have a powerful effect on a control function of insulin to blood glucose contents after dinner (Mentlein R et al. 1993:829-35), a possibility as very powerful therapeutic agent for Type II diabetes is presented, and then a study for developing DPP-IV inhibitor has become faster.Merck Company developed triazolo piperazine compound with beta-amino acid structure, sitagliptin, during an investigation about DPP-IV inhibitor. The compound is the first DPP-IV inhibitor for treating Type II diabetes and has now become commercially available under a trademark, Januvia™, around the world after obtaining the new ...

METHOD FOR THE PREPARATION OF DIAZOALKANES

The present invention relates to a method of forming diazoalkanes. One aspect of the present invention provides a method for the production of a N-alkyl-N-nitroso compound from a starting material, comprising the use of a tribasic acid to acidify an amine. A second aspect of the present invention provides a method for the production of a diazoalkane, comprising reacting a N-alkyl-N-nitroso compound with a base and a phase transfer catalyst, wherein no organic solvent is used. 1. A method for the production of a diazoalkane , comprising reacting a N-alkyl-N-nitroso compound with a base and a phase transfer catalyst , wherein no organic solvent is used.2. The method according to wherein the phase transfer catalyst is tetrabutyl ammonium bromide (TBAB).3. The method according to wherein the TBAB is used at a loading of between 0.1 mol % and 2 mol %.4. The method according to wherein the TBAB is used at a loading of 1 mol %.5. The method according to any one of to wherein the reaction occurs at a temperature of between 0° C. and 40° C.6. The method according to wherein the reaction occurs at a temperature of less than 10° C.7. The method according to wherein the reaction occurs at a temperature of 10° C.8. The method according to any one of to wherein the base is present at a concentration of between 10% and 50% w/w.9. The method according to wherein the base is present at a concentration of 50% w/w.10. The method according to any one of to wherein the yield of the diazoalkane is above 75%.11. The method according to wherein the yield of the diazoalkane is approximately 90%.12. The method according to any one of to wherein the diazoalkane is diazomethane.13. The method according to any one of to wherein the N-alkyl-N-nitroso compound is a N-methyl-N-nitroso compound.15. The method according to wherein Ris Rand the organic by-product of the diazoalkane production separates from the reaction mixture as a discrete phase.16. The method according to wherein Ris Rand the ...

METHOD FOR SYNTHESIZING RAMALIN AND RAMALIN PRECURSOR BY USING GLUTAMIC ACID DERIVATIVE AND HYDROXY ANILINE OR HYDROXY ANILINE HAVING PROTECTED HYDROXY GROUP

Disclosed is a method of the synthesis of ramalin. It comprises reacting a glutamic acid derivative, which is prepared using alkylchloroformate, with a hydrazine salt compound, which is prepared from hydroxy aniline, whether protected or not. The synthesis method allows ramalin, excellent in antioxidant and anti-inflammatory activity, to be simply synthesized at stable yield even without use of a highly toxic solvent such as DMF. In addition, the method is cost competitive, and provides ramalin at high efficiency, thus enabling the mass production of ramalin. 3. The method of claim 2 , wherein the glutamic acid derivative represented by Chemical Formula 5 is prepared by protecting an amino acid group of the glutamic acid with a carbobenzyloxy group claim 2 , and esterifying an alpha carboxyl group with a benzyl group.4. The method of claim 1 , wherein the hydrazine salt compound represented by Chemical Formula 3 is prepared by reducing azo compound from 2-hydroxy aniline or an acid salt of protected hydroxy aniline5. The method of claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , pentyl claim 1 , hexyl claim 1 , heptyl claim 1 , octyl claim 1 , 2-ethylhexyl claim 1 , substituted alkyl claim 1 , and cycloalkyl.6. The method of claim 1 , wherein Ris ethyl.7. The method of claim 1 , wherein Ris hydrogen.8. The method of claim 1 , wherein Ris a benzyl group for protecting hydroxy.9. The method of claim 1 , wherein the acid is hydrochloric acid claim 1 , bromic acid claim 1 , iodic acid claim 1 , or P-toluenesulfonic acid. The present invention relates to a method of the synthesis of ramalin. More particularly, the present invention relates to a method of synthesizing ramalin by reacting a glutamic acid derivative which is prepared using alkylchloroformate, with hydroxy aniline, or protected hydroxy aniline.A lichen, resembling a non-flowering plant, is a ...

Bioavailable Diacylhydrazine Ligands for Modulating the Expression of Exogenous Genes via an Ecdysone Receptor Complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene. 16-. (canceled)9. The method of claim 8 , wherein the ecdysone receptor complex is a chimeric ecdysone receptor complex and the DNA construct further comprises a promoter.10. The method of claim 8 , wherein the subject is a plant.11. The method of claim 8 , wherein the subject is a mammal. This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to non-steroidal ligands for natural and mutated nuclear receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene within a host cell using these ligands and inducible gene expression system.Various publications are cited herein, the disclosures of which are incorporated by reference in their entireties. However, the citation of any reference herein should not be construed as an admission that such reference is available as “Prior Art” to the instant application.In the field of genetic engineering, precise control of gene expression is a valuable tool for studying, manipulating, and controlling development and other physiological processes. Gene expression is a complex biological process involving a number of specific protein-protein interactions. In order for gene expression to be triggered, such that it produces the ...

Crystalline Diacylhydrazine and the Use Thereof

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject.

COMPOSITION, METHOD AND USE

A quaternary ammonium salt of formula (I): wherein X is a linking group; Y is O, NH or NRwherein Ris H or an optionally substituted hydrocarbyl group; Q is a moiety that includes a quaternary ammonium cation; A is an anion; Ris an optionally substituted alkylene group; Ris hydrogen or an optionally substituted hydrocarbyl group; and n is 0 or a positive integer; provided that n is not 0 when Ris hydrogen. 3. (canceled)5. The salt according to wherein the quaternary ammonium salt additive is prepared by reacting:(a) a hydrocarbyl substituted dicarboxylic acid or anhydride thereof; with{'sup': 3', '2, 'sub': 'n', '(b) an alcohol of formula R(OR)OH;'}(c) a reactive alcohol or amine including a tertiary amino group; and(d) a quaternising agent.6. The salt according to wherein X is an optionally substituted alkylene or arylene group and Ris an optionally substituted hydrocarbyl group.7. The salt according to wherein n is 0 and Ris an optionally substituted alkyl or alkenyl group having 4 to 40 carbon atoms.8. The salt according to wherein each Ris ethylene or propylene.9. The salt according to wherein Ris hydrogen and n is at least 1.10. The salt according to wherein Ris an optionally substituted alkyl group having 4 to 40 carbon atoms and n is from 1 to 40.12. The salt according to wherein Ris an optionally substituted alkylene group having 1 to 6 carbon atoms claim 11 , Ris Cto Calkyl claim 11 , Ris Cto Calkyl and Ris an unsubstituted Cto Calkyl group or a hydroxy substituted Cto Calkyl group.13. The salt according to wherein Ais a carboxylate anion.14. The salt according to wherein the quaternary ammonium salt additive is prepared by reacting:(a) an optionally substituted succinic acid or anhydride thereof;{'sup': 2', '3, 'sub': 'n', '(b) an alcohol of formula H(OR)OH or ROH;'}(c) a reactive alcohol including a tertiary amino group; and(d) a quaternising agent.15. The salt according to wherein the quaternary ammonium salt additive is prepared by reacting:{'sub': 20', ...

PROCESSES FOR PREPARING TUBULYSIN DERIVATIVES AND CONJUGATES THEREOF

The invention described herein pertains to processes for preparing tubulysin derivatives, conjugates of tubulysins, and intermediates therefore. In one illustrative embodiment of the invention, processes for derivatives or analogs of natural tubulysins including compounds of formula (T). In another embodiment, vitamin receptor binding conjugates of tubulysins are described. The processes include one or more steps described herein. In another embodiment, a process is described for preparing a compound of formula B, wherein R5 and R6 are as described in the various embodiments herein, such as each being independently selected from optionally substituted alkyl or optionally substituted cycloalkyl; and R8 is C1-C6 n-alkyl; wherein the process comprises the step of treating a compound of formula A with a silylating agent, such as triethylsilyl chloride, and a base, such as imidazole in an aprotic solvent. 811-. (canceled)12. The process of wherein Y is RC(O)O claim 1 , where Ris selected from the group consisting of optionally substituted alkyl and optionally substituted cycloalkyl.13. (canceled)14. The process of wherein Ris n-butyl.15. (canceled)16. The process of wherein Ris methyl.17. (canceled)18. (canceled)19. The process of wherein Aris 4-hydroxyphenyl.20. (canceled)21. The process of wherein Ris methyl.22. (canceled)23. The process of wherein Ris iso-propyl.2426-. (canceled)27. The process of wherein Ris methyl.2830-. (canceled)31. The process of wherein Aris 3-nitro-2-pyridyl.3236-. (canceled)37. The process of wherein L is —(CR)CRR—.38. The process of wherein p is 1.3941-. (canceled)4346-. (canceled)47. The compound of wherein Aris 3-nitro-2-pyridyl.48. The compound of wherein Aris 4-substituted phenyl. The present application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 61/617,386, filed Mar. 29, 2012, U.S. Provisional Application No. 61/684,450, filed Aug. 17, 2012, U.S. Provisional Application No. 61/771,451, filed Mar. 1, ...

Rhodium catalyst and method for producing amine compound

[Problem] Provision of a superior rhodium catalyst and a production method of amine compound. [Solving Means] A rhodium complex coordinated with a compound represented by the formula

NOVEL CURING AGENTS AND DEGRADEABLE POLYMERS AND COMPOSITES BASED THEREON

The present invention provides, among others, compounds of Formula (I) or a salt thereof, methods for making these compounds, degradable polymers and reinforced composites made therefrom, and methods for degrading and/or recycling the degradable polymers and reinforced composites. 2. The compound of claim 1 , wherein both m and n are 0.3. The compound of claim 1 , wherein both m and n are 1.4. The compound of claim 1 , wherein each of A and B claim 1 , independently claim 1 , is alkylene claim 1 , alkenylene claim 1 , arylene claim 1 , alkylene-arylene claim 1 , alkenylene-arylene claim 1 , alkynylene-arylene claim 1 , heteroarylene claim 1 , alkylene-heteroarylene claim 1 , alkenylene-heteroarylene claim 1 , or alkynylene-heteroarylene.5. The compound of claim 1 , wherein each of A and B claim 1 , independently claim 1 , is alkylene or arylene.6. The compound of claim 5 , wherein both A and B are claim 5 , at the same time claim 5 , alkylene or arylene.7. The compound of claim 6 , wherein both A and B are claim 6 , at the same time claim 6 , methylene claim 6 , ethylene claim 6 , or phenylene.8. The compound of claim 1 , wherein each of Rand R claim 1 , independently claim 1 , is hydrogen claim 1 , alkyl claim 1 , cycloalkyl claim 1 , heterocyclic claim 1 , heterocycloalkyl claim 1 , alkenyl claim 1 , cycloalkenyl claim 1 , aryl claim 1 , heteroaryl claim 1 , alkyl-hetero-alkyl claim 1 , alkynyl claim 1 , alkylene claim 1 , alkylene-hetero-alkylene claim 1 , alkenylene claim 1 , alkylene-hetero-alkenylene claim 1 , alkynylene claim 1 , or alkylene-hetero-alkynylene; or Rand R claim 1 , together with the carbon atom to which they are attached claim 1 , form a 3- to 7-membered saturated or unsaturated ring.9. The compound of claim 8 , wherein each of Rand R claim 8 , independently claim 8 , is hydrogen or alkyl claim 8 , or Rand R claim 8 , together with the carbon atom to which they are attached claim 8 , form a 3- to 7-membered saturated ring.10. The compound of ...

CRYSTALLINE DIACYLHYDRAZINE AND THE USE THEREOF

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject. 119-. (canceled)20. A method of regulating gene expression of a gene of interest in a host cell , the method comprising contacting said host cell with a composition comprising crystalline (R)-3.5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide Form III Form IV , Form V , Form VI Form VII , Form VIII , or Form IX , wherein:Form III is characterized as having a powder x-ray diffraction pattern with peaks at 8.14, 8.52, 17.00, 18.56, and 22.19 degrees 2Θ;Form IV is characterized as having a powder x-ray diffraction pattern with peaks at 6.83, 10.31, 11.30, 12.18, 12.98, 13.69, 15.11, 16.23, 17.60, 17.99, 20.70, 21.15, 21.68, 22.71, 23.79, and 24.86 degrees 2Θ;Form V is characterized as having a powder x-ray diffraction pattern with peaks at 9.38, 12.22, 13.18, 14.98, 17.32, 18.40, 22.41, 23.40, 23.55, 24.63, 24.79, 25.61, 28.02, and 31.77 degrees 2Θ;Form VI is characterized as having a powder x-ray diffraction pattern with peaks at 9.38, 12.23, 13.25, 17.48, 18.41, and 22.41 degrees 2Θ;Form VII is characterized as having a powder x-ray diffraction pattern with peaks at 8.18, 9.71, 13.30, 16.22, 17.73, 20.98, 21.20, 22.76, 24.68, 26.72, and 29.39 degrees 2Θ;Form VIII is characterized as having a powder x-ray diffraction pattern with peaks at 10.05, 10.77, 14 ...

Chiral Diacylhydrazine Ligands for Modulating the Expression of Exogenous Genes via an Ecdysone Receptor Complex

The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements. 125-. (canceled)27. The process of wherein B is 3 claim 26 ,5-di-methylphenyl.28. The process of wherein A is 2-ethyl-3-methoxyphenyl.29. The process of wherein Ris tert-butyl.32. The method of claim 31 , wherein said ecdysone receptor complex is a chimeric ecdysone receptor complex and said DNA binding sequence further comprises a promoter.33. The method of wherein the subject is a plant.34. The method of wherein the subject is an animal.35. The method of wherein the subject is a mammal.36. The method of wherein the subject is a human.37. The method of claim 31 , wherein said cells are autologous cells.38. The method of claim 37 , wherein said autologous cells contain said ecdysone receptor complex and the DNA binding sequence for the ecdysone complex claim 37 , and said cells are implanted into said subject to make it transgenic.39. The method of claim 38 , wherein said implanted is by injection.40. The method of claim 39 , wherein said injection is into a tumor.41. The method of claim 31 , wherein said ligand is administered to said transgenic subject as part of a pharmaceutical composition comprising a pharmaceutically acceptable carrier.42. The method of claim 41 , wherein said pharmaceutical composition is administered orally.43. The method of claim 41 , wherein said pharmaceutically acceptable carrier comprises a lipophilic solvent.47. The ...

PROCESSES FOR MAKING HYDRAZIDES

A method is disclosed for preparing hydrazides from hydrazine and an acyl chloride which comprises the steps of (a) preparing a stirred substantially uniform slurry comprising hydrazine and an inert solvent at low temperature; and (b) adding an acyl chloride continuously to said slurry. The method avoids or limits production of undesired bis-hydrazide by-products. The method is used to prepare 3-methyl-3-mercaptobutanoic acid hydrazide, a molecule used to link calicheamicin to a monoclonal antibody. 133-. (canceled)34. A method of preparing a hydrazide from hydrazine and an acyl halide comprising the steps of:(a) preparing a slurry comprising hydrazine and an inert solvent; and(b) adding an acyl halide continuously to said slurry, wherein the acyl halide further comprises a protected thiol.35. The method according to wherein the acyl halide is added substantially drop wise to the slurry.36. The method according to wherein the acyl halide comprises a benzyl thioether.38. The method according to wherein L is —CH—.39. The method according to wherein Rand Rare each independently methyl.40. The method according to wherein P is a benzyl group claim 37 , optionally substituted on the phenyl ring.41. The method according to wherein P is p-methoxybenzyl group.43. The method according to wherein the inert solvent is methylene chloride.45. The method according to wherein L is —CH—.46. The method according to wherein Rand Rare each independently methyl.47. The method according to wherein P is a benzyl group claim 44 , optionally substituted on the phenyl ring.48. The method according to wherein P is p-methoxybenzyl group.52. The method according to wherein L is —CH—.53. The method according to wherein Rand Rare each independently methyl.54. The method according to wherein P is a benzyl group claim 51 , optionally substituted on the phenyl ring.55. The method according to wherein P is p-methoxybenzyl group.57. The method according to wherein the continuous addition of acid ...

Crystalline Diacylhydrazine and the Use Thereof

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject. 1. Crystalline (R)-3 ,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide or crystalline (S)-3 ,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide Form V , Form VI , Form VII , Form VIII , or Form IX , wherein:Form V is characterized as having a powder x-ray diffraction pattern with peaks at 9.38, 12.22, 13.18, 14.98, 17.32, 18.40, 22.41, 23.40, 23.55, 24.63, 24.79, 25.61, 28.02, and 31.77 degrees 2Θ;Form VI is characterized as having a powder x-ray diffraction pattern with peaks at 9.38, 12.23, 13.25, 17.48, 18.41, and 22.41 degrees 2Θ;Form VII is characterized as having a powder x-ray diffraction pattern with peaks at 8.18, 9.71, 13.30, 16.22, 17.73, 20.98, 21.20, 22.76, 24.68, 26.72, and 29.39 degrees 2Θ;Form VIII is characterized as having a powder x-ray diffraction pattern with peaks at 10.05, 10.77, 14.06, 16.76, 18.11, 18.32, 18.43, 20.89, 21.71, 21.87, 24.07, 24.90, and 28.71 degrees 2Θ; andForm IX is characterized as having a powder x-ray diffraction pattern with peaks at 7.06, 15.74, and 18.71 degrees 2Θ.211-. (canceled)12. The crystalline (R)-3 claim 1 ,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide form of having an average particle size distribution of about 10 μm or ...

(R)-Nifuratel, its use for the treatment of infections and synthesis of (R) and (S)-Nifuratel

(R)-Nifuratel is disclosed together with its use as bactericide and bacteriostatic agent as well as the pharmaceutical compositions containing the same; (R)-nifuratel has been surprisingly found to possess a better antimicrobial profile than either nifuratel racemate or (S)-nifuratel. A new procedure for the synthesis of both (R)-Nifuratel and (S)-Nifuratel is also disclosed. 122-. (canceled)23. (R)-Nifuratel.24. A method of treating a condition selected from external genital infections claim 23 , vaginal infections claim 23 , urinary infections claim 23 , gastrointestinal infections or respiratory infections in a subject in need thereof claim 23 , comprising administration of an effective amount of (R)-Nifuratel according to .25. The method according to claim 24 , wherein the infection is due either to bacteria or to protozoa.26. The method according to claim 24 , wherein the subject is a mammal claim 24 , including a human.27. The method according to claim 26 , wherein the (R)-Nifuratel is administered at dosage regimen comprised between 0.001 and 1000 mg/Kg/day.28. A pharmaceutical formulation comprising (R)-Nifuratel according to and at least a pharmaceutically acceptable excipient or adjuvant.30. The process according to claim 29 , wherein step (a) is performed between 30 and 100° C.31. The process according to claim 30 , wherein step (a) is performed at about 90° C.32. The process according to claim 29 , wherein step (a) is performed in a polar solvent or under neat conditions.33. The process according to claim 32 , wherein step (a) is performed in water.34. The process according to claim 29 , wherein step (b) is performed by reacting compound 1 with a C-C-dialkyl carbonate in presence of a catalytic amount of an alkaline or alkaline-earth metal C-Calkoxide claim 29 , followed by protection of the free amino group as a carbamate.35. The process according to claim 34 , wherein the C-C-dialkyl carbonate is diethyl carbonate.36. The process according to claim 34 ...

Methods and systems for neutralization of hydrazine

Methods of and systems for remediating hydrazine spills, solutions, and hydrazine-contaminated objects including areas thereof comprise reacting 1,1-Dimethylhydrazine with α-ketoacids and adding a reducing agent to the reaction of 1,1-Dimethylhydrazine with said α-ketoacids.

Process for the preparation of 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1h-1,2,4-triazol-3-yl)phenyl)amino)-n-(methyl-d3)pyridazine-3-carboxamide

The invention relates to an improved process for synthesizing 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide of the formula: [INSERT CHEMICAL STRUCTURE HERE] Compound I is currently in clinical trials for the treatment of auto-immune and auto-inflammatory diseases such as psoriasis.

PHARMACEUTICALLY ACCEPTABLE SALTS OF FATTY ACIDS

The present disclosure provides pharmaceutically acceptable stable salt forms of 15-lipoxygenase products, such as 15-HETrE lysine salt, compositions comprising same and methods of making and using same. 1. A salt of a 15-lipoxygenase product.2. The salt of claim 1 , wherein the salt is a pharmaceutically acceptable salt.3. The salt of claim 1 , wherein the salt comprises a lysine salt of the 15-lipoxygenase product.4. The salt of claim 1 , wherein the salt comprises a sodium salt of the 15-lipoxygenase product.5. The salt of claim 1 , wherein the salt comprises an ornithine salt of the 15-lipoxygenase product.6. The salt of claim 1 , wherein the salt comprises a piperazine salt of the 15-lipoxygenase product.7. The salt of claim 1 , wherein the salt comprises a meglumine salt of the 15-lipoxygenase product.8. The salt of further comprising the 15-lipoxygenase product in free acid form.9. The salt of claim 1 , wherein the salt is selected from the group consisting of: sodium claim 1 , lysine claim 1 , ornithine claim 1 , piperazine claim 1 , meglumine claim 1 , and combinations thereof.10. The salt of claim 1 , wherein the 15-lipoxygenase product is selected from the group consisting of: 13-HODE claim 1 , 15-HETrE claim 1 , 15-OHEPA claim 1 , 15-HETE claim 1 , and combinations thereof.11. 15-Hydroxy-5 claim 1 , 8 claim 1 ,11 claim 1 ,13-eicosatetraenoic acid lysine salt.12. A pharmaceutical composition comprising a salt form of a 15-lipoxygenase product.13. The pharmaceutical composition of further comprising an excipient.14. The pharmaceutical composition of claim 12 , wherein after storage for at least about 4 weeks claim 12 , the pharmaceutical composition comprises at least about 98% claim 12 , at least about 99% claim 12 , or about 100% of an initial amount of the salt form of the 15-lipoxygenase product.15. The pharmaceutical composition of claim 12 , wherein after storage for at least about 10 weeks or at least 24 weeks claim 12 , the pharmaceutical ...

(R)-Nifuratel, its use for the treatment of infections and synthesis of (R) and (S)-Nifuratel

(R)-Nifuratel is disclosed together with its use as bactericide and bacteriostatic agent as well as the pharmaceutical compositions containing the same; (R)-nifuratel has been surprisingly found to possess a better antimicrobial profile than either nifuratel racemate or (S)-nifuratel. A new procedure for the synthesis of both (R)-Nifuratel and (S)-Nifuratel is also disclosed. 2. The process according to claim 1 , wherein step (a) is performed between 30 and 100° C.3. The process according to claim 2 , wherein step (a) is performed at about 90° C.4. The process according to claim 1 , wherein step (a) is performed in a polar solvent or under neat conditions.5. The process according to claim 4 , wherein step (a) is performed in water.6. The process according to claim 1 , wherein step (b) is performed by reacting compound 1 with a C-C-dialkyl carbonate in presence of a catalytic amount of an alkaline or alkaline-earth metal C-Calkoxide claim 1 , followed by protection of the free amino group as a carbamate.7. The process according to claim 6 , wherein the C-C-dialkyl carbonate is diethyl carbonate.8. The process according to claim 6 , wherein the alkaline or alkaline-earth metal C-Calkoxide is sodium methoxide or sodium ethoxide.9. The process according to claim 6 , wherein the free amino group is protected as a tert-butyl-carbamate.10. The process according to claim 7 , wherein the reaction of compound 1 with diethyl carbonate is performed under neat conditions or in a polar organic solvent.11. The process according to claim 10 , wherein the polar organic solvent is methanol claim 10 , THF or DMF.12. The process according to claim 6 , wherein protection of the free amino group is achieved by reaction with a C-Calkyl chloroformate or a C-Calkyl carbonate.13. The process according to claim 12 , wherein protection of the free amino group is achieved by reaction with methyl-chloroformate claim 12 , ethyl-chloroformate or di-tert-butyl dicarbonate.14. The process according ...

Process for Making 2,5-Dihalogenated Phenol

The present invention relates to a process for reacting chemical compounds comprising the step of reacting a compound of formula (IV) wherein Hal is independently selected from CI or Br, and X″ is a monovalent anion, in the presence of an inorganic acid, wherein the aqueous inorganic acid has a concentration of at least about 60%, at a temperature of about 140° C. to Cabout 250° C., to obtain a compound of formula (V) wherein Hal is as defined above. 117-. (canceled)19. The process of claim 18 , wherein product of formula (V) is continuously removed from the reaction system using steam distillation.20. The process of claim 18 , wherein X is HSO claim 18 , and the inorganic acid is HSO claim 18 , and wherein the concentration of the HSOis at least about 65%.21. The process of claim 20 , wherein at least part of the HSOis recycled.22. The process of claim 18 , wherein the reaction is carried out at a temperature of at least about 160° C.24. The process of claim 23 , wherein the step of diazotating the compound of formula (III) to obtain the compound of formula (IV) is carried out in HSOhaving a concentration of at least about 40% in the presence of NOHSO.25. The process of claim 24 , wherein NOSOis obtained by feeding NOgas to sulfuric acid having a concentration of at least about 60% claim 24 , and wherein the NOgas is a mixture of NO and NOin a molar ratio of about 1:1.26. The process of claim 18 , wherein the water used for steam distillation is recycled in a closed water loop.30. The process of claim 29 , wherein the step of reacting the compound of formula (V) to obtain a compound of formula (VI) is carried out in the presence of an alkali metal hydroxide and carbon dioxide.33. The process of claim 18 , wherein(a) Hal is Cl; and/or{'sup': '1', '(b) Ris selected from sodium and potassium; and/or'}{'sup': 1′', '1′, '(c) R is selected from sodium and potassium, or R is selected from ethyl and methyl; and/or'}{'sup': '2', '(d) Ris selected from ethyl and methyl.'} ...

SYNTHETIC METHODS AND COMPOUNDS RELATED THERETO

Disclosed herein are synthetic methods and compounds related to the compounds that are useful as or in the production of biologically active compounds. Stereoselective and stereospecific synthetic methods are disclosed to produce compounds, such as, for example, γ,δ-unsaturated-β-hydroxyesters and aminated derivatives thereof, at high yields with desired stereochemistry. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The synthetic method of claim 1 , wherein Ris hydrogen and Ris selected from aryl claim 1 , cycloalkyl claim 1 , cycloalkenyl claim 1 , heterocyclyl claim 1 , heteroaryl claim 1 , -alkyl-aryl claim 1 , -alkenyl-aryl claim 1 , alkynyl-aryl claim 1 , -alkyl-cycloalkyl claim 1 , -alkenyl-cycloalkyl claim 1 , alkynyl-cycloalkyl claim 1 , alkyl-heterocyclyl claim 1 , -alkenyl-heterocyclyl claim 1 , alkynyl-heterocyclyl claim 1 , -alkyl-heteroaryl claim 1 , -alkenyl-heteroaryl claim 1 , alkynyl-heteroaryl claim 1 , alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , and haloalkyl.3. The synthetic method of claim 1 , wherein Ris hydrogen.4. The synthetic method of claim 1 , wherein Ris selected from alkyl claim 1 , alkenyl claim 1 , and alkynyl.5. The synthetic method of claim 1 , wherein the ketoreductase is selected from 130 claim 1 , NADH-101 claim 1 , P3-G09 claim 1 , and P3-H12.9. The synthetic method of claim 8 , wherein the ester of the third compound is reduced to form an alcohol in a fourth compound.11. The synthetic method of claim 10 , wherein the method further comprises cleaving the N—N bond in the fifth compound claim 10 , thereby forming a sixth compound.15. The synthetic method of claim 13 , wherein the ester of the third compound is reduced to form an alcohol in a fourth compound.18. The synthetic method of claim 17 , wherein the method further comprises cleaving the N—N bond in the fifth compound claim 17 , thereby forming a sixth ...

PROCESS FOR THE CYCLOPROPANATION OF OLEFINS USING N-METHYL-N-NITROSO COMPOUNDS

A process of converting a carbon-carbon double bond on a substrate into a cyclopropane ring, which method comprises the step of treating the substrate with a N-alkyl-N-nitroso compound, a transition metal catalyst and an aqueous base, wherein the N-alkyl-N-nitroso compound is formed by reacting an alkyl amine with an alkali metal nitrite in the presence of a mono-basic or di-basic acid, or a mixture thereof, and wherein the N-alkyl-N-nitroso compound is not distilled before it is mixed with the substrate, catalyst and base. 1. A process of converting a carbon-carbon double bond on a substrate into a cyclopropane ring , the process comprising treating the substrate with a N-alkyl-N-nitroso compound , a transition metal catalyst and an aqueous base , wherein the N-alkyl-N-nitroso compound is formed by reacting an alkyl amine with an alkali metal nitrite in the presence of a mono-basic or di-basic acid comprising a mono-basic or di-basic carboxylic acid , or a mixture thereof , and wherein the N-alkyl-N-nitroso compound is not distilled before it is mixed with the substrate , catalyst and base.2. The process of claim 1 , wherein the acid is formic acid or acetic acid.3. The process according to claim 1 , wherein the acid is a mixture of a mono-basic or di-basic carboxylic acid and an organic or inorganic acid having a lower pKa than said carboxylic acid.415. The process according to claim claim 1 , wherein the acid is a mixture of acetic acid and sulphuric acid.5. The process according to claim 1 , wherein the N-alkyl-N-nitroso compound is (N-methyl-N-nitroso)-4-amino-4-methyl-2-pentanone.7. The process according to claim 6 , wherein the substrate is an isoprenoid.10. The process according to claim 7 , wherein the isoprenoid is alpha farnesene or beta farnesene.11. The method according to claim 1 , wherein the catalyst is a palladium catalyst. The present application is a continuation of U.S. Ser. No. 15/758,795 filed on Mar. 9, 2018, which is a national stage ...

PREPARATION OF HALOALKOXYARYLHYDRAZINES AND INTERMEDIATES THEREFROM

This document is related to the field of preparation of haloalkoxyarylhydrazines and certain intermediates derived therefrom, where said intermediates are useful in the preparation of certain pesticides disclosed in U.S. Pat. No. 8,178,658. 3. A process according to wherein (1 a) R is trifluoromethoxy or pentafluoroethoxy.4. A process according to wherein (1a) X is Br.5. A process according to wherein (1a) Rand Rare phenyl.6. A process according to wherein (1a) palladium catalyst complex is tetrakis(triphenyl-phosphine)palladium(0) claim 1 , tris(dibenzylideneacetone)dipalladium(0) (Pd(dba)) claim 1 , or is prepared in situ by contacting palladium (II) acetate (Pd(OAc)); palladium (II) chloride (PdCl) claim 1 , sodium tetrachloropalladate (NaPdCl); bis(dibenzylideneacetone) palladium(II) (Pd(dba)) claim 1 , with a ligand claim 1 , selected from triphenylphosphine (PPh) claim 1 , 1 claim 1 ,1′-bis(diphenylphosphino)ferrocene (dppf) claim 1 , dibenzylideneacetone (dba); 2′-bis(diphenylphosphino)-1 claim 1 ,1′-binaphthyl (BINAP); or 2-dicyclohexylphosphino-2′-methylbiphenyl (MePhos).7. A process according to wherein (1a) a molar ratio of the haloalkoxyarylhalide of Formula 1 and a hydrazone of Formula 1.1 is from about 1.5:1 to about 1:1.5.8. A process according to wherein (1a) the reaction of the haloalkoxyarylhalide of Formula 1 with the hydrazine of Formula 1.1 is conducted in the presence of sodium tert-butoxide (NaOBu) claim 1 , potassium tert-butoxide (KOBu) claim 1 , lithium hexamethyldisilazide (LiHMDS) claim 1 , sodium carbonate (NaCO) claim 1 , potassium carbonate (KCO) claim 1 , cesium carbonate (CsCO) claim 1 , tripotassium phosphate (KPO) claim 1 , or mixtures thereof.9. A process according to wherein (1a) the pH is from about 12 to about 14.10. A process according to wherein (1a) the temperature from about 95-100° C.11. A process according to wherein (1b) is conducted in methanol or ethanol.12. A process according to wherein (1b) the pH is from about −1 ...

PREPARATION OF HALOALKOXYARYLHYDRAZINES AND INTERMEDIATES THEREFROM

The invention in this document is related to the field of preparation of haloalkoxyarylhydrazines and certain intermediates derived therefrom, where said intermediates are useful in the preparation of certain pesticides disclosed in U.S. Pat. No. 8,178,658. 3. A process according to wherein R is trifluoromethoxy or pentafluoroethoxy.4. A process according to wherein (1a) a 1:1 molar ratio of the haloalkoxyaniline and sodium nitrite is used.5. A process according to wherein (1a) the reaction is conducted in water claim 1 , formic acid claim 1 , n-butanol claim 1 , isopropanol claim 1 , nitromethane claim 1 , ethanol claim 1 , methanol claim 1 , acetic acid claim 1 , or mixtures thereof.6. A process according to wherein (1a) the reaction is conducted in the presence of hydrochloric acid claim 1 , nitric acid claim 1 , phosphoric acid claim 1 , sulphuric acid claim 1 , boric acid claim 1 , hydrofluoric acid claim 1 , hydrobromic acid claim 1 , perchloric acid claim 1 , tetrafluoroboric acid claim 1 , or mixtures thereof.7. A process according to wherein (1a) the pH of the reaction is from about −1 to about 1.8. A process according to wherein (1a) the reaction is conducted at a temperature from about −5 to about 5° C.9. A process according to wherein (1b) is conducted in water claim 1 , formic acid claim 1 , n-butanol claim 1 , isopropanol claim 1 , nitromethane claim 1 , ethanol claim 1 , methanol claim 1 , acetic acid claim 1 , or mixtures thereof.10. A process according to wherein (1b) the reaction is conducted in the presence of a reducing agent claim 1 , said reducing agent is sodium dithionite claim 1 , tin chloride claim 1 , hydrogen claim 1 , or ammonium formate.11. A process according to wherein (1b) the pH of the reduction reaction mixture is from about 9 to about 12.12. A process according to wherein (1b) the reaction is conducted at a temperature from about −5 to about 5° C.13. A process according to wherein (2a) is conducted in pyridine claim 2 , lutidine ...

PHARMACEUTICALLY ACCEPTABLE SALTS OF FATTY ACIDS

The present disclosure provides pharmaceutically acceptable stable salt forms of 15-lipoxygenase products, such as 15-HETrE lysine salt, compositions comprising same and methods of making and using same. 1. A salt of a 15-lipoxygenase product.2. The salt of claim 1 , wherein the salt is a pharmaceutically acceptable salt.3. The salt of claim 1 , wherein the salt comprises a lysine salt of the 15-lipoxygenase product.4. The salt of claim 1 , wherein the salt comprises a sodium salt of the 15-lipoxygenase product.5. The salt of claim 1 , wherein the salt comprises an ornithine salt of the 15-lipoxygenase product.6. The salt of claim 1 , wherein the salt comprises a piperazine salt of the 15-lipoxygenase product.7. The salt of claim 1 , wherein the salt comprises a meglumine salt of the 15-lipoxygenase product.8. The salt of further comprising the 15-lipoxygenase product in free acid form.9. The salt of claim 1 , wherein the salt is selected from the group consisting of: sodium claim 1 , lysine claim 1 , ornithine claim 1 , piperazine claim 1 , meglumine claim 1 , and combinations thereof.10. The salt of claim 1 , wherein the 15-lipoxygenase product is selected from the group consisting of: 13-HODE claim 1 , 15-HETrE claim 1 , 15-OHEPA claim 1 , 15-HETE claim 1 , and combinations thereof.11. 15-Hydroxy-5 claim 1 ,8 claim 1 ,11 claim 1 ,13-eicosatetraenoic acid lysine salt.12. A pharmaceutical composition comprising a salt form of a 15-lipoxygenase product.13. The pharmaceutical composition of further comprising an excipient.14. The pharmaceutical composition of claim 12 , wherein after storage for at least about 4 weeks claim 12 , the pharmaceutical composition comprises at least about 98% claim 12 , at least about 99% claim 12 , or about 100% of an initial amount of the salt form of the 15-lipoxygenase product.15. The pharmaceutical composition of claim 12 , wherein after storage for at least about 10 weeks or at least 24 weeks claim 12 , the pharmaceutical ...

Chiral Diacylhydrazine Ligands for Modulating the Expression of Exogenous Genes via an Ecdysone Receptor Complex

The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements. 125-. (canceled)27. The process of wherein B is 3 claim 26 ,5-di-methylphenyl.28. The process of wherein A is 2-ethyl-3-methoxyphenyl.29. The process of wherein Ris tert-butyl.30. (canceled)32. The method of claim 31 , wherein said ecdysone receptor complex is a chimeric ecdysone receptor complex and said DNA binding sequence further comprises a promoter.3335-. (canceled)36. The method of claim 31 , wherein the subject is a human.37. The method of claim 31 , wherein said cells are autologous cells.38. The method of claim 37 , wherein said autologous cells contain said ecdysone receptor complex and the DNA binding sequence for the ecdysone complex claim 37 , and said cells are implanted by injection into said subject to make it transgenic.39. (canceled)40. The method of claim 38 , wherein said injection is into a tumor.41. The method of claim 31 , wherein said ligand is administered to said transgenic subject as part of a pharmaceutical composition comprising a pharmaceutically acceptable carrier.42. The method of claim 41 , wherein said pharmaceutical composition is administered orally.43. The method of claim 41 , wherein said pharmaceutically acceptable carrier comprises a lipophilic solvent.45. (canceled)46. (canceled)47. The method of claim 31 , wherein said ecdysone receptor complex or ecdysone receptor ligand binding domain comprises a mutation ...

TRIFLUOROACETYL HYDRAZIDE COMPOUNDS AND MEDICAL USES THEREOF

The present invention relates to trifluoroacetyl hydrazide compounds and medical uses thereof. The compounds have a structure of the following formula: 2. The method of claim 1 , wherein the alkyl group is a lower alkyl group.4. The method of claim 1 , wherein the disease related to glutamate excitotoxicity is selected from the group consisting of Alzheimer's disease claim 1 , Parkinson's disease claim 1 , Huntington's disease claim 1 , muscular atrophic lateral sclerosis claim 1 , myasthenia gravis claim 1 , glaucoma claim 1 , senile dementia claim 1 , hyperthyroidism claim 1 , hypertension claim 1 , bronchial asthma claim 1 , type IV hyperlipoproteinemia claim 1 , and renal failure.5. The method of claim 1 , wherein the disease related to MEF2 disorder is selected from the group consisting of Parkinson's disease claim 1 , Alzheimer's disease claim 1 , dementia claim 1 , Huntington's disease claim 1 , muscular atrophic lateral sclerosis claim 1 , and myasthenia gravis.6. The method of claim 1 , wherein the disease related to oxidative stress injury or excessive free radicals generation is selected from the group consisting of stroke claim 1 , brain trauma claim 1 , epilepsy claim 1 , Parkinson's disease claim 1 , Huntington's disease claim 1 , amyotrophic lateral sclerosis claim 1 , Alzheimer's disease claim 1 , hypoxic-ischemic brain injury claim 1 , stroke claim 1 , dementia claim 1 , ischemic heart disease claim 1 , vascular thrombosis claim 1 , atherosclerosis claim 1 , hyperlipidemia claim 1 , emphysema claim 1 , cataract claim 1 , diabetes claim 1 , acute pancreatitis claim 1 , alcohol induced liver disease claim 1 , kidney damage and cancer.7. The method of claim 1 , wherein the disease related to neurodegeneration is selected from the group consisting of cerebral ischemia claim 1 , Parkinson's disease claim 1 , Alzheimer's disease claim 1 , amyotrophic lateral sclerosis claim 1 , ataxia telangiectasia claim 1 , bovine spongiform encephalopathy claim 1 , ...

Neprilysin inhibitors

In one aspect, the invention relates to compounds having the formula: where R 1 -R 6 , a, b, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Chiral Diacylhydrazine Ligands for Modulating the Expression of Exogenous Genes via an Ecdysone Receptor Complex

The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements. 125-. (canceled)27. The process of claim 26 , wherein B is 3 claim 26 ,5-di-methylphenyl.28. The process of claim 26 , wherein A is 2-ethyl-3-methoxyphenyl.29. The process of claim 26 , wherein Ris tert-butyl.3047-. (canceled)48. The process of claim 26 , wherein the chiral catalyst is a chiral phospholane catalyst complex.49. The process of claim 26 , wherein the compound of Formula II or Formula III has an enantiomeric excess of at least 95%.50. The process of claim 26 , wherein the compound of Formula III is:(R)—N′-(1-tert-Butyl-butyl)-N′-(3,5-dimethyl-benzoyl)-hydrazinecarboxylic acid benzyl ester;(R)—N′-(1-tert-Butyl-butyl)-N′-(3,5-dimethyl-benzoyl)-hydrazinecarboxylic acid tert-butyl ester;(R)-3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide;(R)-3,5-Dimethyl-benzoic acid N′-benzoyl-N-(1-tert-butyl-butyl)-hydrazide;(R)-3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-methyl-benzoyl)-hydrazide;(R)-3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-methoxy-benzoyl)-hydrazide;(R)-3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-fluoro-benzoyl)-hydrazide;(R)-3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-chloro-benzoyl)-hydrazide;(R)-3,5-Dimethyl-benzoic acid N′-(2-bromo-benzoyl)-N-(2-tert-butyl-butyl)-hydrazide;(R)-3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-3-methyl-benzoyl ...

Process for the preparation of N-alkyl-nitratoethylnitramines

The present invention relates to a continuous process for the preparation of N-alkyl-nitratoethylnitramines (e.g. NENA compounds, DINA). 3. The process according to claim 1 , characterised in that after the reactions the reaction mixture is brought into contact with water or an aqueous alkaline solution.4. The process according to claim 1 , characterised in that R is a methyl claim 1 , ethyl or butyl group or a group of the formula —CH—CH—O—NOand R′ is a methyl claim 1 , ethyl or butyl group or a group of the formula —CH—CH—OH.5. The process according to claim 1 , characterised in that the reactions are carried out in one or more continuous flow reactor(s).6. The process according to claim 1 , characterised in that the reactions are carried out in one or more tubular reactor(s).7. The process according to claim 1 , characterised in that the reactions are carried out in one or more microreactor(s).8. The process according to claim 1 , characterised in that the reactions are carried out at a pressure of from 0.5 bar above atmospheric pressure up to a pressure of 18 bar above atmospheric pressure.9. The process according to claim 1 , characterised in that the reaction with nitric acid is carried out at a temperature of from −20° C. to 30° C.10. The process according to claim 1 , characterised in that the reaction with a mixture of at least one acid anhydride and a chloride-containing catalyst is carried out at a temperature of from 20° C. to 60° C.11. The process according to claim 1 , characterised in that acetic anhydride is used as acid anhydride.12. The process according to claim 1 , characterised in that hydrogen chloride is used as chloride-containing catalyst.13. The process according to claim 1 , characterised in that the nitric acid used in the reaction is used with a concentration of from 75 to 96% in water.14. The process according to claim 1 , characterised in that a mixture of ethyl-NENA (R=ethyl) and methyl-NENA (R=methyl) is prepared.15. The process ...

PRODUCTION PROCESS FOR SELF-DISPERSIBLE PIGMENT, SELF-DISPERSIBLE PIGMENT, INK, INK CARTRIDGE AND INK JET RECORDING METHOD

The invention provides a production process for a self-dispersible pigment, having a step of bonding a group Rin the following general formula (1) to a particle surface of a pigment by radical addition reaction induced by removal of a hydrogen atom from a compound represented by the general formula (1): 3. The production process according to claim 1 , wherein Rhas at least one of a structure containing an arylene group and plural carboxylic acid groups and a structure containing an amide bond and a phosphonic acid group.4. The production process according to claim 1 , wherein the step is conducted in an aqueous system.5. The production process according to claim 1 , wherein the process is conducted at a temperature of 80° C. or less.6. A self-dispersible pigment produced by the production process according to .7. An ink comprising a self-dispersible pigment claim 6 , wherein the self-dispersible pigment is the self-dispersible pigment according to .8. An ink cartridge comprising an ink and an ink storage portion storing the ink claim 7 , wherein the ink comprises the ink according to .9. An ink jet recording method comprising ejecting an ink from a recording head of an ink jet system to record an image on a recording medium claim 7 , wherein the ink comprises the ink according to . 1. Field of the InventionThe present invention relates to a production process for a self-dispersible pigment, a self-dispersible pigment, an ink, an ink cartridge and an ink jet recording method.2. Description of the Related ArtA self-dispersible pigment is mainly produced by a chemical pigment-modifying technology. For example, Japanese Patent Application Laid-Open No. H10-510861 describes a process for obtaining a self-dispersible pigment by causing a pigment to react with a diazonium salt. In addition, Japanese Patent Application Laid-Open No. 2012-528917 describes a process for obtaining a self-dispersible pigment by subjecting a carbonyl group on a particle surface of a pigment and ...

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Vid behandling av hoegt blodtryck anvaendbara foereningar.

用于制备二肽基肽酶-iv抑制剂和中间体的改进方法

本发明涉及一种用于制备二肽基肽酶-IV抑制剂及中间体的改进方法。本发明通过采用低成本反应试剂能够降低制备成本，并通过提高产量而能够用于大量生产。

Enhanced preparation method of dipeptidyl peptidase-Ⅳ inhibitor and intermediates thereof

본 발명은 디펩티딜 펩티다아제-Ⅳ 저해제 및 중간체의 개량된 제조방법에 관한 것으로, 본 발명에 따른 제조방법은 반응시 저가의 시약을 사용함으로써 제조 비용을 절감할 수 있으며, 수율 또한 향상되어 대량 생산에 유용하게 사용될 수 있다. The present invention relates to an improved method for preparing dipeptidyl peptidase-IV inhibitors and intermediates. The method according to the present invention can reduce production costs by using low-cost reagents during the reaction, and yields are also improved for mass production. It can be usefully used.

Способы лечения протозойных инфекций

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2017 109 719 A (51) МПК A61K 31/155 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2017109719, 28.08.2015 (71) Заявитель(и): НЕОКЬЮЛИ ПТИ ЛТД (AU) Приоритет(ы): (30) Конвенционный приоритет: 02.09.2014 AU 2014903503 28 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 03.04.2017 AU 2015/000527 (28.08.2015) (87) Публикация заявки PCT: A WO 2016/033635 (10.03.2016) Адрес для переписки: 191002, Санкт-Петербург, а/я 5, Общество с ограниченной ответственностью "Ляпунов и партнеры" R U (57) Формула изобретения 1. Способ лечения или предупреждения протозойной колонизации или инфекции у субъекта, включающий стадию, в которой субъекту вводят терапевтически эффективное количество соединения Формулы I или его стереоизомера, таутомера, фармацевтически приемлемой соли или пролекарства, при этом протозойная инфекция вызвана протозойным агентом, где Формула I представляет собой: где R1 представляет собой Н, циклоалкил, Формулу II или Формулу III; Стр.: 1 A 2 0 1 7 1 0 9 7 1 9 (54) СПОСОБЫ ЛЕЧЕНИЯ ПРОТОЗОЙНЫХ ИНФЕКЦИЙ 2 0 1 7 1 0 9 7 1 9 (86) Заявка PCT: R U (43) Дата публикации заявки: 04.10.2018 Бюл. № (72) Автор(ы): ПЭЙДЖ Стефен (AU), СТИВЕНС Эндрю (AU), МАККЛАСКИ Адам (AU), КИНАН Мартина (AU), АБРАХАМ Ребекка (AU) где R3 выбран из группы, состоящей из: Н; NH2; NHNH2; O-СН2-СН3; NH-C(O)-фенила; NH-CH-хлорфенила; NH-хлорфенила; NH-CH2-хлорфенила; NH-N-СН-циклоалкила; N и R4 представляет собой CH-N-CH-CCl- и R4 связан с R3; Формулы IV; Формулы V; и Формулы VI; R U R U 2 0 1 7 1 0 9 7 1 9 A Стр.: 2 A A2 представляет собой N, С, NH, N-C(O)-фенил или Формулу VII, или (СН2)n, где n равен целому числу от 1 до 3, включительно; где A3, A4, A5, A6, A7, A8, A11, A12, A13, A14, A15, A16, A17, A18, A19, A20, A21 A23, A24, A25, A26 и A27 независимо представляют собой С, О, N, NH, S; где А9 представляет собой С, О, N, NH, N-C(O)-O-CH2-CH3, N-C(O)-O-СН(СН3)2, NC(O)-NH-CH2-CH3, N-C(O ...

一种生化制剂tmb的合成方法

本发明公开了一种生化制剂TMB的合成方法，包括如下步骤：1、2,2′,6,6′‑偶氮四甲苯胺‑N,N‑二氧化物的合成；2、2,2′,6,6′‑四甲基二苯肼的合成；3、TMB·(1/2)H 2 SO 4 的合成；4、TMB·2HCl的制备；5、TMB的制备。该方法合成路线简单，原料便宜易得，合成成本低，而且收率高。

Method of obtaining n',n'-disubstituted hydrazides

A process for preparing N',N'-disubstituted acid hydrazides by reacting N'-monosubstituted acid hydrazides with aldehydes in the presence of hydrogen and a hydrogenation catalyst is disclosed.

Circuit for reducing glitch of electronic volume

(57)【要約】 【課題】 不斉イミノアルドール反応等の不斉有機合成 を高い反応性と選択で触媒的に行うことを可能とする。 【解決手段】 ジルコニウム（IV）を触媒の活性中心原 子とし、２分子の光学活性なビナフチル基と酸素原子を 介して結合している構造の不斉ジルコニウム触媒を提供 する。

Amineimide composition

본 발명은 아민이미드 제조의 방법을 개시한다. 에폭시 화합물을, 3가 질소를 포함하는 히드라진, 및 무수물 작용성 물질 또는 카보닐 기 및 카보닐 기에 대해 알파-위치의 하나 이상의 헤테로원자를 포함하는 환형 화합물과 20℃ 초과의 온도에서 반응시켜 아민이미드 물질을 형성한다. 상기 에폭시 화합물 및 상기 무수물 작용성 물질 또는 상기 환형 화합물 중 하나 이상은 중합체성이다. 또한, 본원에서는 에폭시 화합물 및 하나 이상의 아민 작용기를 포함하는 화합물을 포함하는 접착제 조성물이 개시된다. 상기 하나 이상의 아민이미드 작용기를 포함하는 화합물은, 접착제 조성물의 총 중량을 기준으로 2 내지 8 중량%의 양으로 존재하고, 외부 에너지원에 의한 활성화시에 상기 에폭시 화합물과 반응한다. 상기 접착제 조성물은 또한 아미딘 염을 포함할 수 있다. The present invention discloses a method of preparing an amineimide. The epoxy compound is reacted with a hydrazine containing trivalent nitrogen, and an anhydride functional substance or a cyclic compound containing at least one heteroatom in the alpha-position to the carbonyl group and the carbonyl group at a temperature of more than 20°C to obtain an amine. Form a mid material. At least one of the epoxy compound and the anhydride functional material or the cyclic compound is polymeric. Also disclosed herein is an adhesive composition comprising an epoxy compound and a compound comprising at least one amine functional group. The compound containing at least one amineimide functional group is present in an amount of 2 to 8% by weight based on the total weight of the adhesive composition, and reacts with the epoxy compound upon activation by an external energy source. The adhesive composition may also include an amidine salt.

improved processes for hydrazide production

Aminimide compositions

FIELD: chemistry.SUBSTANCE: invention relates to a method of producing aminimide. Epoxy compound reacts with a hydrazine compound containing trivalent nitrogen and a cyclic compound containing a carbonyl group and at least one nitrogen or sulphur heteroatom located in the alpha position to a carbonyl group, or first oxygen heteroatom located in alpha position to carbonyl group, and second heteroatom of oxygen, nitrogen or sulphur, located in alpha position to carbonyl group, at temperature higher than 20 °C to form aminimide, where epoxy compound is polyepoxide. Present invention also describes an adhesive composition comprising an epoxy compound and a polymer compound containing at least two aminimide functional groups, said polymer compound is present in amount of 2–8 wt. % with respect to the total weight of the adhesive composition and reacts with the epoxy compound when activated by an external power source. Adhesive composition can also contain an aminimide salt.EFFECT: invention provides sufficient binding force and ease of application of adhesive composition when materials are connected to each other.14 cl, 3 tbl, 16 dwg РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 724 052 C2 (51) МПК C09D 163/00 (2006.01) C08G 59/40 (2006.01) C08G 59/44 (2006.01) C07C 319/02 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C09D 163/00 (2020.01); C08G 59/4014 (2020.01); C08G 59/4021 (2020.01); C08G 59/4035 (2020.01); C08G 59/4042 (2020.01); C08G 59/44 (2020.01); C07C 319/02 (2020.01) (21)(22) Заявка: 2018125032, 09.12.2016 09.12.2016 Дата регистрации: 19.06.2020 10.12.2015 US 14/964,748; 10.12.2015 US 14/964,795 (43) Дата публикации заявки: 23.01.2020 Бюл. № 3 (56) Список документов, цитированных в отчете о поиске: US 3628992 А, 21.12.1971. US 3485806 A, 23.12.1969. US 8430989 B2, 30.04.2013. EP 2199313 A1, 23.06.2010. (45) Опубликовано: 19.06.2020 Бюл. № 17 C 2 C 2 (85) Дата начала рассмотрения заявки PCT на ...

The synthesis technology of antioxidant 1024

本发明提供了一种有机合成抗氧化剂1024，即N，N′‑双[β(3，5‑二叔丁基‑4‑羟基苯基)丙酰]肼的合成方法，所述的制备方法包含以下步骤：首先以水合肼和β‑(3，5‑二叔丁基‑4‑羟基苯基)丙酸甲酯为原料合成β‑(3，5‑二叔丁基‑4‑羟基苯基)丙酰肼，然后再以β‑(3，5‑二叔丁基‑4‑羟基苯基)丙酰肼和乙酰乙酸乙酯为原料合成N，N′‑双[β(3，5‑二叔丁基‑4‑羟基苯基)丙酰]肼，本发明通过调整反应体系中溶剂的种类、反应物与另一种反应物的质量比以及反应物与溶剂的质量体积比，使反应进行的更加彻底，从而使产物产率得到了很大提高，并能保证在中试中产物产率依然可以高于现有水平。

PROCESS TO PREPARE A MIXTURE OF AZOALCANS, MATERIAL COMPOSITION AND GLOBAL STYLENE POLYMERIZATION PROCESS

Improved method of producing dipeptidyl peptidase-iv inhibitor and intermediate compound

FIELD: chemistry. SUBSTANCE: invention relates to an improved method of producing protected (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid of formula 2, as shown on dwg 1, and a dipeptidyl peptidase-IV inhibitor intermediate compound. The method involves: (step a) obtaining a compound of formula 6 by opening the epoxide ring in compound 5, using Grignard reagent; (step b) obtaining a compound of formula 7 by reacting the compound of formula 6 with sodium azide; (step c) obtaining a compound of formula 8 by reacting the compound of formula 7 with triphenyl phosphine and adding an amine protective group (PG); (step d) obtaining a compound of formula 9 by opening the aziridine ring in compound 8 using a cyanogens-based reagent; and (step e) obtaining a compound of formula 2 by hydrolysis of the compound of formula 9 using a base; [Reaction scheme 1] , where X denotes a halogen and PG denotes a protective group. Novel intermediate compounds are described. EFFECT: improved method. 12 cl, 3 dwg, 4 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 499 792 (13) C2 (51) МПК C07D C07D C07D C07C C07C 203/16 (2006.01) 203/24 (2006.01) 241/08 (2006.01) 213/02 (2006.01) 219/18 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2011141208/04, 30.03.2010 (24) Дата начала отсчета срока действия патента: 30.03.2010 (43) Дата публикации заявки: 10.05.2013 Бюл. № 13 2 4 9 9 7 9 2 R U (85) Дата начала рассмотрения заявки PCT на национальной фазе: 31.10.2011 C 2 C 2 (56) Список документов, цитированных в отчете о поиске: WO 2006/098342 A1, 21.09.2006. KR 20080094604, 23.10.2008. Bioorganic & Medicinal Chemistry Letters, (2007), 17(1), 49-52. Bulletin of the Korean Chemical Society (2008), 29(11), 2129-2134. US 2008-0280913 A1, 13.11.2008. EA 007434 B1, 27.10.2006. (86) Заявка PCT: KR 2010/001947 (30.03.2010) (87) Публикация заявки РСТ: WO 2010/114291 (07.10.2010) Адрес для переписки: 191036, Санкт-Петербург, а/я 24, "НЕВИНПАТ" (54 ...

Patent RU2017109719A3

7 ВУ"? 2017109719” АЗ Дата публикации: 18.01.2019 Форма № 18 ИЗИМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение Я «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2017109719/04(017045) 28.08.2015 РСТ/АО2015/00052/7 28.08.2015 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [ ] приоритета по первоначальной заявке № из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 2014903503 02.09.2014 АО Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) СПОСОБЫ ЛЕЧЕНИЯ ПРОТОЗОЙНЫХ ИНФЕКЦИЙ Заявитель: НЕЁОКЬЮЛИ ПТИ ЛТД, АЧ 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты мп см. Примечания [ ] приняты во внимание следующие пункты: р [ ] принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) Аб/1К 31/155 (2006.01) Аб1Р 33/02 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) Аб1К 31/155 Аб1Р 33/02 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы данных, использованные при поиске (название базы, и если, возможно, поисковые термины): Езрасепе, Соозе, Соо]е Ржеп$, РАТЕМТСОРЕ, Раб Срет, Ри Мед, Кеахуз, эслепсе Оиесё Уап4ех 6. ДОКУМЕНТЫ, ОТНОСЯЩИЕСЯ К ПРЕДМЕТУ ПОИСКА Кате- Наименование документа с указанием (где необходимо) частей, Относится к гория* относящихся к ...

Manufacture of hydrazinyl compounds useful in the manufacture of pyrazole carboxylic acid and derivatives, hydrazinyl compounds and their use

The present invention concerns the manufacture of hydrazinyl compounds useful in the manufacture of pyrazole carboxylic acid and derivatives thereof and processes for the manufacture of agrochemical or pharmaceutical compounds. The invention also concerns hydrazinyl compounds and their use.

Improved processes for making hydrazides

【課題】ヒドラジンおよび塩化アシルからヒドラジドを調製するための改善された合成方法を提供すること。【解決手段】（ａ）低温で、ヒドラジンおよび不活性溶媒を含む攪拌された実質的に均一なスラリーを調製するステップと、（ｂ）前記スラリーに塩化アシルを連続的に添加するステップとを含む、ヒドラジンおよび塩化アシルからヒドラジドを調製する方法が開示されている。この方法は、望ましくないビス−ヒドラジド副生成物の生成を回避しまたは制限する。この方法は、カリケアマイシンをモノクローナル抗体に結合するのに使用される分子である、３−メチル−３−メルカプトブタン酸ヒドラジドを調製するのに使用される。【選択図】なし

Method for allylation of N-acylhydrazone

Methods for preparing intermediate compounds for synthesis of pesticides

FIELD: organic chemistry, chemical technology, pesticides. SUBSTANCE: invention relates to the improved method for preparing compounds of the formula (I): wherein each R 1 and R 2 means independently halogen atom or its acid-additive salt that can be used in preparing the agricultural fungicide compound. Method involves hydrogenolysis of phenylhydrazine of the formula (II): wherein R 1 and R 2 are determined above or its acid-additive salt under reducing conditions using Raney nickel. Phenylhydrazine of the formula (II) or its acid-additive salt is prepared by reaction of compound of the formula (III) with hydrazine hydrate. EFFECT: improved preparing methods. 4 cl, 6 ex 2243207 С2 КО РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) (11) < . ‚(13) 57 МК’ С 07С 209/42, 211/52, 243/22 7 7 ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ИЗВЕЩЕНИЯ К ПАТЕНТУ НА ИЗОБРЕТЕНИЕ (21), (22) Заявка: 2001133265/04, 11.05.2000 (72) Автор(ы): АНСЕЛЬ Жан-Эрик (ЕВ), (24) Дата начала отсчета срока действия патента: ПЕРРЭН-ЖАНЕ Жилль (ЕВ), 11.05.2000 ЛЕРУА Пьер (ЕВ) (30) Конвенционный приоритет: (73) Патентообладатель(и): 13.05.1999 СВ 9911180.9 АВЕНТИС КРОПСАЙЕНС С.А. (ЕВ) (43) Дата публикации заявки: 10.07.2003 (74) Патентный поверенный: (45) Опубликовано: 27.12.2004 Назина Елена Евгеньевна (56) Список документов, цитированных в отчете о поиске: ($ 4508922А, 02.04.1985. ЦЗ 3903090А ‚02.09.1975. \О9511062А1,27.04.1995. ЦЗ 4343812 А, 10.08.1982. ВЕ 86948 1А, 05.02.1979. 4Р63-267783А2,04.11.1988. НОУВЕМ-ММЕМЕ. Мешподеп аег Огдатзспеп Спетг. 1990,Вапа Е1ба, р.648-653. НОЧВЕМ-ММЕУЕ. Ме@Подеп адег Огдап!$свеп Спет. 1990,Вапа Е1 64, р.985-986. (см. прод.) (85) Дата перевода заявки РСТ на национальную фазу: 13.12.2001 (86) Заявка РСТ: ЕР 00/04595 (11.05.2000) (87) Публикация РСТ: М/О 00/69805 (23.11.2000) Адрес для переписки: 129010, Москва, ул. Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Е.Е.Назиной (54) СПОСОБЫ ПОЛУЧЕНИЯ ПРОМЕЖУТОЧНЫХ ...

Method for synthesizing pyraclostrobin intermediate

本发明公开了一种合成吡唑醚菌酯中间体的方法，所述合成方法包括：用对溴氯苯、水合肼为反应原料制得的对氯苯肼盐酸盐，制备得到中间产物1‑（4‑氯苯基）‑3‑吡唑醇；用邻硝基甲苯、氯气，在催化剂存在的情况下反应制得邻硝基氯化苄；将上述1‑（4‑氯苯基）‑3‑吡唑醇与邻硝基氯化苄进行醚化反应，获得吡唑醚菌酯中间体，即醚化产物2‑[(N‑4‑氯苯基)‑3‑吡唑氧基甲基]硝基苯。本发明合成方法能大幅降低对氯苯肼盐酸盐合成过程中产生的废水量，降低安全隐患；以对氯苯肼盐酸盐为原料，可实现中间产物1‑（4‑氯苯基）‑3‑吡唑醇HPLC含量≥98%，收率≥90%的生产效果；用氯气替代溴素或氢溴酸制备邻硝基溴化苄，生产成本和环保压力得到控制；可制备得到含量≥98%，产率≥90%的醚化产物。

Method of producing unsymmetrical dimethylhydrazine

FIELD: chemistry. SUBSTANCE: invention relates to a method of producing asymmetric dimethylhydrazine, involving production of methylamines, recovery of dimethylamine, nitrosation thereof, recovering the obtained nitrosodimethylamine followed by hydrogenation thereof and separating commercial UDMH, wherein step of producing dimethylamine is carried out in molar ratio of methyl groups to amino groups of not more than 0.5, and nitrosodimethylamine hydrogenation is carried out in the displacing flooded mode with volume ratio of the gas and liquid phases flows of not less than 3,000, with the contact load on the catalyst by the liquid phase from 0.2 (h) -1 up to 0.5 (h) -1 , density of gas phase flow in hydrogenation reactor from 3 to 10 nm 3 /m 2 ⋅with, at reaction mass temperature of not more than 40 °C. After that separation of products of stage of dimethylamine production is carried out by azeotropic rectification with extraction of commercial product in five stages in the following order: distillation of ammonia and trimethylamine azeotrope and their recycling; distillation of monometilamine and trimethylamine azeotrope and their recycling; monomethylamine distillation and recycling thereof; distillation of dimethylamine and its supply to the nitrosation stage; distillation of methanol and residual methylamines and their recycling. EFFECT: there is created a closed stage of obtaining methylamines, where, along with extraction of target dimethylamine from the reaction mixture, return to the stage of synthesis of mixtures consisting of ammonia, monomethylamine and trimethylamine, without separation of these products; returned (recycled) products react again with ammonia, increasing yield of dimethylamine. 4 cl, 2 dwg, 19 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 687 064 C1 (51) МПК C07C 241/02 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07C 241/02 (2019.02) (21) (22) Заявка: 2018136685, 17.10.2018 (24) ...

Compound having heterocyclic skeleton and method for producing optically active compound using said compound as asymmetric catalyst

METHODS FOR TREATING PROTOZOIC INFECTIONS

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2020 113 652 A (51) МПК A61K 31/155 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2020113652, 28.08.2015 (71) Заявитель(и): НЕОКЬЮЛИ ПТИ ЛТД (AU) Приоритет(ы): (30) Конвенционный приоритет: (43) Дата публикации заявки: 10.06.2020 Бюл. № 16 (72) Автор(ы): ПЭЙДЖ Стефен (AU), СТИВЕНС Эндрю (AU), МАККЛАСКИ Адам (AU), КИНАН Мартина (AU), АБРАХАМ Ребекка (AU) R U (57) Формула изобретения 1. Способ лечения или предупреждения протозойной колонизации или инфекции у субъекта, включающий стадию введения терапевтически эффективного количества соединения или его фармацевтически приемлемой соли, выбранного из группы, состоящей из: 4,6-бис(2((E)-1-(4-хлорфенил)этилиден)гидразинил)пиримидина (NCL178); 4,6-бис(2((E)-4-хлорбензилиден)гидразинил)пиримидин-2-амина (NCL179); (2Z,2'Z)-2,2'-(пиримидин-4,6-диилбис(гидразин-2-ил-1-илиден))бис(2-(4-хлорфенил) этан-1-ола) (NCL180); 4,6-бис(2-((E)-4-хлорбензилиден)гидразинил)пиримидина (NCL181); 6-хлор-N4-(1-фенилэтил)пиримидин-2,4-диамина (NCL182); N4,N6-бис(1-фенилэтил)пиримидин-4,6-диамина (NCL183); N4,N6-бис(1-фенилэтил)пиримидин-2,4,6-триамина (NCL184); 4,6-бис(2-((E)-1-(4-хлорфенил)этилиден)гидразинил)пиримидин гидрохлорида (NCL185); 4,6-бис(2-((E)-4-хлорбензилиден)гидразинил)пиримидин гидрохлорида (NCL187); (2Z,2'Z)-2,2'-(пиримидин-4,6-диилбис(гидразин-2-ил-1-илиден))бис(2-(4-хлорфенил) этан-1-ол) гидрохлорида (NCL189); 4,6-бис(2-((E)-4-бромбензилиден)гидразинил)пиримидин-2-амина (NCL193); N',N'''-(2-аминопиримидин-4,6-диил)ди(бензoгидрaзида) (NCL194); 4,6-бис(2-((E)-4-метилбензилиден)гидразинил)пиримидин-2-амина (NCL195); 4,4'-((1E,1'E)-((2-аминопиримидин-4,6-диил)бис(гидразин-2-ил-1-илиден))бис (метанилилиден))дифенола (NCL196); 3,3'-((1E,1'E)-((2-аминопиримидин-4,6-диил)бис(гидразин-2-ил-1-илиден))бис Стр.: 1 A 2 0 2 0 1 1 3 6 5 2 A (54) СПОСОБЫ ЛЕЧЕНИЯ ПРОТОЗОЙНЫХ ИНФЕКЦИЙ 2 0 2 0 1 1 3 6 5 2 Адрес для переписки: 191002, Санкт- ...

Novel curing agent and degradable polymer and composite based thereon

The continuous preparation method of diazonium salt of aniline and phenylhydrazine hydrochloride based on microreactor

一种基于微反应器的苯胺重氮盐连续制备方法，在将常温配置的苯胺盐和酸混合物及亚硝酸盐水溶液连续注入微反应器内进行重氮化反应，然后再经还原步骤，经由酸析、过滤后得到盐酸苯肼。本发明操作简单，重氮化反应温度高，反应物用量接近化学计量比，重氮化反应时间短，产率高，可连续化生产苯胺重氮盐及和盐酸苯肼，减少能耗，增加过程安全性，可用于工业化生产。

Process for producing acylhydrazones of formylacetic acid ester

A process is provided for production of acylhydrazones of formyl-acetic acid ester of the general formula <IMAGE> wherein R1 is an alkyl group with from 1 to 6 carbon atoms and R2 is an alkoxy group or an amino group. A propiolic acid ester of the general formula H-C 3BOND C-COOR1 is contacted with hydrazine derivatives of the general formula H2N-NH-CO-R2 in the presence of a solvent such as water or a lower alcohol. The resulting products are technically valuable starting materials for the production of biocides, for example of 1,2,3-thiadiazole derivatives.

AMINIMIDE COMPOSITIONS

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2018 125 032 A (51) МПК C09D 163/00 (2006.01) C08G 59/40 (2006.01) C08G 59/44 (2006.01) C07C 319/02 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2018125032, 09.12.2016 (71) Заявитель(и): ППГ ИНДАСТРИЗ ОГАЙО, ИНК. (US) Приоритет(ы): (30) Конвенционный приоритет: 10.12.2015 US 14/964,748; 10.12.2015 US 14/964,795 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 10.07.2018 US 2016/065866 (09.12.2016) (87) Публикация заявки PCT: WO 2017/100602 (15.06.2017) A Адрес для переписки: 109012, Москва, ул. Ильинка, 5/2, ООО "Союзпатент" R U (57) Формула изобретения 1. Клеевая композиция, содержащая: эпокси-соединение; и соединение, содержащее по меньшей мере одну аминимидную функциональную группу, где соединение, содержащее по меньшей мере одну аминимидную функциональную группу, реагирует с эпокси-соединением при активации внешним источником энергии; где соединение, содержащее по меньшей мере одну аминимидную функциональную группу присутствует в количестве 2-8% мас. в расчете на общую массу клеевой композиции. 2. Клеевая композиция по п. 1, содержащая: эпокси-соединение; и полимерное соединение, содержащее по меньшей мере две аминимидные функциональные группы, где указанное полимерное соединение реагирует с эпоксисоединением при активации внешним источником энергии; где указанное полимерное соединение присутствует в количестве 2-8% мас. в расчете на общую массу клеевой композиции. 3. Клеевая композиция по п. 2, в которой полимерное соединение представляет собой продукт реакции реагентов, включающих полиэпоксид, гидразин, содержащий трехвалентный азот, и реагент, содержащий карбонильную группу. 4. Клеевая композиция по п. 1, содержащая: Стр.: 1 A 2 0 1 8 1 2 5 0 3 2 (54) АМИНИМИДНЫЕ КОМПОЗИЦИИ 2 0 1 8 1 2 5 0 3 2 (86) Заявка PCT: R U (43) Дата публикации заявки: 23.01.2020 Бюл. № 3 (72) Автор(ы): ЧАО, Тьен-Чих (US), НАКАДЗИМА, Масаюки (US), ЧЖОУ, Хунин (US), СВАРУП ...

Cathecol Hydrazine Derivatives, Process for Producing the Same and Pharmaceutical Composition Containing the Same

본 발명은 포스포디에스터라제 IV 또는 종양괴사인자(TNF: tumor necrosis factor)에 억제작용을 갖는 하기 화학식(I)의 신규한 캐테콜 히드라진 유도체 및 그의 염, 이의 제조방법 및 그를 유효성분으로 함유한 약제학적 조성물에 관한 것이다: The present invention is a novel catechol hydrazine derivative of formula (I) and salts thereof having an inhibitory effect on phosphodiesterase IV or tumor necrosis factor (TNF), a method for preparing the same and an active ingredient thereof One pharmaceutical composition relates to: (I) (I) 상기식에서, Where R 1 는 (C 1 -C 7 )알킬 또는 (C 3 -C 7 )사이클로알킬이고, R 1 is (C 1 -C 7 ) alkyl or (C 3 -C 7 ) cycloalkyl, R 2 는 i) -(C 1 -C 5 )알킬; ⅱ) -CN; R 2 is i)-(C 1 -C 5 ) alkyl; Ii) -CN; ⅲ) [여기서, A는 탄소 또는 질소이며, R 5 는 a) -수소, b) -(C 1 -C 3 )알킬, c) -히드록시(C 1 -C 3 )알킬, d) -CO 2 H, e) -CH=N-OH, f) -테트라졸릴 또는 g) -C(=O)-R 6 이고, 여기서, R 6 는 산소, 황 및 질소 중에서 동일하거나 상이한 1개 또는 2개를 함유하면서 C 3 -C 4 로 연결된 고리화합물 또는 (C 1 -C 4 )알킬아민이다]; ⅳ) 할로겐 화합물; 또는 ⅴ) -F, -Cl 및 -Br 중에서 동일하거나 상이한 1개 내지 3개로 치환된 (C 1 -C 4 )알킬이고, Ⅲ) [Wherein A is carbon or nitrogen, R 5 is a) -hydrogen, b)-(C 1 -C 3 ) alkyl, c) -hydroxy (C 1 -C 3 ) alkyl, d) -CO 2 H e) -CH = N-OH, f) -tetrazolyl or g) -C (= 0) -R 6 , wherein R 6 contains one or two of the same or different among oxygen, sulfur and nitrogen While being a cyclic compound or (C 1 -C 4 ) alkylamine linked by C 3 -C 4 ; Iii) a halogen compound; Or iii) (C 1 -C 4 ) alkyl substituted with one to three, which is the same or different among -F, -Cl and -Br, R 3 및 R 4 는 독립적으로 ⅰ) -H; ⅱ) -(C 1 -C 7 )알킬; ⅲ) -C(=B)-R 7 [여기서 B는 O, S 또는 N-R 8 이며, R 7 는 a) -(C 1 -C 7 )알킬, b) -NHR 8 (여기서, R 8 는 -H, -OH, -NH2, -(C 1 -C 5 )알콕시, -(C 1 -C 5 )알킬, 피리딜 또는 페닐기이다), c) -C(=O)NH 2 또는 d) 할로겐, 니트릴, 트리플로로메틸, (C 1 -C 6 )알킬 또는 카르복실산기로 치환된 2-, 3- 또는 4-피리딜, 피리미딜 또는 페닐기이다]; ⅳ) 할로겐, (C 1 -C 6 ) 알콕시, 니트릴, 트리플로로메틸, (C 1 -C 6 )알킬 및 카르복실산기 중에서 동일하거나 상이한 1개 또는 2개로 치환된 2-, 3- 또는 4-피리딜, 피리미딜 또는 페닐기; 또는 ⅴ) 산소, 황 또는 질소를 함유하는 C 3 -C 4 로 직접 연결된 고리화합물이다. R 3 and R 4 are independently iii) -H; Ii)-(C 1 -C 7 ) alkyl; Iii) -C (= B) -R 7 where B is O, S or NR 8 , where R 7 is a)-(C ...

A kind of anthraquinone derivative

本发明公开了一种蒽醌衍生物，属于荧光检测领域。该方法是通过化合物Ⅰ在氧化剂的作用下进行氧化反应，制备得到化合物Ⅱ；在酸性环境下，化合物Ⅱ与乙醇进行酯化反应，得到化合物Ⅲ；在加热回流的条件下，化合物Ⅲ与水合肼进行反应，得到化合物Ⅳ；在惰性气体保护的环境下，化合物Ⅳ与异硫氰酸苯酯进行反应，得到化合物Ⅴ。本发明所提供的制备方法简单，易于工业化生产。且制备得到的多信号探针对汞离子的检出限低且选择性高。

Preparation method of hydrazino ethyl acetate hydrochloride

本发明公开了一种肼基乙酸乙酯盐酸盐的制备方法，属于有机合成技术领域。本发明的技术方案要点为：利用氯乙酸乙酯或溴乙酸乙酯为起始物料，经与肼基甲酸叔丁酯反应上叔丁基保护基，脱保护，成盐酸盐，制得肼基乙酸乙酯盐酸盐。本发明具有反应条件温和、收率高、纯度高、成本低、经济环保和适用于产业化等优点，是一种具有工业生产价值的合成方法。

Method for allylation of N-acylhydrazone

【課題】エナンチオ選択的にアリル化されたＮ−アシルヒドラゾンが効率的に得られる、新規なＮ−アシルヒドラジンのアリル化方法の提供。【解決手段】一般式［１］【化２３】［式中、Ｒ０は置換基を有していてもよい炭化水素基、同複素環基又は−ＣＯＯＲ１（但し、Ｒ１は炭化水素基を表す。）を表し、Ｒ２はアシル基を表す。］で示されるＮ−アシルヒドラゾンと、例えば、アリルトリクロロシランやクロチルトリクロロシラン等のアリル化試薬とを、キラルホスフィンオキシド類の存在下で反応させることを特徴とする、一般式［３］【化２４】（式中、Ｒ０及びＲ２は前記と同じ。Ｒ３、Ｒ４は共に水素原子を表すか、或いは一方が水素原子で、他方は炭化水素基を表す。Ｒ５、Ｒ６はそれぞれ独立して水素原子又は炭化水素基を表す。）で示される、エナンチオ選択的にアリル化されたＮ−アシルヒドラジンの製造法。【選択図】 なし The present invention provides a novel method for allylation of N-acylhydrazine, which can efficiently obtain an enantiomerically allylated N-acylhydrazone. [Means for Solution] [wherein R0 represents a hydrocarbon group, a heterocyclic group, or -COOR1 which may have a substituent (wherein R1 represents a hydrocarbon group). And R2 represents an acyl group. ], And an allylation reagent such as allyltrichlorosilane and crotillytrichlorosilane in the presence of a chiral phosphine oxide, and a general formula [3] (Wherein R0 and R2 are the same as above. R3 and R4 both represent a hydrogen atom, or one is a hydrogen atom and the other is a hydrocarbon group. R5 and R6 are each independently hydrogen. Represents an atom or a hydrocarbon group). [Selection figure] None

A kind of process for cleanly preparing of methyl hydrazine

本发明公开了一种甲基肼的清洁生产工艺，包括以下步骤(1)以一盐酸肼为起始原料，加入盐酸和甲醇进行甲基化反应，生成甲基肼盐酸盐，加入甲醇析晶后，降温分离出盐酸肼(2)滤液蒸馏回收甲醇后，加入水合肼游离，并反复加入水减压蒸馏带出甲基肼，所得馏分精馏得甲基肼；(3)蒸馏底物再加入甲醇分离出盐酸肼，母液蒸馏回收甲醇后的釜残直接套用至游离过程。本发明方法避免了水合肼和盐酸制备盐酸肼导致的水分引入和高温脱水过程，避免了产品分解，降低了能耗；既保证了后期游离的效果，同时还保证了甲基肼的收率；减少水合肼用量同时又保证了游离完全；解决了原料累积情况，解决了过多副产物盐酸肼无法消化的难题。

For the preparation of improving one's methods of the intermediate of dipeptidyl peptidase-iv inhibitor

本发明涉及一种用于制备二肽基肽酶-IV抑制剂的中间体的改进方法。本发明通过采用低成本反应试剂能够降低制备成本，并通过提高产量而能够用于大量生产。

Preparation method of prothioconazole intermediate

本发明公开一种丙硫菌唑中间体的制备方法，其包括如下步骤：（1）使邻氯苯乙酸进行酰氯化反应生成化合物I，所述X选自氟、氯、溴或碘；（2）使丙二酸二甲酯与无机碱反应生成化合物Ⅱ；（3）使所述化合物I、化合物Ⅱ反应生成化合物Ⅲ；（4）使化合物Ⅲ先经过环丙烷化反应生成化合物Ⅳ，然后再经过水解脱羧反应生成化合物Ⅴ；（5）使化合物Ⅴ进行氯代反应生成丙硫菌唑中间体。本发明的制备方法避免了格氏试剂的使用，无需在苛刻的无水无氧的条件下进行，降低了生产的安全隐患；本发明的制备方法使用的原料价格便宜，降低了丙硫菌唑中间体的制备成本，适用于工业化生产。

Chiral diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements.

Crystalline diacylhydrazine and the use thereof

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject.

Preparation of alkylhydrazines

This application relates to a process for preparing alkylhydrazines from an alkene and hydrazine with an acid catalyst. More particularly, it relates to a process for preparing t-butylhydrazine from hydrazine and isobutylene in aqueous acid.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising; the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.

Chiral diachylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex

The present invention provides diacylhydrazine ligands and chiral diacylhydrazine ligands for use with ecdysone receptor-based inducible gene expression systems. Thus, the present invention is useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable. An advantage of the present invention is that it provides a means to regulate gene expression and to tailor expression levels to suit the user's requirements.

Crystalline diacylhydrazine and the use thereof

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject.

Crystalline diacylhydrazine and the use thereof

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject.

Crystalline diacylhydrazine and the use thereof

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N'-(2-ethyl-3-methoxybenzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N'-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject.

Crystalline diacilhydrazine and its application

FIELD: biotechnology. SUBSTANCE: invention relates to a novel crystalline form III of N-(1-t-butylbutyl)-N'-(2-ethyl-3-methoxybenzoyl)-hydrazide(R)-3,5-dimethylbenzoic acid. The present invention also provides compositions comprising a crystalline Form III, a method for its obtaining and usage in order to regulate gene expression in cell or in subject. EFFECT: improved properties of compounds. 20 cl, 32 dwg, 12 tbl, 17 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 629 113 C2 (51) МПК C07C 243/38 (2006.01) C12N 15/09 (2006.01) A61K 31/166 (2006.01) A61P 35/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2014111288, 07.09.2012 (24) Дата начала отсчета срока действия патента: 07.09.2012 Дата регистрации: (73) Патентообладатель(и): ИНТРЕКСОН КОРПОРЕЙШН (US) Приоритет(ы): (30) Конвенционный приоритет: 08.09.2011 US 61/532,368 (56) Список документов, цитированных в отчете о поиске: RU 2009145642 A, 29.05.2008. WO 2004078924 A2, 16.09.2004. (45) Опубликовано: 24.08.2017 Бюл. № 24 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 08.04.2014 (86) Заявка PCT: US 2012/054141 (07.09.2012) (87) Публикация заявки PCT: 2 6 2 9 1 1 3 (43) Дата публикации заявки: 20.10.2015 Бюл. № 29 R U 24.08.2017 (72) Автор(ы): ХОРМАНН Роберт Е. (US), ШУЛЬМАН Инна (US), РОДЕЛ Ева (US), ХИЛФАЙКЕР Рольф (US), ДЕПОЛ Сьюзан М. (US) Адрес для переписки: 190000, Санкт-Петербург, ВОХ 1125, "ПАТЕНТИКА" (54) КРИСТАЛЛИЧЕСКИЙ ДИАЦИЛГИДРАЗИН И ЕГО ПРИМЕНЕНИЕ (57) Реферат: Изобретение относится к новой содержащие кристаллическую форму III, способ кристаллической форме III N-(1-трет-бутилбутил) ее получения и применения для регуляции -N'-(2-этил-3-метоксибензоил)-гидразида (R)-3,5экспрессии генов в клетке или в субъекте. 7 н. и диметилбензойной кислоты. В настоящем 13 з.п. ф-лы, 32 ил., 12 табл., 17 пр. изобретении также предложены композиции, R U 2 6 2 9 1 1 3 C 2 C 2 WO 2013/036758 (14.03.2013) Стр.: 1 RUSSIAN FEDERATION (19 ...

CRYSTALLINE DIACYLHYDRAZIN AND ITS APPLICATION

1. Кристаллический N-(1-трет-бутилбутил)-N′-(2-этил-3-метоксибензоил)-гидразид (R)-3,5-диметилбензойной кислоты или кристаллический N-(1-трет-бутилбутил)-N′-(2-этил-3-метоксибензоил)-гидразид (S)-3,5-диметилбензойной кислоты, включающие Форму III, Форму IV, Форму V, Форму VI, Форму VII, Форму VIII, или Форму IX, или их смесь, где:Форма III характеризуется дифрактограммой порошковой рентгеновской дифракции, содержащей пики при 8,14, 8,52, 9,62, 11,02, 11,90, 12,16, 14,02, 14,62, 17,00, 17,88, 18,56, 19,02, 19,24, 20,51, 20,93, 22,19, 22,73, 23,22, 24,31, 24,53, 25,91, 26,22, 27,36, 27,73, 28,70, 30,84, 31,52, 32,30, 33,19 и 34,39 градусах 2Θ;Форма IV характеризуется дифрактограммой порошковой рентгеновской дифракции, содержащей пики при 6,83, 8,38, 8,91, 10,11, 10,31, 11,30, 11,89, 12,18, 12,98, 13,69, 14,14, 15,11, 15,81, 16,23, 17,60, 17,99, 18,60, 19,15, 19,66, 20,28, 20,70, 21,15, 21,68, 22,44, 22,71, 23,50, 23,79, 24,06, 24,86, 25,55, 26,53, 26,94, 27,21, 27,60, 28,67, 29,79, 30,50, 30,75, 31,55, 31,89, 32,78, 33,25, 33,48, 33,81 и 34,68 градусах 2Θ;Форма V характеризуется дифрактограммой порошковой рентгеновской дифракции, содержащей пики при 9,38, 12,22, 13,18, 14,98, 17,32, 18,40, 22,41, 23,40, 23,55, 24,63, 24,79, 25,61, 28,02 и 31,77 градусах 2Θ;Форма VI характеризуется дифрактограммой порошковой рентгеновской дифракции, содержащей пики при 9,38, 12,23, 13,25, 17,48, 18,41 и 22,41 градусах 2Θ;Форма VII характеризуется дифрактограммой порошковой рентгеновской дифракции, содержащей пики при 8,18, 9,71, 13,30, 16,22, 17,73, 20,98, 21,20, 22,76, 24,68, 26,72 и 29,39 градусах 2Θ;Форма VIII характеризуется дифрактограммой порошковой рентгеновской дифракции, содержащей пики при 10,05, 10,77, 14,06, 16,76, 18,11, 18,32, 18,43, 20,89, 21,71, 21,87, 24,07, 24,90 и 28,71 градусах 2Θ; иФорма IX характеризуется дифрактограммой порошковой рентгеновской дифракции, содержащей пики при 7,06, 15,74 и 18,71 градусах 2Θ.2. N-(1-трет-бутилбутил)-N′-(2-этил-3-метоксибензоил)- ...

Method for preparing dinitrodiazaalkanes and intermediate substances

FIELD: organic chemistry, chemical technology. SUBSTANCE: invention relates to a method for preparing dinitrodiazaalkanes that can be used in producing gun powders used for warhead charges. Invention describes a method for preparing dinitrodiazaalkanes from alkylamines and esters in the following reactions: (1) dicarboxylic acid ester is subjected for interaction with alkylamine in an aqueous medium to form the corresponding dicarboxylic acid dialkyldiamide; (2) prepared dialkyldiamide is nitrated with usual nitrating agent to the corresponding dicarboxylic acid dialkyldinitroamide; (3) prepared dialkyldinitroamide is converted to the corresponding alkylnitroamine by mixing dialkyldinitroamide with methyl- and/or ethylamine in an aqueous medium and formed dimethyl- and/or diethylamide of dicarboxylic acid are separated and remaining substance is acidified and alkylnitroamine is extracted; (4) isolated alkylnitroamine is condensed to dinitrodiazaalkanes spontaneously by the known method. Invention provides the development of industrial method for preparing dinitrodiazaalkanes that is carried out easily and without enhanced consumptions and large risk. EFFECT: improved preparing method. 13 cl ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß RU (19) (11) 2 274 637 (13) C2 (51) ÌÏÊ C07C 243/02 (2006.01) C07C 241/00 (2006.01) C06B 25/34 (2006.01) ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÎÏÈÑÀÍÈÅ ÈÇÎÁÐÅÒÅÍÈß Ê ÏÀÒÅÍÒÓ (21), (22) Çà âêà: 2001132633/04, 02.03.2001 (72) Àâòîð(û): ÊÍÎÒÒ Òîìàñ (DE) (24) Äàòà íà÷àëà îòñ÷åòà ñðîêà äåéñòâè ïàòåíòà: 02.03.2001 (73) Ïàòåíòîîáëàäàòåëü(è): ÍÈÒÐÎÕÅÌÈ ÀØÀÓ ÃÌÁÕ (DE) (30) Ïðèîðèòåò: 02.03.2000 (ïï.1-13) DE 10010190.9 R U (43) Äàòà ïóáëèêàöèè çà âêè: 10.07.2003 (45) Îïóáëèêîâàíî: 20.04.2006 Áþë. ¹ 11 2 2 7 4 6 3 7 (56) Ñïèñîê äîêóìåíòîâ, öèòèðîâàííûõ â îò÷åòå î ïîèñêå: US 4476322 À, 09.10.1984. US 4469888 À, 04.09.1984. SU 1616905 A1, 30.12.1990. (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 03.12.2001 (86) Çà âêà ...

Neprilysin inhibitors

FIELD: pharmacology. SUBSTANCE: invention relates to formula I compounds, or pharmaceutically acceptable salts thereof, which have the ability to inhibit neprilysin activity (NEP). In formula I, R 1 is selected from H, -C 1 - 8 alkyl, -C 1 - 6 alkylene-OC(O)R 10 , -CH 2 -pyridinyl, -(CH 2 ) 2 -pyridinyl and ; R 10 is selected from -C 1 - 6 alkyl, -OC 1 - 6 alkyl and -CH(R 15 )-NHC(O)O-C 1 - 6 alkyl; R 14 is -C 1 - 6 alkyl; R 15 is -CH(CH 3 ) 2 ; R 2 is -OR 21 or -CH 2 OR 21 ; and R 3 is H or -CH 3 ; where R 21 is H; or R 2 is taken with R 3 to form -CH 2 -CH 2 -; Z is selected from -CH- and -N-; R 4 is selected from H, -C 1 - 8 alkyl, -C 1 - 3 alkylene-O-C 1 - 8 alkyl, -C 1 - 3 alkylene-C 6 - 10 aryl, -[(CH 2 ) 2 O] 1 - 3 CH 3 and ; R 44 is-C 1 - 6 alkyl; A is 0 or 1; R 5 is selected from halogen, -CH 3 , -CF 3 and -CN; b is 0 or an integer of 1 to 3; each R 6 are independently selected from halogen, -OH, -CH 3 , -OSN 3 , -CN and -CF 3 . Each alkyl group in R 1 and R 4 is optionally substituted with 1 to 8 fluorine atoms and the methylene linker on biphenyl is optionally substituted with one or two -C 1 - 6 alkyl groups. The invention also relates to a method for the preparation of formula I compounds containing their pharmaceutical composition and application of the said compounds for preparation of a medicament for treatment of hypertension, heart failure or kidney disease. EFFECT: improved compounds properties. 40 cl, 16 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 629 930 C2 (51) МПК C07C 233/56 (2006.01) C07C 243/26 (2006.01) C07C 271/22 (2006.01) C07C 231/02 (2006.01) C07C 241/04 (2006.01) C07D 317/40 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА A61K 31/216 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ A61K 31/27 (2006.01) A61K 31/365 (2006.01) A61P 9/00 (2006.01) (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2014122109, 01.11.2012 (24) Дата начала отсчета срока действия патента: 01.11.2012 05.09.2017 R U Дата регистрации: (72) Автор(ы): ХЬЮЗ Адам (US), ФЕНСТЕР Эрик (US), ...

Process for Producing Hydrazone Compound

본 발명은 하기 화학식 3으로 표시되는 히드라진 화합물을 반응기 밖으로 취출하지 않고, 하기 화학식 4로 표시되는 카르보닐 화합물과 축합시키는 공정을 포함하는, 하기 화학식 5로 표시되는 히드라존 화합물의 제조 방법을 제공한다. 본 발명에 따르면, 구조상 불안정하고, 또한 그 독성(변이원성)에 의해 작업자에 대한 안전성 상의 영향을 미칠 것이 염려되는 반응 중간체인 히드라진 화합물을 반응기로부터 일체 취출하지 않고, 목적으로 하는 히드라존 화합물을 고품질 또한 고수율로 얻을 수 있다. The present invention provides a method for producing a hydrazone compound represented by the following Chemical Formula 5, including a step of condensing a hydrazine compound represented by the following Chemical Formula 3 with a carbonyl compound represented by the following Chemical Formula 4 without taking out of the reactor; . According to the present invention, the hydrazine compound, which is structurally unstable and whose reaction intermediate is concerned that the toxicity (mutagenicity) may have a safety impact on the worker, is not taken out from the reactor at all, and the desired hydrazone compound can be obtained in high quality. It can be obtained in high yield. <화학식 3> <Formula 3> <화학식 4> &Lt; Formula 4 > <화학식 5> &Lt; Formula 5 >

Enkephalinase inhibitor

本发明的一方面涉及具有式(I)的化合物： 其中R 1 到R 6 、a、b和Z如本说明书中所定义，或者是其医药上可接受的盐。这些化合物具有脑啡肽酶抑制活性。另一方面，本发明涉及包含所述化合物的医药组合物、使用所述化合物的方法以及制备所述化合物的方法和中间物。

n- (2-isopropyl acid) p-hydroxybenzoyl hydrazone lead complex as well as preparation method and application thereof

本发明公开了具有一维链状结构的N‑(2‑异丙酸)对羟基苯甲酰腙铅配合物及其制备方法和其在生物抑菌方面的应用。该铅配合物的制备方法为：先将4‑羟基苯甲酸甲酯和水合肼在有机溶剂中加热回流反应，然后将上述产物和丙酮酸在有机溶剂中加热回流反应得N‑(2‑异丙酸)对羟基苯甲酰腙，最后将铅盐与N‑(2‑异丙酸)对羟基苯甲酰腙的甲醇溶液反应得N‑(2‑异丙酸)对羟基苯甲酰腙铅配合物。试验结果表明：该铅配合物对腐皮镰刀菌、丹参枯萎病菌具有良好的抑菌活性，特别是针对腐皮镰刀菌抑菌效果尤为突出，具有广阔的应用前景。

Improved method for preparing dipeptidyl peptidase-iv inhibitor and intermediate

本发明涉及一种用于制备二肽基肽酶-IV抑制剂及中间体的改进方法。本发明通过采用低成本反应试剂能够降低制备成本，并通过提高产量而能够用于大量生产。

Methods of treating protozoal infections

FIELD: medicine.SUBSTANCE: group of inventions refers to treatment or prevention of protozoal infection in a subject. That is ensured by using a compound or its pharmaceutically acceptable salt selected from: NCL015, NCL016, NCL017, NCL020, NCL021, NCL022, NCL023, NCL024, NCL025, NCL026, NCL027, NCL028, NCL029, NCL030, NCL031, NCL032, NCL033, NCL034, NCL035, NCL036, NCL037, NCL038, NCL039, NCL040, NCL041, NCL042, NCL043, NCL044, NCL045, NCL046, NCL052, NCL053, NCL054, NCL062, NCL072, NCL073, NCL074, NCL075, NCL076, NCL077, NCL078, NCL079, NCL080, NCL081, NCL082, NCL083, NCL084, NCL085, NCL086, NCL087, NCL088, NCL089, NCL093, NCL094, NCL096, NCL097, NCL099, NCL100, NCL101, NCL102, NCL103, NCL107, NCL108, NCL109, NCL110, NCL112, NCL113, NCL114, NCL115, NCL116, NCL117, NCL118, NCL119, NCL120, NCL121, NCL123, NCL125, NCL126, NCL127, NCL129, NCL130, NCL131, NCL132, NCL133, NCL134, NCL135, NCL136, NCL137, NCL138, NCL139, NCL140, NCL141, NCL143, NCL144, NCL145, NCL146, NCL147, NCL150, NCL151, NCL152, NCL153, NCL154, NCL155, NCL156, NCL160, NCL164, NCL165, NCL166, NCL170, NCL171, NCL172, NCL174, NCL175, NCL176, NCL177, NCL188, NCL190, NCL191, NCL215, NCL216, NCL217, NCL219, NCL224, NCL225, NCL226, NCL228, NCL229, NCL231, NCL232, NCL233, NCL234, NCL235, NCL236, NCL237, NCL248, NCL249, NCL254, NCL257, NCL259, NCL261, NCL263, NCL265, NCL266, NCL271, NCL272, NCL273, NCL274. Group of inventions relates to use of a compound or a pharmaceutically acceptable salt, to an antiprotozoal pharmaceutical composition containing a compound, as well as to a medical device containing the composition.EFFECT: invention provides extending the range of products for treating or preventing protozoal infection in a subject.19 cl, 13 dwg, 9 tbl, 14 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК A61K 31/155 (2006.01) A61K 31/17 (2006.01) A61K 31/4045 (2006.01) A61K 31/4192 (2006.01) A61K 31/341 (2006.01) A61K 31/498 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА A61K 31/44 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ ...

Synthesis of aliskiren

The present invention provides novel process for the preparation of renin inhibitor Aliskiren or its derivatives, and its pharmaceutically acceptable salts. The present invention also provides novel intermediates used in the preparation of Aliskiren.

Protein inhibitor and application thereof

一类Legumain蛋白抑制剂及其应用，其结构式为 该抑制剂能够特异性抑制肿瘤细胞中高表达的Legumain蛋白，通过与Legumain蛋白的结合域结合，抑制其活性并降低蛋白表达，从而抑制肿瘤细胞的迁移和侵袭，并诱导降低肿瘤细胞对化疗的耐受能力，具有特异性好，生物利用度高，无肝肾毒副作用等特点，可用于治疗乳腺癌，其作用机制明确，能有效抑制肿瘤的转移和侵袭。

Method for producing organic nitro compounds

FIELD: chemistry. SUBSTANCE: invention relates to the organic nitro compound chemistry and specifically to a process for producing nitro compounds of the general formula of RNO 2 , where R=n-C 4 H 9 O-; O 2 NO(CH 2 ) 2 O-; O 2 NO(CH 2 ) 2 O(CH 2 ) 2 O-; O 2 NOCH 2 CH(ONO 2 )CH 2 O-; (O 2 NOCH 2 ) 3 CCH 2 O-; where m=1, 2; where n=2, 3; , which can find application in producing high-energy products, medicines, dyes, polymers, etc. The method consists in the fact that the corresponding alcohols or amines derivatives are subject to nitration with nitric oxide (V) or its mixture with 100% nitric acid in a medium of lower hydrofluorocarbons, the process is carried out at a pressure of 3-60 bar and a temperature of 5-40°C at a molar ratio of the corresponding starter compound and nitrating agent 1:(1.1-4.4). EFFECT: method allows to reduce fire and explosion hazard of the process, improve its environmental performance and obtain the desired compounds with high output. 2 cl, 20 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ФОРМУЛА (21)(22) Заявка: (19) RU (51) МПК C07C 201/02 C07C 203/04 C07C 241/00 C07C 243/02 C07D 233/02 C07D 239/04 C07D 493/04 2016112861, 05.04.2016 05.04.2016 Дата регистрации: C1 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (72) Автор(ы): Жарков Михаил Николаевич (RU), Кучуров Илья Григорьевич (RU), Фоменков Игорь Владимирович (RU), Злотин Сергей Григорьевич (RU) (73) Патентообладатель(и): Федеральное государственное бюджетное учреждение науки Институт органической химии им. Н.Д. Зелинского Российской академии наук (ИОХ РАН) (RU) Приоритет(ы): (22) Дата подачи заявки: 05.04.2016 (45) Опубликовано: 17.02.2017 Бюл. № 5 (56) Список документов, цитированных в отчете о поиске: I.V. KUCHUROV ET AL., Synthesis of nitric acid esters from alcohols in a dinitrogen pentoxide/carbon dioxide liquid system, MENDELEEV COMMUN., 2012, 22, pp.67-69. I.V. KUCHUROV ET AL., Nitration of carbonic, sulfuric and ...

A kind of method for preparing diazoparaffins

本发明涉及形成重氮烷的方法。本发明的一个方面提供了用于由起始材料制备N‑烷基‑N‑亚硝基化合物的方法，所述方法包括使用三元酸对胺进行酸化。本发明的第二方面提供了用于制备重氮烷的方法，所述方法包括使N‑烷基‑N‑亚硝基化合物与碱和相转移催化剂反应，其中没有使用有机溶剂。

Chiral diacyl-hydrazine ligands for modulating expression of exogenic genes by means of ecdysone-receptor complex

FIELD: chemistry. SUBSTANCE: invention relates to compounds of general formula III and their pharmaceutically acceptable salts, A represents (C 1 -C 6 )alkyl-O-, phenyl-(C 1 -C 6 )alkyl-O-; aryl, selected from phenyl, naphthyl, and which is possibly substituted by 1-3 substituents, given in the invention formula; or heteroaryl, which has four or five carbon atoms and one heteroatom, selected from oxygen, nitrogen and sulphur, which is possibly substituted by 1-3 substituents, given in the invention formula; B represents phenyl, possibly substituted by 1-3 substituents, where substituents are selected from (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (C 1 -C 6 )alkyl-O-, hydroxy, amino and halogeno; and R 1 and R 2 independently represent (C 1 -C 6 )alkyl, phenyl-(C 1 -C 6 )alkyl-, hydroxy-(C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (C 2 -C 6 )alkenyl or (C 2 -C 6 )alkynyl; on condition that R 1 is different from R 2 ; where absolute configuration of asymmetric R 1 and R 2 -carrying carbon atom is mainly R-configuration. Invention also relates to pharmaceutical composition, possessing ability to modulate gene expression, methods of modulation of gene expression in host cell, method of regulating expression of endogenous or heterologous gene in transgenic subject, method of regulating transgenic expression in transgenic subject, method of polypeptide production and to method of obtaining formula IV compound. Method includes stages: a) interaction of formula V compound with formula IV compound with obtaining formula VII compound; b) reduction of formula VII compound with obtaining formula VIII compound, b) interaction of formula VIII compound with formula B-CO-LG compound, where B has values, given above, and LG is leaving group representing -F, -Cl or -Br, with formation of formula IX compound, d) removal of group R 7 CO 2 - from formula IX compound with obtaining formula X compound, e) interaction of formula X compound with formula A-CO-LG compound, where A has values, ...