СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ МУТИЛИНА ИЛИ ИХ СОЛЕЙ С КИСЛОТАМИ

Compounds of formula I <CHEM> wherein R1 and R2 are the same or different and each represent hydrogen, alkyl, alkenyl, cycloalkyl, aryl or aralkyl are produced by a new environmentally acceptable process.

Azabicyclic carbamoyloxy mutilin derivatives for antibacterial use.

Compounds of formula (3), and pharmaceutically acceptable salts and derivatives thereof: in which: R.1 is vinyl or ethyl; and R2 is a group R3, R4CH2~, or R5R6C=CH-; wherein each of R3 and R4 is an azabicyclic ring system or R5 and R^ together with the carbon atom to which they are attached form an azabicyclic ring system, are useful in the prevention and treatment of microbial infections.

Carbamoyloxy derivatives of mutiline and their use as antibacterials.

Derivatives of mutiline of formula (1a)and pharmaceutically acceptable salts and derivatives thereof, in which r1 is ethyl or vinyl, y is a carbamoyloxy group, which the n-atom is unsubstituted, or mono- or di-substituted, are useful in the treatment of bacterial infections.

Novel compounds

Novel compounds.

Compounds of formula (1a)and pharmaceutically acceptable salts and derivativews thereof in which y is a carbamoyloxy group, in which the n-atom is unsubstituted, or mono- or di-substituted, are useful in the treatment of bacterial infections.

Carbamoyloxy derivatives of mutiline and their useas antibacterials.

Derivatives of mutiline of formula (1A) and pharmaceutically acceptable salts and derivatives thereof, in which R<1> is ethyl or vinyl, Y is a carbamoyloxy group, in which the N-atom is unsubstituted, or mono- or di-substituted, are useful in the treatment of bacterial infections.

Carb moylo y der vativ s of utiline and their use as antibacterials

Novel compounds

Novel compounds

NEUE PLEUROMUTILINDERIVATE, IHRE VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG

PCT No. PCT/EP93/01033 Sec. 371 Date Jan. 3, 1994 Sec. 102(e) Date Jan. 3, 1994 PCT Filed Apr. 29, 1993 PCT Pub. No. WO93/22288 PCT Pub. Date Nov. 11, 1993 (I) A compound of formula (I), in which each of R1 and R2 is independently hydrogen, alkyi or, together with the carbon atom to which it is bonded, a cycloalkyl; and each of R3 and R4 is independently hydrogen, alkyl or substituted alkyl. The compounds are useful intermediates and prodrugs.

Novel thiazolidine, process for the preparation of thiazolidines and their use

... 2-Isopropyl-5,5-dimethylthiazolidine and process for its preparation by reduction of the compound III and its use for the preparation of the compound of the formula II. ...

MUTILINDERIVATE AND YOUR USE AS DRUGS

NEW THIAZOLIDIN, PROCEDURES FOR THE PRODUCTION OF THIAZOLIDINEN AND YOUR USE

NEW PLEUROMUTILINDERIVATE

PLEUROMUTILIN DERIVATIVES

Carbamoyloxy derivatives of mutiline and their use as antibacterials

Novel pleuromutilin derivatives

PLEUROMUTILIN COMPLEXES

PLEUROMUTILIN COMPLEXES Complexes and pharmaceutical preparations containing complexes of the pleuromutilin derivative of formula I in free base or in acid addition or quaternary salt form and cyclodextrin are described. They can be prepared by complexing the above pleuromutilin compound with an appropriate cyclodextrin. They are indicated for use as pharmaceuticals, e.g. as antibiotics, especially in veterinary medicine, e.g. as feed additives.

KARBAMOILOKSIPROIZVODNYE MUTILIN AND THEIR USE AS ANTIBACTERIAL AGENTS

NEW DERIVED AND ITS APPLICATION

METHOD OF PRODUCING PLEUROMUTILINOV

DERIVED AND THEIR APPLICATION AS THE PHARMACEUTICAL PREPARATIONS

Mutilin derivatives and their use as pharmaceutical

... 14-0-[(((C1.6)Alkoxy-(C1.6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[(((C1-6)Mono- or dialkylamino-(C1.6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Hydroxy-(C1-6)-alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Formyl-(C0.5)-alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Guanidino-imino-(C1-6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Ureido-imino-(C1-6)alky)-phenylsulfany)-acety)-mutilins, 14-O-[((Thioureido-imino-(C1-6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((lsothioureido-imino-(C1-6)alkyl)-phenylsulfanyl)-acetyl]-mutilins and their use as pharmaceuticals.

PLEUROMUTILIN DERIVATIVES

12-EPI-PLEUROMUTILINS

СОЛИ ВАЛНЕМУЛИНА И ОРГАНИЧЕСКИХ КИСЛОТ

FIELD: chemistry. SUBSTANCE: invention relates to salts of valnemulin compounds of formula I and organic acids selected from a group which includes D-tartaric acid and fumaric acid, (I). The invention also relates to method for synthesis of said salts and to their use as a medicinal agent for treating bacterial infections in warm-blooded animals. EFFECT: obtaining novel salts of valnemulin which are characterised by high degree of crystallinity and high degree of purification, manufacturability and high stability during storage. 14 cl, 1 tbl, 3 ex

КОМПЛЕКС ПРОИЗВОДНОГО ПЛЕВРОМУТИЛИНА, СПОСОБ ЕГО ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ЕГО СОДЕРЖАЩАЯ

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention describes complexes and pharmaceutical preparations containing complexes of pleuromutilin derivative of the formula (I) given in description as free base or salt obtaining by addition of acid and cyclodextrin. They can be prepared by chelating the above indicated compound pleuromutilin with suitable cyclodextrin. They can be used as pharmaceutical preparations, for example, antibiotics, in part, in veterinary science as food additions. EFFECT: improved method of preparing. 13 cl, 4 tbl ус; 660с ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (51) МПК ВИ” 2 099 324 ' С 07 С 323/26, А 61 К 31/255 13) СЛ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 5052221/04, 23.01.1992 (30) Приоритет: 24.07.1991 АТ А 1477/91 (46) Дата публикации: 20.12.1997 (56) Ссылки: Ц, патент, 4675330, кл. А 01 М 3106, 1987. (71) Заявитель: Биохеми ГмбХ (АТ) (72) Изобретатель: Хайнрих Франц Матоус[АТ], Эрих Цайсль[АТ] (73) Патентообладатель: Биохеми ГмбХ (АТ) (54) КОМПЛЕКС ПРОИЗВОДНОГО ПЛЕВРОМУТИЛИНА, СПОСОБ ЕГО ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ЕГО СОДЕРЖАЩАЯ (57) Реферат: Предлагаются комплексы и фармацевтические препараты, содержащие комплексы производного плевромутилина формулы |, указанной в описании, в форме свободного основания или соли, получаемой добавлением кислоты, и циклодекстрина. Они могут быть получены — комплексованием вышеназванного соединения плевромутилина с подходящим цикподекстрином. Они показаны для применения в качестве фармацевтических препаратов, например в качестве антибиотиков, особенно В ветеринарии, например в качестве пищевых добавок. 3 с. и 10 з.п.ф-лы, 4 табл. 2099324 С1 КО ус; 660с ПЧ Го КУЗЗАМ АСЕМСУ ГОК РАТЕМТ$ АМО ТКАОЕМАКК$ 13) ВУ” 2 099 324 '” С1 о С 07С 323/26, А 61 К 31/255 12) АВЗТКАСТ ОЕ 1МУЕМТОМ (21), (22) АррИсаНоп: 5052221104, 23.01.1992 (30) Рпогу: 24.07.1991 АТ А 1477/91 (46) Рае о! рибИсаНоп: 20.12.1997 (71) АррИсапе: Воквет! СтЬКК (АТ) (72) ...

PLEUROMUTILIN DERIVATIVES

... 1303038 Pleuromutilin derivatives BIOCHEMIE GmbH 1 July 1970 [2 July 1969] 32020/70 Heading C2A Novel pleuromutilin derivatives having the general Formula I wherein R is or hydrogen, are prepared by (a) cultivating Clitopilus passeckerianns (Pil.) Sing. NRRL 3100 or NRRL 3279, Clitopilus prunulus (Scop. ex Fr.) Kummner NRRL 3473, Clitopilus pinsitus (Fr.) ss. Romagn. Joss. NRRL 3474, or a, compound of Formula I-producing mutant or variant of one of these micro-organisms, under aerobic conditions in an aqueous nutrient medium containing assimilable sources of nitrogen and carbon and isolating the resulting compounds of Formula I; or (b) when R is hydrogen in Formula I, enzymatically acetylating mutilin of Formula II with one of the aforesaid micro-organisms or the dry mycelium or an enzyme extract thereof and isolating the resulting mutilin 14-acetate. Process (a) is preferably performed in the presence of a source of the fatty acid R groups, e.g. maize oil, sunflower oil, olive oil, or ...

NEUE PLEUROMUTILINDERIVATE, IHRE VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG

NEW PLEUROMUTILIN DERIVATIVES

PLEUROMUTILINDERIVATE WITH ANTIMICROBIAL EFFECT

PHARMAZEUTISCHE PLEUROMUTILIN-ZUBEREITUNG

Valnemulin salts with organic acids

Pleuromutilin derivatives with antimicrobial activity

PLEUROMUTILINS

Compounds of formula I (see formula I) wherein R1 and R2 are the same or different and each represent hydrogen, alkyl, alkenyl, cycloalkyl, aryl or aralkyl are pro-duced by a new environmentally acceptable process.

AZABICYCLIC CARBAMOYLOXY MUTILIN DERIVATIVES FOR ANTIBACTERIAL USE

Compounds of formula (3), and pharmaceutically acceptable salts and derivatives thereof, in which R1 is vinyl or ethyl; and R2 is a group R3, R4CH2-, or R5R6C=CH-; wherein each of R3 and R4 is an azabicyclic ring system or R5 and R6 together with the carbon atom to which they are attached form an azabicyclic ring system, are useful in the prevention and treatment of microbial infections.

Process for the preparation of pleuromutilins

PLEUROMUTILIN DERIVATIVES

Process for the preparation of a pleuromutilin derivative and its acid addition salts

The invention relates to a novel process for the preparation of the pleuromutilin derivative I and its acid addition salts which is easy to implement industrially and is environmentally friendly. Pleuromutilin is initially converted via the tosylate into the pleuromutilin cysteamine which is reacted with an appropriate valine derivative, and the target compound is then liberated therefrom. ...

PLEUROMOTULINE COMPLEXES

NEW PLEUROMUTILINDERIVATE, YOUR USE AND PROCEDURE FOR YOUR PRODUCTION

AZABICYCLIACHE CARBAMOYLOXY MUTILIN OF DERIVATIVES AS ANTIBACTERIAL MEANS

Procedure for the production of new Pleuromutilin derivatives

PHARMACEUTICAL PLEUROMUTILIN PREPARATION

PROCEDURE FOR THE PRODUCTION OF A PLEUROMUTILINDERIVATS AND ITS ACID ADDITION SALTS

CRYSTALLINE VALNEMULINSALZE WITH ORGANIC ACIDS

VERFAHREN ZUR HERSTELLUNG EINES PLEUROMUTILINDERIVATS UND SEINER SAEUREADDITIONSSALZE

MUTILIN DERIVATIVES AND THEIR USE AS PHARMACEUTICAL

... 14-0-[(((C1.6)Alkoxy-(C1.6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O- [(((C1-6)Mono- or dialkylamino-(C1.6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Hydroxy-(C1-6)-alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Formyl- (C0.5)-alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Guanidino-imino-(C1- 6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Ureido-imino-(C1-6)alky)- phenylsulfany]-acety]-mutilins, 14-O-[((Thioureido-imino-(C1-6)alkyl)- phenylsulfanyl)-acetyl]-mutilins, 14-O-[((lsothioureido-imino-(C1-6)alkyl)- phenylsulfanyl)-acetyl]-mutilins and their use as pharmaceuticals.

PLEUROMUTILINS

... - 26 - 970-9786 PLEUROMUTILINS Compounds of formula I I wherein R1 and R2 are the same or different and each represent hydrogen, alkyl, alkenyl, cycloalkyl, aryl or aralkyl are produced by a new environmentally acceptable process. 6300/IG/RT 13-September-1990 ...

Patent TW307770B

PHARMAZEUTISCHE PLEUROMUTILIN-ZUBEREITUNG

PLEUROMUTILINE.

CARNAMOYLOXY DERIVATIVES OF MUTILIN AND THEIR USE AS ANTIBACTERIAL OF MEANS

NEUES THIAZOLIDIN, VERFAHREN ZUR HERSTELLUNG VON THIAZOLIDINEN UND IHRE VERWENDUNG

Azabicyclic carbamoyloxy mutilin derivatives for antibacterial use

PLEUROMUTILIN DERIVATIVES FROM CLITOPILUS SPECIES

MUTILIN DERIVATIVES AND THEIR USE AS PHARMACEUTICAL

... 14-0-[(((C1.6)Alkoxy-(C1.6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[(((C1-6)Mono- or dialkylamino-(C1.6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Hydroxy-(C1-6)-alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Formyl-(C0.5)-alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Guanidino-imino-(C1-6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Ureido-imino-(C1-6)alky)-phenylsulfany]-acety]-mutilins, 14-O-[((Thioureido-imino-(C1-6)alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((lsothioureido-imino-(C1-6)alkyl)-phenylsulfanyl)-acetyl]-mutilins and their use as pharmaceuticals.

PLEUROMUTILIN COMPLEXES

PLEUROMUTILIN COMPLEXES Complexes and pharmaceutical preparations containing complexes of the pleuromutilin derivative of formula I in free base or in acid addition or quaternary salt form and cyclodextrin are described. They can be prepared by complexing the above pleuromutilin compound with an appropriate cyclodextrin. They are indicated for use as pharmaceuticals, e.g. as antibiotics, especially in veterinary medicine, e.g. as feed additives.

СОЛИ ВАЛНЕМУЛИНА И ОРГАНИЧЕСКИХ КИСЛОТ

... 1. Соли валнемулина формулы I и органических кислот. 2. Соли по п.1, отличающиеся тем, что органические кислоты выбирают из группы, включающей монокарбоновые кислоты, дикарбоновые кислоты и трикарбоновые кислоты. 3. Соли по п.1, отличающиеся тем, что органические кислоты выбирают из группы, включающей муравьиную кислоту, уксусную кислоту, пропионовую кислоту, аскорбиновую кислоту, гликолевую кислоту, молочную кислоту, пировиноградную кислоту, миндальную кислоту, щавелевую кислоту, малоновую кислоту, янтарную кислоту, аспарагиновую кислоту, глутаминовую кислоту, глутаровую кислоту, адипиновую кислоту, пимелиновую кислоту, субериновую кислоту, малеиновую кислоту, фумаровую кислоту, фталевую кислоту, изофталевую кислоту, терефталевую кислоту, яблочную кислоту, винную кислоту и лимонную кислоту. 4. Соли по п.1, отличающиеся тем, что органические кислоты выбирают из группы, включающей энантиомерно чистые моно- и дикарбоновые кислоты. 5. Соли по п.1, отличающиеся тем, что органические кислоты ...

CARNAMOYLOXY DERIVATE VON MUTILIN UND DEREN VERWENDUNG ALS ANTIBAKTERIELLES MITTELS

Pleuromotuline Komplexe

Pleuromutilin beta-ketoesters

New pleuromutilin derivative and its use

12-EPI-PLEUROMUTILINS

A compound selected from 14-O-[((Alkyl-, cycloalkyl-, heterocycloalkyl-, heteoroaryl-, or aryl)-sulfanyl)-acetyl]-12-epi-mutilins, or 14-0-[((Alkyl-, cycloalkyl-, heterocycloalkyl-, heteoroaryl-, or aryl)-oxy)-acetyl]-12-epi-mutilins, wherein 12-epi-mutilin is characterized in that the mutilin ring at position 12 is substituted by two substituents, the first substituent at position 12 of the mutilin ring is a methyl group which methyl group has the inverse stereochemistry compared with the stereochemistry of the methyl group at position 12 of the naturally occurring pleuromutilin ring, the second substituent at position 12 of the mutilin ring is a hydrocarbon group comprising at least one nitrogen atom and all other substituents of the mutilin ring having the same stereochemistry compared with the stereochemistry of the substituents at the corresponding positions in the naturally occurring pleuromutilin ring; optionally in the form of a salt and/or solvate, wherein the naturally occurring ...

Pleuromutilin derivatives and their use as antimicrobials.

A compound of formula (I) or of formula (II) wherein X is oxygen or sulfur, and Y is a residue of pipecolic acid or a residue of an amino acid, preferably a naturally occurring amino acid.

PHENYL AMINO ACID PLEUROMUTILIN DERIVATIVES AND USE THEREOF AS ANTIBIOTICS

A compound of formula (l) (see formula I) or of formula (II) (see formula II) wherein X is oxygen or sulfur, and Y is a residue of pipecolic acid or a residue of an amino acid, preferably a naturally occurring amino acid. The compounds of the present invention are suitable for use as an antibiotic.

Pleuromutilin derivatives

Pleuromutiline.

CRYSTALLINE, ENANTIOMERICALLY PURE PLEUROMUTILINS AND PROCESSES FOR THE PREPARATION THEREOF

Process for the preparation of a Compound of formula I in the form of a single stereoisomer in crystalline form, comprising deprotecting the amine group in a Compound of formula IIa or in a mixture of a compound of formula IIa With a compound of formula IIb and isolating a Compound of formula I from the reaction mixture; Compounds and salts of Compounds of formula I in crystalline form; pharmaceutical compositions comprising such salts; processes for the preparation of intermediates and intermediates in a process for the preparation of a Compound of formula I.

Pleuromutilin derivatives and their use as antimicrobials

式(I)或式(II)的化合物，其中，X为氧或硫，和Y为哌可酸残基或氨基酸残基，优选天然存在的氨基酸。

derivados de pleuromutilina, seu uso e composição farmacêutica

Novel compounds

Novel compounds

Organic compounds

PROCESS FOR THE PRODUCTION OF PLEUROMUTILIN DERIVATIVES

Process for the preparation of pleuromutilins

Process for the preparation of a Compound of formula I in the form of a single stereoisomer in crystalline form, comprising deprotecting the amine group in a Compound of formula IIa or in a mixture of a compound of formula IIa With a compound of formula IIb and isolating a Compound of formula I from the reaction mixture; Compounds and salts of Compounds of formula I in crystalline form; pharmaceutical compositions comprising such salts; processes for the preparation of intermediates and intermediates in a process for the preparation of a Compound of formula I.

PLEUROMUTILIN DERIVATIVES FROM CLITOPILUS SPECIES

CARBAMOYLOXY DERIVATIVES OF MUTILINE AND THEIR USE AS ANTIBACTERIALS

Derivatives of mutiline of formula (1A) and pharmaceutically acceptable salts and derivatives thereof, in which R1 is ethyl or vinyl, Y is a carbamoyloxy group, in which the N-atom is unsubstituted, or mono- or di-substituted, are useful in the treatment of bacterial infections.

Process for preparing pleuromutilin

VALNEMULIN SALTS WITH ORGANIC ACIDS

12-epi-플루로뮤틸린

... 14-O-[((알킬-, 사이클로알킬-, 헤테로사이클로알킬-, 헤테로아릴- 또는 아릴)-설파닐)-아세틸]-12-epi-뮤틸린 또는 14-O-[((알킬-, 사이클로알킬-, 헤테로사이클로알킬-, 헤테로아릴- 또는 아릴)-옥시)-아세틸]-12-epi-뮤틸린으로부터 선택되며, 12-epi-뮤틸린이, 뮤틸린 고리가 12번 위치에서 2개의 치환기로 치환되고, 뮤틸린 고리의 12번 위치에서 제1 치환기가 천연 플루로뮤틸린 고리의 12번 위치의 메틸 기의 입체화학 구조와는 반대되는 입체화학 구조를 가지는 메틸 기이고, 뮤틸린 고리의 12번 위치에서 제2 치환기가 하나 이상의 질소 원자를 포함하는 탄화수소 기이고, 뮤틸린 고리의 다른 치환기들은 모두 천연 플루로뮤틸린 고리에서 대응되는 위치에 존재하는 치환기들의 입체화학 구조와 동일한 입체화학 구조를 가지는 것을 특징으로 하며, 천연 플루로뮤틸린이 하기 식으로 표시되는; 선택적으로 염 및/또는 용매화물 형태인, 화합물, 이 화합물의 제조 방법, 및 약제로서의 용도.

Improvements in or relating to organic compounds

The present invention provides a process for the production of compounds of formula I, <IMAGE> in which n is 2, 3, 4 or 5 R1 is ethyl or vinyl, and either R2 and R3 are the same or different and each signifies alkyl of 1 to 4 carbon atoms, or R2 and R3, together with the nitrogen atom to which they are attached, form a heterocyclic ring optionally containing a second hetero moiety selected from oxygen, sulphur or =N-R5, in which R5 is alkyl of 1 to 4 carbon atoms, or an acid addition salt form thereof, comprising reacting a compound of formula II, <IMAGE> in which R1 is as defined above, and R6 is alkyl of 1 to 4 carbon atoms or phenyl, unsubstituted or substituted by alkyl of 1 to 4 carbon atoms, with a compound of formula III, <IMAGE> in which n, R2 and R3 are as defined above, characterised in that the reaction is effected in the presence of a phase transfer catalyst, and, where required, converting a resulting free base form of the compounds of formula I into an acid addition salt form, or vice versa. The compounds of formula I are indicated for use as antibiotics having an antibacterial effect and are also indicated for use as prophylactic additives for animal feeding stuffs and animal drinking water.

Novel compounds

CARBAMOYLOXY DERIVATIVES OF MUTILIN AND THEIR USE AS BACTERICIDES

The compounds are useful for the treatment of bacterialinfections. The mutilin derivatives have the formulawhere R1 is ethyl or vinyl, Y is carbamoyloxygroup where theN-atom is not substituted or is mono- or disubstituted. Theinvention also relates to their pharmaceutically acceptable saltsand derivatives.9 claims ...

PLEUROMUTILIN COMPLEXES

MUTILIN DERIVATIVES - VETERINARY AGENTS

PLEUROMUTILIN DERIVATIVES

A compound of formula (I), in which each of R1 and R2 is independently hydrogen, alkyl or, together with the carbon atom to which it is bonded, a cycloalkyl; and each of R3 and R4 is independently hydrogen, alkyl or substituted alkyl. The compounds are useful intermediates and prodrugs.

PLEUROMUTILIN DERIVATIVES

A compound of formula (I), in which each of R1 and R2 is independently hydrogen, alkyl or, together with the carbon atom to which it is bonded, a cycloalkyl; and each of R3 and R4 is independently hydrogen, alkyl or substituted alkyl. The compounds are useful intermediates and prodrugs.

NEW PLEUROMUTILIN DERIVATIVE AND ITS USE

The invention is directed to the L-tartrate salt of trans-3-aminocyclobutyl (lS,2R,3S,4S:,6R,7R,8R-,14R)-4-ethenyl-3-hydroxy-2,4,7, 14-tetramethyl-9- oxotricyclo[5.4.3.01,8]tetradec-6-yl imidodicarbonate (Compound IA.) Compound IA is useful for the treatment of a variety of diseases and conditions, such as respiratory tract and skin and skin structure infections. Accordingly, the invention is further directed to pharmaceutical compositions comprising Compound IA. The invention is still further directed to methods of treating respiratory tract and skin and skin structure infections using Compound IA or a pharmaceutical composition comprising Compound IA.

PROCESS FOR THE PREPARATION OF PLEUROMUTILINS

Process for the preparation of a Compound of formula I in the form of a single stereoisomer in crystalline form, comprising deprotecting the amine group in a Compound of formula IIa or in a mixture of a compound of formula IIa With a compound of formula IIb and isolating a Compound of formula I from the reaction mixture; Compounds and salts of Compounds of formula I in crystalline form; pharmaceutical compositions comprising such salts; processes for the preparation of intermediates and intermediates in a process for the preparation of a Compound of formula I.

PROCESS FOR THE PREPARATION OF PLEUROMUTILINS

Process for the preparation of a Compound of formula I in the form of a single stereoisomer in crystalline form, comprising deprotecting the amine group in a Compound of formula IIa or in a mixture of a compound of formula IIa With a compound of formula IIb and isolating a Compound of formula I from the reaction mixture; Compounds and salts of Compounds of formula I in crystalline form; pharmaceutical compositions comprising such salts; processes for the preparation of intermediates and intermediates in a process for the preparation of a Compound of formula I.

NEUE PLEUROMUTILINDERIVATE

Pleuromutilin complexes

FORFARANDE FOR FRAMSTELLNING AV 14-DESOXI-14-ACETOXIMUTILIN

PLEUROMUTILIN-DERIVATE

MUTILINDERIVATE UND IHRE VERWENDUNG ALS ARZNEIMITTEL

Novel compounds

Valnemulin salts with organic acids

DERIVATIVES OF PLEUROMUTILINA AND ITS USE AS ANTIMICROBIALSES

Process For Preparing Pleuromutilin

The present disclosure provides processes for preparing (+)-pleuromutilin and synthetic (+)-pleuromutilin produced therefrom. Also provided are intermediates prepared thereby and processes for preparing these intermediates. 2. The process of claim 1 , wherein the organic solvent is a polar organic solvent.3. The process of claim 1 , wherein the organic solvent is an ethereal solvent.4. The process of claim 1 , wherein the organic solvent is tetrahydrofuran.5. The process of claim 1 , wherein the conditions are anaerobic.6. The process of claim 1 , wherein the organic solvent further comprises water.7. The process of claim 1 , comprising about 2.5 to about 3.5 moles of samarium(II) iodide per 1 mole of the compound of Formula I.8. The process of claim 1 , wherein the oxygen protecting group is methoxymethyl claim 1 , tetrahydropyranyl claim 1 , t-butyl claim 1 , allyl claim 1 , benzyl claim 1 , silyl claim 1 , acetyl claim 1 , pivaloyl claim 1 , trityl claim 1 , or benzoyl.9. The process of claim 1 , wherein the oxygen protecting group is methoxymethyl ether.11. The process of claim 10 , wherein Ris triphenyl methyl.12. The process of claim 10 , wherein the conditions effective to produce the compound of Formula IB comprise formic acid.13. The process of claim 10 , wherein the oxidizing conditions comprise a copper catalyst.14. The process of claim 13 , wherein the copper catalyst is [Cu(MeCN)]OTf or CuCu(OTf).16. The process of claim 15 , wherein the contacting is performed in an organic solvent under conditions sufficient to produce the compound of Formula III.17. The process of claim 16 , wherein the organic solvent is toluene.18. The process of claim 16 , wherein the temperature is about −10 to about 10° C.19. The process of claim 15 , wherein the diastereomeric excess of the compound of Formula III is at least 20%.22. The process of claim 21 , wherein the conditions sufficient to provide the compound of Formula VI comprise tris(2 claim 21 ,2 claim 21 ,6 claim 21 ...

PLEUROMUTILIN DERIVATIVE HAVING 2-AMINO PHENYL MERCAPTAN SIDE CHAIN AS WELL AS PREPARATION METHOD AND APPLICATION THEREOF

A pleuromutilin derivative having a 2-amino phenyl mercaptan side chain as well as a preparation method and application thereof are provided. The derivative has a structure represented by formula 2 or formula 3, wherein, R1, R2 and R3 are each independently selected from a hydrogen atom, hydroxyl, amino, sulfydryl, hydroxymethyl, amine methyl, nitro, halogen, trihalogenated methyl, methyl, natural amino acid acylamino and C1-6 alkoxy. The plueuromutilin derivative in the disclosure has good activity of inhibiting drug-resistant and , and is especially suitable for preventing and treating infectious diseases caused by human or animal or drug-resistant or multidrug resistant bacteria as a novel antibacterial drug. 2. The pleuromutilin derivative according to claim 1 , wherein claim 1 , Ris one of hydrogen atom claim 1 , hydroxyl claim 1 , amino claim 1 , hydroxymethyl claim 1 , amine methyl claim 1 , fluorine claim 1 , trifuoromethyl claim 1 , nitro claim 1 , trifluoromethyl claim 1 , methoxy claim 1 , ethoxyl claim 1 , prolyl amino and valyl amino;{'sub': '2', 'Ris one of hydrogen atom, hydroxyl, amino, hydroxymethyl, amine methyl, fluorine, trifiuoromethyl, nitro, trifluoromethyl, methoxy, ethoxyl, prolyl amino and valyl amino; and'}{'sub': '3', 'Ris one of hydrogen atom, hydroxyl, amino, hydroxymethyl, amine methyl, fluorine, trifuoromethyl, nitro, trifluoromethyl, methoxy, ethoxyl, prolyl amino and valyl amino.'}3. The pleuromutilin derivative according to claim 1 , wherein claim 1 ,{'sub': 1', '2', '3, 'Ris methyl, Ris a hydrogen atom, and Ris a hydrogen atom;'}{'sub': 1', '2', '3, 'or Ris a hydrogen atom, Ris methyl, and Ris a hydrogen atom;'}{'sub': 1', '2', '3, 'or Ris a hydrogen atom, Ris a hydrogen atom, and Ris methyl;'}{'sub': 1', '2', '3, 'or Ris a fluorine atom, Ris a hydrogen atom, and Ris a hydrogen atom;'}{'sub': 1', '2', '3, 'or Ris a hydrogen atom, Ris a fluorine atom, and Ris a hydrogen atom;'}{'sub': 1', '2', '3, 'or Ris a hydrogen atom, Ris a ...

Small molecules active against gram-negative bacteria

Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

Process for the preparation of pleuromutilins

Pleuromuthyline complexes

Process for the preparation of pleuromutilins

본 발명은, 식 IIa의 화합물 또는 식 IIa의 화합물과 식 IIb의 화합물의 혼합물에서 아민기를 탈보호하고, 반응 혼합물로부터 식 I의 화합물을 분리하는 단계를 포함하는, 식 I의 화합물을 단일한 입체이성질체의 결정 형태로 제조하는 방법; 결정형의 식 I의 화합물 및 화합물의 염; 상기 염을 포함하는 약학 조성물; 식 I의 화합물을 제조하는 공정의 중간산물의 제조 방법과 중간산물을 제공한다.

Pleuromutilin complexes

介绍了由以游离碱、酸加成盐或季胺盐型的式I 的截短侧耳素衍生物和环糊精形成的一些络合物和 含此络合物的药物制剂。该络合物可以用络合上述 截短侧耳素和一种适当的环糊精的方法制备，据证明 可以作为药物(如抗生素)，尤其是作为兽药使用，如 以饲料添加剂形式使用。

Lefamulin intermediate compound and application thereof in preparation of Lefamulin

本发明公开了一种Lefamulin的中间体化合物及其在Lefamulin制备中的应用，以期解决现有技术中Lefamulin制备成本高、收率低的技术问题。本发明提供一种中间体化合物 及其制备方法，并将上述中间体化合物在制备Lefamulin或Lefamulin相关的医药中间体中的应用。本发明克服了现有技术的生产过程中碰到的手性氧化缺乏手性诱导，造成目标化合物转化率非常低、成本非常高、工业化生产困难的缺陷；工业化应用时能够有效降低生产成本，且可以有效控制三废的产生，具有显著的经济效益和社会效益。

Pleuromutilin compounds for treating bacterial infectious diseases

本发明涉及新型截短侧耳素类化合物、它们的药物组合物及使用方法。此外，本发明还涉及用于治疗细菌感染的治疗方法，包括耐药性微生物造成的感染，包括多重耐药性微生物。

New process for producting pleuromutilin derivatives

Process for the preparation of pleuromutilins

본 발명은, 식 IIa의 화합물 또는 식 IIa의 화합물과 식 IIb의 화합물의 혼합물에서 아민기를 탈보호하고, 반응 혼합물로부터 식 I의 화합물을 분리하는 단계를 포함하는, 식 I의 화합물을 단일한 입체이성질체의 결정 형태로 제조하는 방법; 결정형의 식 I의 화합물 및 화합물의 염; 상기 염을 포함하는 약학 조성물; 식 I의 화합물을 제조하는 공정의 중간산물의 제조 방법과 중간산물을 제공한다. The present invention relates to a process for the preparation of a compound of formula I by deprotecting an amine group in a mixture of a compound of the formula IIa or a compound of the formula IIa and a compound of the formula IIb and isolating the compound of the formula I from the reaction mixture, In the form of an isomeric crystal form; Salts of compounds and compounds of formula I in crystalline form; A pharmaceutical composition comprising said salt; A process for the preparation of an intermediate product of the process for preparing a compound of formula I and an intermediate product are provided.

Mutilin-Derivative Substituted at Position 12

A position 12-substituted mutilin derivative, a novel mutilin analogue, is provided that exhibits strong antimicrobial activity against abroad spectrum of Gram-positive or Gram-negative bacteria, including various drug-resistant bacteria, as well as intermediates for the production of such mutilin derivatives. Specifically, a mutilin derivative or an acid-addition salt thereof is provided that is represented by the following chemical formula (1): (wherein R 1 is a hydrogen atom, a formyl group, a substituted or unsubstituted lower alkyl group, an aralkyl group whose aromatic ring may be optionally substituted, a heteroaralkyl group whose aromatic ring may be optionally substituted or a lower alkyloxycarbonyl group; and R 2 is a hydrogen atom, a lower alkyl group or an aralkyl group whose aromatic ring may be optionally substituted) (R 1 is neither an ethyl group nor a vinyl group).

Pleuromutilin derivatives and their use as antimicrobials

12-EPI-Proiromutilin

Pluromutilin complex

Process for the preparation of a mutilin derivative

Crystalline forms of pleuromutilin compound, pharmaceutical composition containing the same, and process for preparing the same

Process for the preparation of pleuromutilins

Process for the preparation of a Compound of formula I in the form of a single stereoisomer in crystalline form, comprising deprotecting the amine group in a Compound of formula IIa or in a mixture of a compound of formula IIa With a compound of formula IIb and isolating a Compound of formula I from the reaction mixture; Compounds and salts of Compounds of formula I in crystalline form; pharmaceutical compositions comprising such salts; processes for the preparation of intermediates and intermediates in a process for the preparation of a Compound of formula I.

Pleuromutilin complexes

Complexes and pharmaceutical preparations containing complexes of the pleuromutilin derivative of formula I in free base or in acid addition or quaternary salt form and cyclodextrin are described. They can be prepared by complexing the above pleuromutilin compound with an appropriate cyclodextrin. They are indicated for use as pharmaceuticals, e.g. as antibiotics, especially in veterinary medicine, e.g. as feed additives.

Process for the preparation of pleuromutilins

New pleuromutilin derivative and its use

本发明涉及反式－3－氨基环丁基(1S，2R，3S，4S，6R，7R，8R，14R)－4－乙烯基－3－羟基－2，4，7，14－四甲基－9－氧代三环[5.4.3.01，8]十四烷－6－基亚氨基二羧酸酯的L－酒石酸盐(化合物IA)。化合物IA用于治疗多种疾病和病症，如呼吸道以及皮肤和皮肤组织感染。因此，本发明还涉及包含化合物IA的药物组合物。本发明还涉及使用化合物IA或包含化合物IA的药物组合物治疗呼吸道以及皮肤和皮肤组织感染的方法。

Pleuromutilins

Carbamoyloxy derivatives of methiline and their use as antimicrobial agents

본 발명은 하기 화학식 (1A)의 화합물 또는 약제학적으로 허용되는 염, 및 이들의 유도체의 머틸린의 유도체에 관한 것이며, 이들은 박테리아 감염 치료에 유용하다. (화학식 1A) 상기 식에서, R은 에틸 또는 비닐이며, Y는 N-원자가 비치환되거나, 일치환 또는 이치환된 카르바모일옥시기이다.

Pleuromutilin derivatives and their use as antimicrobials

A compound of formula (I) or of formula (II) wherein X is oxygen or sulfur, and Y is a residue of pipecolic acid or a residue of an amino acid, preferably a naturally occurring amino acid.

Process for the preparation of pleuromutilins

12-epi-pleuromutilins

SALT OF THE PLEUROMUTILINE COMPOUND AS L-TARTRATE, NON-ESTEQUIMETRIC HYDRATION OF THE SAME PHARMACEUTICAL COMPOSITION THAT INCLUDES IT AND ITS USE TO PREPARE A MEDICINAL PRODUCT

Sal del compuesto pleuromutilina que es el L-tartrato de trans-3-aminociclobutilo y (1S,2R,3S,4S,6R,7R,8R,14R)-4-etenil-3-hidroxi-2,4,7,14-tetrametil-9-oxotriciclo[5.4.3.01,8]tetradec-6-il imidodicarbonato (Compuesto 1A), en forma de estructura de estado solido. Sus solvatos, hidratos o mezclas e hidratos no estequiométricos con 2 a 7% de agua. La sal posee un patron de XRPD que tiene máximos característicos en las siguientes posiciones:6,7-+0,1 (°2theta), 10,0 -+0,1 (°2theta), 11,7+- 0,1(°2theta), 13,2 +- 0,1 (°2theta), 13,7 +- 0,1 (°2theta), 14,2 +- 0,1 (°2theta), 20,4 +- 0,1 (°2theta) y 23,5 +- 0,1 (°2theta). Composicion farmacéutica que la comprende y su uso para preparar un medicamento util para el tratamiento de infecciones respiratorias y de la piel. Salt of the pleuromutilin compound which is trans-3-aminocyclobutyl L-tartrate and (1S, 2R, 3S, 4S, 6R, 7R, 8R, 14R) -4-ethenyl-3-hydroxy-2,4,7,14 -tetramethyl-9-oxotricyclo [5.4.3.01.8] tetradec-6-yl imidodicarbonate (Compound 1A), in the form of a solid state structure. Its solvates, hydrates or mixtures and non-stoichiometric hydrates with 2 to 7% water. The salt has an XRPD pattern that has characteristic maximums in the following positions: 6.7- + 0.1 (° 2theta), 10.0 - + 0.1 (° 2theta), 11.7 + - 0.1 (° 2theta), 13.2 + - 0.1 (° 2theta), 13.7 + - 0.1 (° 2theta), 14.2 + - 0.1 (° 2theta), 20.4 + - 0 , 1 (° 2theta) and 23.5 + - 0.1 (° 2theta). Pharmaceutical composition that comprises it and its use to prepare a useful medicine for the treatment of respiratory and skin infections.

Pleuromutilin derivatives and their use as antimicrobials

식 (I) 또는 식 (II)의 화합물: 상기 식에서, X는 산소 또는 황이고, Y는 피페콜산 잔기 또는 아미노산 잔기이며, 바람직하게는 천연 아미노산이다. A compound of formula (I) or formula (II): In this formula, X is oxygen or sulfur, Y is a piperathic acid residue or amino acid residue, preferably a natural amino acid.

Process for the preparation of pleuromutilins

Process for the preparation of a compound of formula I in the form of a single stereoisomer in crystalline form, comprising deprotecting the amine group in a compound of formula IIa or in a mixture of a compound of formula IIa with a compound of formula IIb and isolating a compound of formula I from the reaction mixture; compounds and salts of compounds of formula I in crystalline form; pharmaceutical compositions comprising such salts; processes for the preparation of intermediates and intermediates in a process for the preparation of a compound of formula I.

Pleuromutilin derivative with amino side chain as well as preparation method and application thereof

本发明属于药物化学领域，公开了一种具有氨基侧链的截短侧耳素衍生物及其制备方法与应用。所述的具有氨基侧链的截短侧耳素衍生物，为式2所示结构化合物或其药学上可接受的盐，以及式2所示结构化合物或其药学上可接受的盐的溶剂化合物、对映异构体、非对映异构体、互变异构体或其任意比例的混合物，包括外消旋混合物。该截短侧耳素衍生物具有良好的抗菌活性，特别适合作为新型抗菌药物用于动物或人全身系统感染。

Pleuromutilin derivative having 2-amino phenyl mercaptan side chain as well as preparation method and application thereof

A pleuromutilin derivative having a 2-amino phenyl mercaptan side chain as well as a preparation method and application thereof are provided. The derivative has a structure represented by formula 2 or formula 3, wherein, R1, R2 and R3 are each independently selected from a hydrogen atom, hydroxyl, amino, sulfydryl, hydroxymethyl, amine methyl, nitro, halogen, trihalogenated methyl, methyl, natural amino acid acylamino and C1-6 alkoxy. The plueuromutilin derivative in the disclosure has good activity of inhibiting drug-resistant Staphylococcus aureus and mycoplasma , and is especially suitable for preventing and treating infectious diseases caused by human or animal mycoplasma or drug-resistant Staphylococcus aureus or multidrug resistant bacteria as a novel antibacterial drug.

Pleuromutilin complexes their preparation and pharmaceutical compositions containing them

Complexes and pharmaceutical preparations containing complexes of the pleuromutilin derivative of formula I <CHEM> in free base or in acid addition or quaternary salt form and cyclodextrin are described. They can be prepared by complexing the above pleuromutilin compound with an appropriate cyclodextrin. They are indicated for use as pharmaceuticals, e.g. as antibiotics, especially in veterinary medicine, e.g. as feed additives.

New compounds

Pleuromutilin alpha-cyano cinnamic acid ester compounds with drug-resistant bacteria resisting activity and preparation method and application thereof

本发明公开了一类具有抗耐药菌活性的截短侧耳素α‑氰基肉桂酸酯类化合物及其制备方法与应用，属于医药化学技术领域。首先将含不同取代基的苯甲醛类化合物制成相对应的α‑氰基肉桂酸，再将含不同取代基的α‑氰基肉桂酸与截短侧耳素溶于有机溶剂或离子液体中发生反应，合成了一类未见报道的截短侧耳素α‑氰基肉桂酸酯类化合物。该合成方法成熟，反应条件简单，反应产率较高，适用于工业化生产。体外抗菌实验表明本发明合成的截短侧耳素α‑氰基肉桂酸酯类化合物具有较强的抗菌活性；体外细胞毒性实验表明本发明合成的截短侧耳素α‑氰基肉桂酸酯类化合物具有较高的安全性，对由致病菌，尤其是耐药菌引起的感染性疾病具有较好的治疗作用及应用前景。

Hydrolysis method for pleuromutilin

本发明涉及一种截短侧耳素的水解方法，该方法采用向截短侧耳素的乙酸丁酯提取液中加入硫酸水溶液，在搅拌状态下升温至80～90℃，反应5～6h；反应完毕后，静置分层，将上层乙酸丁酯相在65℃~70℃真空浓缩；将浓缩液用热水洗涤2～3次，然后加入干燥剂脱水，过滤；将过滤液缓慢降温至0～5℃，产品析出，过滤干燥得截短侧耳素水解产物。本发明采用低浓度的硫酸水溶液进行截短侧耳素的水解，避免使用了强碱，降低了操作风险；其次，本发明采用直接浓缩结晶，未引入第二种溶剂，减少了有机溶媒的使用，生产周期较短，操作简单，产品收率较高，污染较少，适用于工业化生产。

Novel pleuromutilin derivatives

12-epi-pleuromutilins

本发明提供选自14‑O‑[((烷基‑、环烷基‑、杂环烷基‑、杂芳基‑或芳基)‑硫烷基)‑乙酰基]‑12‑表‑木替灵或14‑O‑[((烷基‑、环烷基‑、杂环烷基‑、杂芳基‑或芳基)‑氧基)‑乙酰基]‑12‑表‑木替灵的化合物，任选地呈盐和/或溶剂合物的形式，和用于制备这样的化合物的方法和它们作为药物的用途。

Pleuromutilin complexes

Complexes and pharmaceutical preparations containing complexes of the pleuromutilin derivative of formula I in free base or in acid addition or quaternary salt form and cyclodextrin are described. They can be prepared by complexing the above pleuromutilin compound with an appropriate cyclodextrin. They are indicated for use as pharmaceuticals, e.g. as antibiotics, especially in veterinary medicine, e.g. as feed additives.

Pleuromutilin derivatives and their production

Pleuromutilin derivatives

A compound of formula (I), in which each of R 1 and R 2 is independently hydrogen, alkyi or, together with the carbon atom to which it is bonded, a cycloalkyl; and each of R 3 and R 4 is independently hydrogen, alkyl or substituted alkyl. The compounds are useful intermediates and prodrugs.

Mutilin derivatives adn their use as pharmaceutical

Valnemulin crystalline salts with organic acids

Azabicyclic carbamoyloxy mutilin derivatives for antibacterial use

Compounds of formula (3), and pharmaceutically acceptable salts and derivatives thereof, in which R1 is vinyl or ethyl; and R2 is a group R3, R4CH2-, or R5R6C=CH-; wherein each of R?3 and R4¿ is an azabicyclic ring system or R?5 and R6¿ together with the carbon atom to which they are attached form an azabicyclic ring system, are useful in the prevention and treatment of microbial infections.

Carbamoyloxy derivatives of mutiline and their use as antibacterials

Derivatives of mutiline of formula (1A) and pharmaceutically acceptable salts and derivatives thereof, in which R 1 is ethyl or vinyl, Y is a carbamoyloxy group, in which the N-atom is unsubstituted, or mono- or di-substituted, are useful in the treatment of bacterial infections.

Organic compounds

14-O—[(((C 1-6 )Alkoxy-(C 1-6 )alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O—[(((C 1-6 )Mono- or dialkylamino-(C 1-6 )alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Hydroxy-(C 1-6 )-alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Formyl-(C 0-5 )-alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Guanidino-imino-(C 1-6 )alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Ureido-imino-(C 1-6 )alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Thioureido-imino-(C 1-6 )alkyl)-phenylsulfanyl)-acetyl]-mutilins, 14-O-[((Isothioureido-imino-(C 1-6 )alkyl)-phenylsulfanyl)-acetyl]-mutilins and their use as pharmaceuticals.

PLEUROMUTILINS.

SE PRODUCEN COMPUESTOS DE FORMULA I: EN DONDE R1 Y R2 SON LO MISMO O DIFERENTES Y CADA UNO DE ELLOS REPRESENTA HIDROGENO, ALQUILO, ALQUENILO, CICLOALQUILO, ARILO O ARALQUILO, MEDIANTE UN NUEVO PROCESO AMBIENTALMENTE ACEPTABLE. COMPOUNDS OF FORMULA I ARE PRODUCED: WHERE R1 AND R2 ARE THE SAME OR DIFFERENT AND EACH OF THEM REPRESENTS HYDROGEN, ALKYL, ALKYL, ARYL OR ARKYLLL, THROUGH A NEW ENVIRONMENTALLY PROCESS.

Carbamoyloxy derivatives of mutiline and their use as antibacterials

Complex of pleuromutilin derivative and a cyclodextrin; pharmaceutical preparations

Complexes and pharmaceutical preparations containing complexes of the pleuromutilin derivative of formula I <CHEM> in free base or in acid addition or quaternary salt form and cyclodextrin are described. They can be prepared by complexing the above pleuromutilin compound with an appropriate cyclodextrin. They are indicated for use as pharmaceuticals, e.g. as antibiotics, especially in veterinary medicine, e.g. as feed additives.

Pleuromutilin derivatives and their use as antimicrobials

CRYSTALLINE FORM OF A PLUROMUTYLIN.

Mevcut buluş, kristalin 14-O-{[(4-amino-2-hidroksi-sikloheksil)-sulfanil]-asetil}-mutilin, bunun hazırlanması için yeni prosesler ve bunun kristalin tuzları ile ilgilidir. The present invention relates to crystalline 14-O - {[(4-amino-2-hydroxy-cyclohexyl) -sulfanyl] -acetyl} -mutiline, novel processes for its preparation and crystalline salts thereof.

Pleuromutilin salicylic acid ester with antibacterial activity and a method of preparing the same

A compound with anti-drug resistant bacteria activity having the following formula (I):is disclosed. The methods of preparing the compound of formula (I) are also disclosed.

Preparation method of docetaxel four-membered ring opening product

本发明公开了一种多西他赛四元环开环产物的制备方法，属于抗癌药品制备技术领域，其技术方案包括以下步骤：步骤S1、将多西他赛用二氯甲烷溶清，加入四氯化锡的二氯甲烷溶液，搅拌反应，反应结束之后，在反应液中加入碳酸钾溶液，继续搅拌，萃取收集有机相，最后浓缩有机相；步骤S2、以硅胶正相柱对有机相进行柱层析纯化，之后收集产物，最后将产物浓缩得浓缩物；步骤S3、将浓缩物进行制备液相纯化收集目标段，浓缩得到白色固体，抽滤、干燥得目标产物，本发明的优点是通过开环反应设计制备多西他赛RO‑2的反应路线，反应路线直接，反应条件容易达成，目前产物整体收率高。

Pleuromutilin (phenylthio)acetic acid ester with anti-drug resistant bacteria activity and a method of preparing the same

A compound with anti-drug resistant bacteria activity having the following formula (I): is disclosed. The methods of preparing the compound of formula (I) are also disclosed.

Multiline derivatives of carbamoyl azabicycles for antibacterial use

Carbamoyloxy derivatives of mutiline with antibacterial activity, pharmaceutical compns. contg. them and process for preparing the said compds.

一种双溶媒提取截短侧耳素的方法

本发明为一种双溶媒提取截短侧耳素的方法。一种双溶媒提取截短侧耳素的方法，包括以下步骤：(1)浸提：向菌丝体中加入甲醇溶液进行第一次浸提，浸提后抽取上清液；加入甲醇溶液进行第二次浸提，浸提后抽取上清液；加入甲醇溶液进行第三次浸提，浸提后压滤，合并上清液和滤液，得浸提液；(2)在不低于0.05MPa下，所述的浸提液加热至48‑52℃，真空蒸发回收甲醇后，水洗蒸发回收甲醇；(3)所述的步骤(3)中水洗蒸发后的浸提液采用乙酸乙酯转相，再依次进行水洗、盐水洗；(4)将所述的盐水洗后的浸提液进行浓缩结晶处理后，进行固液分离、干燥。本发明所述的一种双溶媒提取截短侧耳素的方法，该提取方法产率高，损耗低，提出的截短侧耳素纯度高。

Antimicrobial and antitubercular compounds

Infections caused by Mycobacterium tuberculosis kill more than 1.8 million people each year. While the persistence of this pathogenic bacterial species and the emergence of multidrug resistant strains have created an urgent need for new TB therapies, a new TB-specific drug has not been developed in over 40 years. The disclosure herein provides short and scalable syntheses of small molecules, and small molecules as new therapeutics for eradicating this life threatening pathogen.

Antibakteriális hatású mutilin-karbamoil-oxi-származékok, ezeket tartalmazó gyógyszerkészítmények és eljárás a vegyületek előállítására

A jelen találmány új (3) általánős képletű vegyületekre, azőkelőállítására alkalmas eljárásőkra, és a vegyületeket tartalmazógyógyászati készítményekre vőnatkőzik. A vegyületek antibakteriálisterápiában alkalmazhatók. A (3) általánős képletben R1 jelentése vinil- vagy etilcsőpőrt; R2 és R3 jelentése hidrőgénatőm, adőtt esetben helyettesített 1-6szénatőmős nyílt láncú, 3-8 szénatőmős gyűrűs szénhidrőgéncsőpőrt,adőtt esetben helyettesített heterőgyűrűs vagy arilcsőpőrt, vagy R2 ésR3 együtt egy adőtt esetben helyettesített 3-8 gyűrűatőmős gyűrűscsőpőrtőt alkőt, amely adőtt esetben tővábbi heterőatőmőt tartalmaz ésadőtt esetben karbőciklűsős vagy heterőciklűsős gyűrűvel kőndenzált,vagy R2 jelentése a fenti egy vegyértékű csőpőrtők egyike és R3 jelentése -SO2R4, -COR5, -OR5 vagy -NR6R7 általánős képletűcsőpőrt, amelyekben R4 jelentése adőtt esetben helyettesített 1-6 szénatőmős nyílt láncú,3-8 szénatőmős, gyűrűs szénhidrőgéncsőpőrt, heterőgyűrűs csőpőrt,arilcsőpőrt, 1-6 szénatőmős alkil-aminő-csőpőrt vagy aril-aminőcsőpőrt; R5 jelentése hidrőgénatőm, adőtt esetben helyettesített 1-6 szénatőmősnyílt láncú, 3-8 szénatőmős, gyűrűs szénhidrőgéncsőpőrt, heterőgyűrűscsőpőrt vagy arilcsőpőrt; R6 és R7 jelentése hidrőgénatőm, 1-6 szénatőmős nyílt láncú, 3-8szénatőmős gyűrűs szénhidrőgén-csőpőrt, heterőgyűrűs csőpőrt,arilcsőpőrt, vagy R6 és R7 együtt egy adőtt esetben helyettesített 3-8 gyűrűatőmősgyűrűs csőpőrtőt alkőt, amely adőtt esetben tővábbi heterőatőmőttartalmaz, és adőtt esetben szénhidrőgéngyűrűvel, heterőgyűrűs vagyarőmás csőpőrttal kőndenzált. ŕ

Small molecules active against gram-negative bacteria

Disclosed are novel compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

一种二萜衍生物及其制备方法、药物组合物和应用

本发明公开了一种二萜衍生物及其制备方法、药物组合物和应用，该二萜衍生物结构如式Ⅰ所示，R 1 为氧、羟基或酯基；R 2 为氧、羟基或酯基；R 3 为乙基或乙烯基。本发明通过半合成修饰的手段获得了一种新型二萜衍生物，制备过程简便易行，通过药理实验发现本发明提供的二萜衍生物均表现出强效的抑制多种肿瘤细胞增殖的活性，具有明显的体外和体内的抗癌活性，并且普遍不具有抗生素活性，适合用于抗肿瘤药物的开发。

Small molecules active against gram-negative bacteria

Disclosed are novel compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

一种以二乙氨基乙硫醇合成液生产泰妙菌素的方法

本发明涉及一种兽用原料药的化学合成方法，特别涉及以低浓度二乙氨基乙硫醇生产泰妙菌素的方法。本发明所述方法包括以环硫乙烷和二乙胺反应制备二乙氨基乙硫醇合成液，然后将二乙氨基乙硫醇合成液与对甲基苯磺酸截短侧耳素酯直接反应，依次通过还原剂还原、碱性洗涤、中性洗涤、转相等提取步骤，制得高纯度泰妙菌素。本发明可以浓度为25%‑65%的二乙氨基乙硫醇与对甲基苯磺酸截短侧耳素酯直接反应生成泰妙菌素，这样对二乙氨基乙硫醇的质量要求将大大降低，同时使其生产工艺的安全性也大大提高，工序简单、原料易得、成本低，从而使得本发明非常适合工业化大生产的应用。

Νεα παραγωγα πλευρομουτιλινης

Ενώσεις πλευρομουτιλίνης του τύπου (Α) & (Β) έχουν χρήση σε αντι-βακτηριακή θεραπεία.

一种以异硫脲盐与对甲基苯磺酸截短侧耳素酯制备泰妙菌素的方法

本发明涉及一种兽用原料药泰妙菌素的化学合成方法，特别涉及一种以异硫脲盐与对甲基苯磺酸截短侧耳素酯制备泰妙菌素的方法。本发明所述方法包括以溴氯乙烷与二乙胺制备的氨基氯乙烷和硫脲反应制备异硫脲盐，以截短侧耳素和对甲苯磺酰氯反应制备对甲基苯磺酸截短侧耳素酯，后将异硫脲盐加入对甲基苯磺酸截短侧耳素酯，反应液经碱性洗涤、中性洗涤、转相等提取步骤，制得高纯度泰妙菌素。本发明完全避开了受监管的危险中间体二乙氨基乙硫醇，采取较温和的路线制备泰妙菌素，大大降低了产品管控成本，原料易得，从而使得本发明非常适合工业化大生产的应用。

一种截短侧耳素的改性方法及其在泰妙菌素制备中的应用

本发明涉及制备活性药物成分的截短侧耳素的精制方法，特别的涉及脱除截短侧耳素中2,3‑截短侧耳素环氧化物的方法，从而降低泰妙菌素中环氧化物的含量。向截短侧耳素溶液中加入开环所用的催化剂，环氧化物与催化剂的质量比为1：1.5‑4.5，反应温度20℃‑180℃，反应时间15‑60分钟。催化剂的选择与反应温度相关，中低温条件下，催化剂选用强酸类物质；中高温条件下，催化剂选用三氧化二铝和二氧化硅的混合物或者碱金属碘化物。本发明通过在催化剂条件下，将环氧化物上的环氧键开环异构成酮，可使环氧化物的含量控制在一个极低的水平，从而得到高纯度的截短侧耳素，可以稳定地制备获得高纯度的泰妙菌素。

Carnamoyloxy derivate von mutilin und deren verwendung als antibakterielles mittels

一种泰妙菌素的合成方法及其中间体

本发明提供了一种泰妙菌素的合成方法及其中间体。所述合成方法以乙烯巯基截短侧耳素(式(Ⅰ)化合物)和二乙胺为原料，在光催化剂的作用下光照反应，合成出泰妙菌素。所述乙烯巯基截短侧耳素的合成以巯基截短侧耳素(式(Ⅱ)化合物)和乙炔为原料，在光催化剂的作用下光照反应生成。本制备方法避免使用具有恶臭味道的二乙氨基乙硫醇和环硫乙烷，反应活性高，条件温和，后处理简单，生产成本比现有工艺低，工艺绿色环保。

一种泰妙菌素的合成方法及其中间体

本发明提供了一种泰妙菌素的合成方法及其中间体。所述合成方法以乙烯巯基截短侧耳素(式(Ⅰ)化合物)和二乙胺为原料，在光催化剂的作用下光照反应，合成出泰妙菌素。所述乙烯巯基截短侧耳素的合成以巯基截短侧耳素(式(Ⅱ)化合物)和乙炔为原料，在光催化剂的作用下光照反应生成。本制备方法避免使用具有恶臭味道的二乙氨基乙硫醇和环硫乙烷，反应活性高，条件温和，后处理简单，生产成本比现有工艺低，工艺绿色环保。

一种二萜衍生物及其制备方法、药物组合物和应用

本发明公开了一种二萜衍生物及其制备方法、药物组合物和应用，该二萜衍生物结构如式Ⅰ所示，R 1 为苯基、链状脂肪烃、环状脂肪烃或含杂原子芳香环。本发明获得了一种新型二萜衍生物，制备过程简便易行，对多种肿瘤细胞增殖均有一定抑制作用，适合用于抗肿瘤药物的开发。

Azabicycliache carbamoyloxy mutilin derivate als antibakterielles mittel

抗菌活性を有するプロイロムチリン誘導体

式（ＩＡ）及び（ＩＢ）のプロイロムチリン化合物は抗菌治療において有用である。

抗菌活性を有するプレウロムチリン馬尿酸エステルおよびその製造方法

Pleuromutilin salicylic acid ester with antibacterial activity and a method of preparing the same

A compound with anti-drug resistant bacteria activity having the following formula (I): (I) is disclosed. The methods of preparing the compound of formula (I) are also disclosed.

Mutilinderivate und ihre verwendung als arzneimittel

Pleuromutilin-derivate

Neue pleuromutilinderivate

Crystal form of valnemulin hydrochloride hydrate, preparation method therefor, and pharmaceutical composition containing crystal form

Senyawa terbaru

一类具有抗耐药菌活性的截短侧耳素肉桂酸酯类化合物及其合成方法和应用

本发明公开了一类具有抗耐药菌活性的截短侧耳素肉桂酸酯类化合物及其合成方法，属于医药化学领域。该类化合物以截短侧耳素、肉桂酸类化合物为原料，反应过程用N 2 保护，在离子液体中反应或者在催化剂作用下于有机溶剂中反应，合成了一类未见报道的截短侧耳素肉桂酸酯类化合物。该合成方法操作安全性高，反应条件温和，适用于工业化生产。经初步生物活性测试和安全性评价表明该类截短侧耳素肉桂酸酯化合物有较好的抗耐药菌活性和安全性，可应用于治疗感染性疾病，特别是耐药菌引起的感染性疾病，具有很好的医药开发价值。

一种泰妙菌素半抗原tmlh、人工抗原、抗体及其制备方法和应用

本发明公开了一种泰妙菌素半抗原TMLH、人工抗原、抗体及其制备方法和应用。本发明首先提供了一种泰妙菌素半抗原TMLH，进一步利用该泰妙菌素半抗原与载体蛋白偶联得到的人工抗原作为免疫原免疫小鼠，制备得到泰妙菌素单克隆抗体。本发明制备得到的抗体的效价、特异性、亲和力都比较好，其对泰妙菌素的最低检测限为0.16ng/mL，IC 50 为1.75ng/mL，线性范围为0.47～6.52ng/mL；具有简便快速、特异性强、线性范围广，灵敏度高的特点，在泰妙菌素的快速有效检测中具有良好的应用前景和广阔的发展空间。

Neue pleuromutilin derivate