METHOD FOR MANUFACTURING 7alpha-ALKOXYOXACEPHEM INTERMEDIATE COMPOUND

The present disclosure provides a method for preparing a 7α-alkoxyoxacephem intermediate compound, the method comprising a process (S1) including: reacting a compound represented by a following chemical formula 1 with a halogen compound in an organic solvent to form a reaction product such that unreacted halogen compound remains; and adding metal alkoxide and reducing agent to the reaction product with the unreacted halogen compound remaining, thereby to produce a compound represented by a following chemical formula 2: 2. The method of claim 1 , wherein a content of the organic solvent is equal to a content of the compound expressed by the chemical formula 1 or is 100 times or less larger than the content of the compound expressed by the chemical formula 1.3. The method of claim 1 , wherein the halogen compound includes at least one selected from a group consisting of chlorine claim 1 , bromine claim 1 , N-iodosuccinimide claim 1 , N-bromosuccinimide claim 1 , N-chlorosuccinimide claim 1 , N-fluorosuccinimide claim 1 , tert-butyl hyperchloride claim 1 , or a combination thereof.4. The method of claim 3 , wherein a content of the halogen compound is in a range of 2 to 4 mol based on a content of the compound expressed by the chemical formula 1.5. The method of claim 3 , wherein a reaction temperature in the (a) is in range of −50 to 50° C.6. The method of claim 1 , wherein the metal alkoxide includes at least one selected from a group consisting of lithium methoxide (LiOCH) claim 1 , lithium ethoxide claim 1 , lithium tert-butoxide claim 1 , sodium methoxide (NaOCH) claim 1 , potassium methoxide (KOCH) claim 1 , or magnesium methoxide (Mg(OCH)).7. The method of claim 6 , wherein a content of the metal alkoxide is in a range of 3 to 5 mol based on a content of the compound expressed as the chemical formula 1.8. The method of claim 7 , wherein a reaction temperature in the (b) is in a range of −70° C. to −20° C.9. The method of claim 7 , wherein the reducing agent ...

Complexo e processo para preparação de um composto

Process for producing d-configuration crystalline form of sesquisalt of sodium 7beta-[alpha-carboxy-alpha-(n-oxyphenyl) acetamido-7-alpha-methoxy-3-(1-methyl-tetrazol-5-yl) thiomethyl-2-oxadethia-3-cefem-4-carboxyate

The crystalline D-sesquisodium salt of the oxa-β-lactam antibiotic diacid compound of the formula and process for its preparation via acetone dilution ot an aqueous solution of non-crystalline D,L-diacid and D,L-disodium salt.

Synthetic intermediate for cephalosporin analogue

Bicyclic beta-lactame/parabene complexes

A PROCEDURE FOR PREPARING A BENZYL PHENYLACETATE.

Manufacture of substituted benzyl ester

Crystallization

Epimerization of malonic acid esters

A method for preparing isomer of malonate ester is presented. Thus, p-nitrophenyl diazo methane was reacted with 7 β -( α -phydroxyphenyl malonamido)-7 α -methoxy-3-(1-methyl-5-tetrazollyl) thiomethyl-1- dethia-1-oxa-3-Cephem-4-carboxylate to give bis-pnitrobenzyl ester ((R)- and (S)- mixt.). This mixt. was crystallized with dichloromethane contg. Lutidine to give its (S)-isomer.

Method of preparing 7-substituted aminoacetamido-1-oxadethiacephalosporins

Antibacterial 7-substituted aminoacetamido oxadethiacephalosporins of the formula: <IMAGE> [wherein R is substituted amino, substituted phenyl, or 5- or 6-membered hetero ring; Ar is aryl; Y is hydrogen or methoxy; Het is 5- or 6-membered aromatic hetero ring; and Z is hydroxy or carboxy protecting group] preparable e.g. by acylation of 7 alpha -methoxy-7 beta -amino-3-heterocyclic thiomethyl-3-cephem-4-carboxylic acid derivatives, are highly active against gram-positive and gram-negative bacteria, especially those resistant to other cephalosporins and penicillins.

Method of manufacturing 7α-alkoxy oxacephem intermediate compound

본 발명은 7α-알콕시옥사세펨의 제조방법 및 화합물을 개시한다. 본 발명에 따르는 7α-알콕시옥사세펨의 제조방법 및 화합물은 반응식 1에서화학식 1로 나타낸 화합물을 유기용매 중에 할로겐화합물과 MOR′, 환원제를 반응 시킨 후(S1단계) 연속적으로 아세트아미도기화제 또는 티올화제를 반응시켜 하기 화학식 3 또는 화학식 5로 표시되는 화합물을 생성하는 S2단계 및 S3단계를 포함하는 특징이 있는데, 이에 의할 때, 제조공정이 간단하고, 대량생산이 용이함과 동시에 수율이 우수한 효과를 보인다. 반응식 1 (R은 Cl, Br 또는 I이고, R1은 카르복실 보호기로서, 디페닐메틸 (diphenylmethyl), p-메톡시벤질(methoxybenzyl), p-니트로벤질 또는 수소(H)임)1 The present invention discloses a method and compound for the preparation of 7α-alkoxyoxacefem. Method and compound for preparing 7α-alkoxyoxace fem according to the present invention is to react the compound represented by Chemical Formula 1 in Reaction Formula 1 with a halogen compound and MOR ′ in an organic solvent, and reacting a reducing agent (step S1) to continuously acetamidodoating agent or thiol. It is characterized by including steps S2 and S3 to generate a compound represented by the following Chemical Formula 3 or Chemical Formula 5 by reacting a topical agent, and accordingly, the manufacturing process is simple, the mass production is easy, and the yield is excellent. Looks like Scheme 1 (R is Cl, Br or I, R1 is a carboxyl protecting group, diphenylmethyl, p-methoxybenzyl, p-nitrobenzyl or hydrogen (H)) 1

Method of producing esters of s-epimer of 7beta-malonamido-7alpha-methoxy-3-(1-methyltetrazol-5-ulthiomethyl)-1-dethia-1-oxa-3-cephem-4-carboxylic acid

A compound represented by the formula (II) epimerizes by the action of a base and the product is precipitated for shift- wherein Ar is an optionally substituted aryl or heterocyclic group; Tet is an optionally substituted tetrazolyl group and B 1 and B 2 each is ing the equilibrium to yield the corresponding epimer represented by the formula (I): an ester forming group in the field of penicillin or cephalosporin chemistry.

Method of preparing 7-substituted aminoacetamido-1-oxadethia-cephalosporins

Antibacterial 7-substituted aminoacetamido oxadethiacephalosporins of the formula: <IMAGE> [wherein R is substituted amino, substituted phenyl, or 5- or 6-membered hetero ring; Ar is aryl; Y is hydrogen or methoxy; Het is 5- or 6-membered aromatic hetero ring; and Z is hydroxy or carboxy protecting group] preparable e.g. by acylation of 7 alpha -methoxy-7 beta -amino-3-heterocyclic thiomethyl-3-cephem-4-carboxylic acid derivatives, are highly active against gram-positive and gram-negative bacteria, especially those resistant to other cephalosporins and penicillins.

Cephem or carba(dethia)cephem derivatives

FIELD: in chemical and pharmaceutical industries as intermediates for the synthesis of cephalosporin antibiotics, more particularly compounds of the formula II wherein R 1 -(C 2 -C 6 )-alkenyl, or CH 2 , C 2 H 5 OCH 2 CO, C 6 H 5 CH 2 OCO, P-H, t-C 4 H 9 and (C 2 H 5 ) 2 CH. SUBSTANCE: cephem of carba(dethia) cephem derivatives of the formula 1 wherein Z is as defined above, Q-C 6 H 5 OCH 2 CO, C 6 H 5 CH 2 OCO,P=t=C 4 H 9 and (C 6 H 5 ) 2 CH. Reagent 1: oxysubstituted cephem or carba(dethia) cephem derivatives of the formula III wherein Z, Q and P are as defined above. Reagent 2: fluorosulfonic hydride. Reaction conditions: an organic solvent: 0-78 C in the presence of a base. The structural formulae I, II and III: З$ ДУУОС ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) ВИ” 2 044 738 (13) СЛ 51) МК © 070 501/20, 501/22 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 4831927/04, 21.11.1990 (30) Приоритет: 21.11.1989 Ц$ 439767; 603872 (46) Дата публикации: 27.09.1995 (56) Ссылки: Патент С7А М 4520022, кл С (71) Заявитель: Бристоль Мейерз Сквибб Компани (1$) (72) Изобретатель: Стефен Ричард Бейкер[Ц$], Честер Сапино (младший)[Ц$], Грегори Пол РотЦ$] 070501122, 1985.Патент США М 4847373, кл. С (73) Патентообладатель: <“ 070501001, 1989.Патент США М 4870168, кл. С Бристоль Мейерз Сквибб Компани (0$) о 070501/20, 26.09.89 г. (54) ПРОИЗВОДНЫЕ ЦЕФЕМА ИЛИ КАРБА(ДЕТИА)ЦЕФЕМА со (57) Реферат: оксизамещенные производные цефема или © Использование: в карби(детиа)цефема ф-лы (11), где 2, СбиР химико-фармацевтической промышленности в указаны выше. Реагент 2: фторсульфоновый г качестве промежуточных продуктов для гидрид. Условия реакции: органический < синтеза цефалоспориновых антибиотиков, в растворитель, 0 #178°С в присутствии частности соединений ф-лы ||, где К1-(С>-Св) основания. Структура Фф-л 1, |1] о алкиленил, 1 $ или СН5 @ Н С>Н5ОСН>2СО С вН5СН2ОСО Р Н ЕС4Но (С2Н5)2СН Сущность 2 и я, © изобретения: производные цефема или карба 5 н ...

Process for preparing 1-oxadethiacephalosporins

СПОСОБ ПОЛУЧЕНИЯ 1-ОКСАдаТИАЦЕФАЛОСПОРИНОВ общей формулы о RCONH -I -1J СНгХ CQOW где R - свободный фенил, фенил, замещенный нитро- или цианогруппой, метилом или атомом хлора, бензил или феноксиметил;. Е - водород или метоксигруппа; СООВ - карбоксигруппа, бензилоксикарбонил или дифенйлметоксикарбонил; X - водород или галоген или 1-метилтетразол-5-илтиогруппа , отличающийс  тем, что соединение общей формулы о д ксокнЧ-r N z СНгХ о соов где R , Е, СООВ и X имеют приведенные значени ; Z - галоген, окси-, трифторацетокСИ- , фенилтио-, Ci-Cit-алкилтио- или i фенилселенил-группа, подвергают обработке метилатом щелоч СО ного металла, пиперидином, 1,5С -диазабицикло С4,3,01нон-5-еном или 1,5-диазабицикло С5,4,0 ундец-5-еном, когда Z - атом галогена, или тионилхлоридом или хлорокисью фосфора в присутствии пиридина или метилпиридина , или пивалоилизоцианатом, когда Z - окси- или трифторацетоксигруппа , или М-хлорпербензойной 00 О) кислотой или перукс.усной кислотой, когда Z - фенилтио-, ,-алкилтиоили фенилселенил-группа, в раствориа: теле при температуре от -50&amp;deg; С до температуры кипени  ацетона с обратным холодильником в течение времени от 10 мин до 5 сут. METHOD OF OBTAINING 1-OXADATIAATSEPHALOSPORINS of the general formula RCONH-I -1J SNgX CQOW where R is free phenyl, phenyl substituted by nitro or cyano, methyl or chlorine atom, benzyl or phenoxymethyl; E is hydrogen or methoxy; SOOB - carboxy, benzyloxycarbonyl or diphenylmethoxycarbonyl; X is hydrogen or halogen or 1-methyltetrazol-5-ylthio group, characterized in that the compound of the general formula is as follows: where R, E, COOB, and X have the given values; Z - halogen, hydroxy-, trifluoroacetoxy-, phenylthio, Ci-Cit-alkylthio- or i-phenylselenyl-group, is treated with alkali methylate of CO metal, piperidine, 1.5C-diazabicyclo C4,3,01non-5-ene or 1,5-diazabicyclo C5,4,0 undec-5-ene, when Z is a halogen atom, or thionyl chloride or phosphorus oxychloride in the presence of pyridine or methylpyridine, ...

Method of producing azetidinone derivatives

alpha -[3(R)-Substituted amino-4(R)-substituted alkoxy-2-oxo-azetidin-1-yl]- alpha -isopropenylacetate (Ia) and alpha -[3(R)-substituted amino-4(R)-substituted alkoxy-2-oxo-azetidin-1-yl]- alpha -isopropylideneacetate (Ib) prepared from (1R,5S)- alpha -(3-substituted-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl)- alpha -isopropenylacetate or (1R,5S)- alpha -(3-substituted-7-oxo-4-oxa-2,6-diazabicyclo-[3.2.0]hept-2-en-6-yl)- alpha -isopropylideneacetate with a primary alcohol in the presence of an acid. The products are useful intermediates for preparing oxadethiacephalosporins.

Patent JPS609718B2

Method of preparing crystalline form of d-configuration of diammonium salt of 7-beta-/-alpha-carboxy-alpha-p-oxyphenyl acetamido /-7-alpha-methoxy-3-(1-methyltetrazol-5-yl)-thiomethyl-1-oxydethia-3-cephem-4-carboxalic acid

The diamonium salt of the oxa- beta -lactam antibiotic of the formula …<CHEM>… wherein the chiral center of the alpha -carboxy-p-hydroxy-phenylacetyl side chain has the D-configuration in crystalline form substantially free of the L-diammonium salt. This invention also relates to a process for preparing the crystalline D-diammonium salt of the above formula.

1-oxadethiacephalosporin compound and antibacterial agent containing the same

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

Method of preparing 1-oxadethiacephalosporins

PURPOSE:1-Oxadithiacephem cpds. I [ A is amino or protected amino; E is H or methoxy; Y is II(COB is carboxy or protected carboxy; X is H or nucleophile; Z is leaving gp.); the dotted line is alpha or beta-bond], e.g. 7alpha-benzamido3-methyl-1-dithia-1-oxa-3-cephem-4-carboxylic acid benzylester.

Process for preparing 1-oxadethiacephalosporin

Bicyclic 1-oxa-β-lactam diacid antibiotics are described. They are represented by the formula wherein R is an a-carboxysubstituted arylmethyl group of the formula wherein R' is hydrogen, hydroxy, protected hydroxy, acetoxy, C 1 -C 3 alkyl, or halogen; R° is hydrogen or methoxy; R 1 and R,' are hydrogen or a carboxy protecting group; and when R 1 and R 1 ' are hydrogen, the pharmaceutically acceptable salts thereof. The compounds are prepared by reacting the corresponding 3-halomethyl diester with 1-cyanomethyl-1H-tetrazole-5-thiol followed by deesterification.

Method of preparing 7-substituted aminoacetamidooxathiacephalosporins

Antibacterial 7-substituted aminoacetamido oxadethiacephalosporins of the formula: <IMAGE> [wherein R is substituted amino, substituted phenyl, or 5- or 6-membered hetero ring; Ar is aryl; Y is hydrogen or methoxy; Het is 5- or 6-membered aromatic hetero ring; and Z is hydroxy or carboxy protecting group] preparable e.g. by acylation of 7 alpha -methoxy-7 beta -amino-3-heterocyclic thiomethyl-3-cephem-4-carboxylic acid derivatives, are highly active against gram-positive and gram-negative bacteria, especially those resistant to other cephalosporins and penicillins.

Bicyclic beta-lactam/paraben complexes

本发明提供上列通式的复合物，其中：X是氯、氢、乙烯基或-CH 3 ；Z是CH 2 、S或O；n是0～5；Y是苯基或1，4-环己二烯-1-基；R 1 和R 2 是氢或羟基，但其条件是R 1 和R 2 不能同时是氢；而R 3 是-COO-、-COO(C 1 -C 4 烷基)、-NO 2 或-CO-R 4 ，其中R 4 是C 1 -C 4 烷基。

Method of obtaining 3-haloidcephalosporins

СПОСОБ ПОЛУЧЕНИЯ 3-ГАЛОИДДЕФАЛОСПОРИНОВ формулы (I) R-CHiCONH -фенил или феноксигруппа; где R X -хлор или бром, путем взйимодействи  3-оксицефалоспорина формулы (П) . R-CrtiCONH-p-NY LOH NOi COO-CHt где R имеет указанные значени , (с галоидирующим реагентомв безводном инертном органическом растворителе , отличающийс  тем, что, с целью увеличени  выхода целевого продукта, в качестве галоидирующего реагента используют кинетически контролируемьй комплекс триарилфосфита с галогеном формулы (Ш) 0 РХг где Z . - водород или метил; X - имеет указанные значени , .в количестве 1,0-1,1 эквивалента на 1 эквивалент исходного цефалоспорина , и процесс ведут в присутствии пиридина в качестве основани  при температуре от -10 до . Р1 METHOD FOR OBTAINING 3-HALOIDDEPHALOSPORINS of formula (I) R-CHiCONH is phenyl or phenoxy; where R X is chlorine or bromine, by acting on the 3-oxycephalosporin of formula (P). R-CrtiCONH-p-NY LOH NOi COO-CHt where R has the indicated values (with a halogenating reagent in an anhydrous inert organic solvent, characterized in that, in order to increase the yield of the target product, a kinetically controlled triarylphosphite complex with halogen is used as a halogenating reagent where formula is hydrogen or methyl, X - has the indicated values, in the amount of 1.0-1.1 equivalents per equivalent of starting cephalosporin, and the process is carried out in the presence of pyridine as a base at a temperature from - 10 to. P1

Patent JPS6242915B2

Method of producing o-dethia-oxacephalosporines

PURPOSE:To prepare 1-oxadethiacephalosporin useful as an antibiotic or its intermediate, economically, by eliminating 3-position eliminable group of 3-eliminable group-substituted 1-oxadethiacepham compound which is an intermediate of cephalosporin.

Method of producing cephem compounds or their physiologically or aharmaceutically acceptable salts

Novel cephem compounds represented by general formula (I), wherein R1 represents an optionally protected amino group, R2 represents hydrogen or halogen, R3 represents hydrogen or an optionally substituted hydrocarbon residue, R4 represents hydrogen or methoxy, A represents an optionally substituted pyrazol-2-yl group forming a fused ring at positions 1 and 5, and n represents 0 or 1. They possess an excellent antibacterial activity.

Method for synthesizing flomoxef acid

本发明涉及一种氟氧头孢酸的合成方法，方法如下：1)由化合物(I)在有机溶剂中，在有机碱催化下和二碳酸二叔丁酯生成化合物(II)，2)在有机溶剂中和N,N’-二乙基乙二胺的作用下生成化合物(III)，3)通过甲氧基化反应生成化合物(IV)，4)化合物(IV)与四氮唑侧链进行连接得到化合物(V)，5)在三氟乙酸作用下脱去氨基和羧基保护基得到化合物(VI)，6)通过和二氟甲基巯基乙酸活性酯的中间体反应得到氟氧头孢酸(VII)。反应路线如下：

Process for preparing cephalosporinic antibiotics

FIELD: chemical and pharmaceutical industries. SUBSTANCE: process for preparing cephalosporinic antibiotics of formula 1 wherein R is H, t-Bu, is carboxy protecting group, Q is H, or (Ph)CH- is amino protecting group; Z is S or PhOCH 2 CO; PHCH 2 OCO is -CH 2 - alkenyl. Reagent 1: 3-sulfonyloxy containing cephem derivative of formula II wherein Q and R are as defined above; Z is fluorosulfonytoxy, 4-nitrobenzenesulfonyloxy and 4- bromophenylsulfonyloxy. Reagent 2: organostannate of formula: R′ wherein R′Sn(R 2 ) 3 is as defined above and R 1 is lower alkyl. Reaction conditions: aprotic solvent Pd(II) or Pd(0) catalyst in amount of 1-10 mole% per reagent 1. Structure of compounds of formulae I and II: R 2 -. EFFECT: improved properties of the cephalosporinic antibiotics. 000140сС ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (51) МПК ВИ "” 2 070 200 ' 13) Сл С 070 501/20 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 5052625/04, 09.09.1992 (30) Приоритет: 21.11.1989 Ц$ 439767 31.10.1990 4$ 603872 (46) Дата публикации: 10.12.1996 (56) Ссылки: Заявка ЕПВ М 0334590, кл. С 070 501/20, 1989. Патент США М 4870168, кл. С 07 О 501/20, 1989. (62) Первичная заявка, из которой выделена настоящая: 4831927/04 (71) Заявитель: Бристоль-Мейерз Сквибб Компани (ЦЗ) (72) Изобретатель: Стефен Ричард Бейкер[Ц$], Честер Сапино (младший)[Ц$], Грегори Пол РотЦ$] (73) Патентообладатель: Бристоль-Мейерз Сквибб Компани (ЦЗ) (54) СПОСОБ ПОЛУЧЕНИЯ ЦЕФАЛОСПОРИНОВЫХ АНТИБИОТИКОВ (57) Реферат: Использование: в химико-фармацевтической промышленности. Сущность изобретения: способ получения цефалоспориновых антибиотиков формулы 1, где Р - Н, Е Вч-, ач(РА)СН-карбоксизащитная группа, О-Н, РАОСН>2СО или РНСН 20СО-аминозащитная группа 2/-$ или-СН>-, К-(С2-Сз)-алкенил. Реагент 1:3-сульфонилоксисодержащее производное цефема формулы П, где Я и Р имеют указанные выше значения, Г-фторсульфонилокси, 4-нитробензолсульфонилокси и 4-бромфенилсульфонилокси. Реагент 1: ...

Bicyclic complexes beta-lactam/hydroxybenzoic acid, methods of beta-lactams synthesis

FIELD: organic chemistry, antibiotics. SUBSTANCE: invention relates to novel cephalosporins and complexes carbocephalosporin/para-aminobenzoic acid, methods of their synthesis, isolation and purification of antibiotics containing beta-lactam ring. Invention describes complexes of the formula (I) where X means chlorine, hydrogen atom, vinyl or -CH 3 ; Z means CH 2 , S- or O-atom; n = 0-5; Y means phenyl or 1,4-cyclohexadiene-1-yl; R 1 and R 2 mean hydrogen atom or hydroxy-group at condition the they both (R 1 and R 2 ) are not hydrogen atom; and R 3 means -COOH, -COO-(C 1 -C 4 )-alkyl or where R 4 means C 1 -C 4 -alkyl. EFFECT: new cephalosporins and complexes indicated above. 6 cl, 1 tbl, 19 ex Эс с ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) ВИ” 2134 265. (51) МПК 13) СЛ 501/20 С 070 463/16, 471/04, 501/12, 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 94022484/04, 21.06.1994 (30) Приоритет: 28.06.1993 1$ 08084,651 (46) Дата публикации: 10.08.1999 (56) Ссылки: ЗЦ 1034607 А, 07.08.83. ЕР 0341991 А, 15.11.89. ЕР 0369686 А, 23.05.90. ЕР 0311366 А, 12.04.89. 4$ 5142042 А, 25.08.92. (98) Адрес для переписки: 129010, Москва, ул.Б.Спасская, д.25, стр.3, ООО "Союзпатент" (71) Заявитель: Эли Лилли энд Компани (1$) (72) Изобретатель: Джейн Годде Амос (ЦЭ), Джозеф Майкл Инделикато (1$), Кэрол Элейн Пасини (4$), Сьюзн Мэри Ройцель (1$) (73) Патентообладатель: Эли Лилли энд Компани (0$) (54) БИЦИКЛИЧЕСКИЕ КОМПЛЕКСЫ БЕТА-ЛАКТАМ/ ПОЛУЧЕНИЯ БЕТА-ЛАКТАМОВ (57) Реферат: Изобретение относится к новым цефалоспоринам и комплексам карбоцефалоспорин/парааминобензойная кислота, методам их получения и в особенности выделения и ОЧИСТКИ антибиотиков, содержащих бета-лактамное кольцо. Описываются комплексы формулы (М), где Х - хлор, водород, винил или -СНз; 2 - СН2,$ или О; п = 0-5; У - фенил или 1,4-циклогексадиен-1-ил; К. и В> - водород или гидроксигруппа при условии, что оба (Кти ВБ?) не являются водородом; КВ з - ГИДРОКСИБЕНЗОЙНАЯ КИСЛОТА, ...

Method of preparing 7-beta-halogenarylmalonamido-7-alpha-methoxy-heterocyclylthiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid derivatives or their salts with organic or inorganic bases

Antibacterial haloarylmalonamido-1-dethia-1-oxacephalosporins of the following formula: <IMAGE> wherein Ar is <IMAGE> <IMAGE> +TR <IMAGE> (in which Hal and Hal' each is halogen and RO is hydroxy or protected hydroxy); COA and COB each is carboxy or protected carboxy including a pharmaceutically acceptable salt group; and Het is 1-lower alkyl-5-tetrazolyl, 1,3,4-thiadiazol-2-yl or 5-lower alkyl-1,3,4-thiadiazol-2-yl, a pharmaceutical or veterinary composition comprising the said haloarylmalonamido-1-dethia-1-oxacephalosporin and pharmaceutical carrier, and a method for treating or preventing human or veterinary infectious diseases comprising administering an effective amount of the said antibacterial compound.

NEW ANTIBIOTICS OF THE B-LACTAM TYPE, THEIR PREPARATION PROCESS AND THE MEDICINAL PRODUCT CONTAINING THEM

Method of producing esters of cephalosporins or their pharmaceutically acceptable acid-additive salts

Novel esters of pharmacologically active carboxylic acids, which can be cleaved under physiological conditions, in particular of antibiotically active carboxylic acids from the beta -lactam antibiotic field, are described, which are characterised in that the alcohol component of the ester is a group of the general formula <IMAGE> in which R<1> denotes hydrogen or lower alkyl, R<2> denotes hydrogen, lower alkyl, lower haloalkyl, lower alkenyl, lower alkoxycarbonyl, aryl or heteroaryl or, together with R<1> denotes lower alkylene, R<3> denotes hydrogen, lower alkyl or lower alkoxycarbonyl, R<4> denotes the group -COOR<5>, -COR<6>, -SO2-R<6>, -CONR<7>R<8> or -PO(OR<9>)2, R<5> denotes a saturated or unsaturated hydrocarbon radical having up to 12 carbon atoms, in which up to two methylene groups can be replaced by oxygen atoms, or denotes aryl or aryl-lower alkyl, R<6> denotes lower alkyl or aryl, R<7> and R<8> each denotes hydrogen or lower alkyl or together denotes lower alkylene in which a methylene group can be replaced by an oxygen or sulphur atom or by an imino or lower alkylimino group, and R<9> denotes lower alkyl. If a basic substituent is present, these esters can also be present in the form of pharmaceutically acceptable acid addition salts.

Azetidine derivatives

AZETIDINE DERIVATIVES ABSTRACT Azetidine derivatives of the formula: [wherein A is amino or substituted amino; COB is carboxy or pro-tected carboxy; R1 is =C(CH3)2, , or (R4 is alkyl, aryl or aralkyl); OR2 and OR3 independently or taken together with each other represent a ketal; Y is hydrogen or methoxy; Z is hydrogen or halogen] and a process for preparation thereof. Used as intermediates in the preparation of potent antimicrobials l-oxadethiacephalosporins.

PROCESS FOR THE PREPARATION OF OXAZOLINOAZETIDINYLBUTYRIC ACID DERIVATIVES AND NEW PRODUCTS THUS OBTAINED

Procédé de préparation de dérivés d'acide azétidinebutyrique et nouveaux produits ainsi obtenus. Ces produits sont représentés par les formules suivantes : Process for the preparation of azetidinebutyric acid derivatives and new products thus obtained. These products are represented by the following formulas:

Patent FR2511376B1

PROCESS AND PREPARATION OF AZETIDINONES WITH REDUCTION OF AN OXO GROUP AND NEW PRODUCTS THUS OBTAINED

Procédé de préparation d'azétidinones avec réduction d'un groupe oxo et nouveaux produits ainsi obtenus. Dans ce procédé, on soumet des composés ayant la formule : Process for preparing azetidinones with reduction of an oxo group and new products thus obtained. In this process, compounds having the formula:

Patent FR2376861B1

PROCESS FOR PREPARING OXAZOLINOAZETIDINONES FROM 6-AMINOPENICILLANIC ACID AND NEW PRODUCTS THUS OBTAINED

Procédé de préparation de composés d'azétidinone et nouveaux produits ainsi obtenus. Ces composés sont représentés par la formule : Process for the preparation of azetidinone compounds and new products thus obtained. These compounds are represented by the formula:

Patent FR2447924B1

PROCESS FOR THE PREPARATION OF AZETIDINONE COMPOUNDS AND NEW PRODUCTS THUS OBTAINED

Dans ce procédé, on soumet à une méthoxylation un composé ayant la formule : In this process, a compound having the formula is subjected to methoxylation:

ACID DERIVATIVES (OXO CARBONAMIDO HETEROCYCLIC) CEPHEM CARBOXYLIC WITH ANTIBACTERIAL PROPERTIES

DES DERIVES D'ACIDE 7SS-(OXO-CARBONAMIDO HETEROCYCLIQUE SATURE)-3-CEPHEM-4-CARBOXYLIQUE ANTIBACTERIENS ONT LA FORMULE: (CF DESSIN DANS BOPI) (OU R EST L'HYDROGENE OU LE GROUPE METHOXY; R EST L'HYDROGENE OU UN GROUPE NUCLEOPHILE; R EST L'HYDROGENE, UN METAL LEGER OU UN GROUPE DE PROTECTION DU GROUPE CARBOXY; X EST L'OXYGENE, LE SOUFRE, LE GROUPE SULFINYLE OU SULFONYLE; Y EST UN GROUPE ALKYLENE CONTENANT UN OU DAVANTAGE HETEROATOMES; ET Z EST L'HYDROGENE OU UN SUBSTITUANT). 7SS- (SATURATED HETEROCYCLIC OXO-CARBONAMIDO) -3-CEPHEM-4-CARBOXYLIC ANTIBACTERIAL ACID DERIVATIVES HAVE THE FORMULA: (CF DRAWING IN BOPI) (WHERE R IS HYDROGEN OR METHOXYGEN GROUP; R IS HYDROGEN OR METHOXYGENE GROUP; R IS HYDROGEN OR A NUCLEOPHIL GROUP; R IS HYDROGEN, A LIGHT METAL OR A PROTECTIVE GROUP OF THE CARBOXY GROUP; X IS OXYGEN, SULFUR, SULFINYL OR SULPHONYL; Y IS AN ALKYLENE GROUP CONTAINING ONE OR MORE; AND HETEROAT Z IS HYDROGEN OR A SUBSTITUTE).

PROCESS FOR THE PURIFICATION OF OXACEPHALOSPORINS

PROCESS FOR THE PREPARATION OF HALOARYLMALONAMIDOOXACEPHALOSPORINS, NEW PRODUCTS THUS OBTAINED AND THEIR USE FOR THE TREATMENT OF DISEASES DUE TO BACTERIA

Procédé de préparation d'haloarylmalonamidooxacéphalosporines et nouveaux produits ainsi obtenus. Ces haloarylmalonamido-1-déthia-1-oxa-céphalosporines ont la formule suivante : Process for the preparation of haloarylmalonamidooxacephalosporins and new products thus obtained. These haloarylmalonamido-1-dethia-1-oxa-cephalosporins have the following formula:

PROCESS FOR THE PREPARATION OF OXAZOLINES AND NEW PRODUCTS THUS OBTAINED, USEFUL FOR THE SYNTHESIS OF OXADETHIACEPHALOSPORINS

Procédé de préparation d'oxazolines et nouveaux produits ainsi obtenus. Des intermédiares ayant la formule suivante : Process for preparing oxazolines and new products thus obtained. Intermediaries having the following formula:

Patent FR2485018B1

NEW DERIVATIVES OF AZETIDINE

Nouveaux dérivés d'azétidine de formule :

PROCESS FOR THE PREPARATION OF AZETIDINE DERIVATIVES WITH OXO GROUP AND NEW PRODUCTS THUS OBTAINED

Procédé de préparation de dérivés d'azétidine et nouveaux produits ainsi obtenus. Ces composés ont la formule :

PROCESS FOR PREPARATION OF OXAZOLIDINE COMPOUNDS FROM 6-AMINOPENICILLANIC ACID AND NEW PRODUCTS THUS OBTAINED

Procédé de préparation de composés d'oxazolidine et nouveaux produits ainsi obtenus. Ces composés (représentés par les formules suivantes) sont préparés à partir d'acide 6-aminopénicillanique:

Patent FR2511375B1

Preparation of cephalosporin analogue

3-Di-substd.-amino-vinyl 1-oxa-cephalosporin derivs. - are intermediates for 3-thio-vinyl 1-oxa-cephalosporin(s), having good activity against gram-negative and positive bacteria

7-R"-7-R2NH-3-R3R4N-CH=CH-4-R1OOC -1-oxa-ceph-2- or 3-em derivs. of formula (I) are new (where the dotted line indicates a double bond in position 2 or 3; the C atom at position 3 may have E or Z stereoisomerism; R1 is an easily removable protecting gp. and (a) R2 is 2-R6NH-thiazol-4-yl-C(=N-OR5)-CO- gp. (Gp.A) or a protected alpha-carboxyarylacetyl radical Ar-CH(COOR'1)-CO-, R'1 is a protecting gp.; Ar is phenyl, opt. protected para-hydroxyphenyl or 2- or 3-thienyl and R" is H or methoxy in position 7-alpha or (b) R2 is an easily removable protecting gp. and R" is H or methoxy in position 7-alpha or H in position 7-beta; R3, R4 independently are alkyl (opt. substd. by alkoxy or dialkylamino) or phenyl or together with the N atom form a 5- or 6-membered satd. heterocyclic gp., opt. contg. a further N, O or S heteroatom and opt. alkyl substd.). Intermediates for the prepn. of 3-thiovinyl -oxacephalosporins of formula (XVIII). This process is described in detail in the specification, but is not claimed (where R is 2-, 3- or 4-pyridyl (including N oxide derivs.), 2-pyrimidyl, 6-methyl-1-oxido-3-pyridazinyl, opt. 4-substd.-5,6-dioxo -1,4,5,6-tetrahydro-1,2,4- triazin-3-yl, 1-alkyl-5,6-dioxo -1,4,5,6-tetrahydro- 1,2,4-triazin-3-yl, 2-alkyl-5,6-dioxo-1,2,5,6 -tetrahydro-1,2,4-triazin-3-yl, opt. 6-substd.-2-alkyl -2,5-dihydro-5-oxo-1,2,4 -triazin-3-yl, 1-amino-1,2-dihydro-2-oxo -4-pyrimidinyl, substd.-1,3,4-thiadiazol-5-yl, 1-substd.-5-tetrazolyl, opt. 3-substd.-1-alkyl-1,3,4 -triazol-5-yl and R' is a gp. derived from Gp.A. Details of the substits. etc. are given). (XVIII) are antibacterials having good activity against both gram-positive and gram-negative bacteria.

Patent FR2375238B1

NEWS AZETIDINONES

ACID DERIVATIVES (OXO CARBONAMIDO HETEROCYCLIC) CARBXYL CEPHEM WITH ANTIBACTERIAL PROPERTIES

Patent FR2476091A1

DES COMPOSES REPRESENTES PAR LA FORMULE : (CF DESSIN DANS BOPI) OU R EST UN ATOME D'HYDROGENE OU UN GROUPE ALKYLE INFERIEUR, ALKENYLE INFERIEUR, ALKYNYLE INFERIEUR OU ALKYL(INFERIEUR) THIOALKYLE INFERIEUR, B ET B REPRESENTENT CHACUN UN ATOME D'HYDROGENE OU UN GROUPE OU UN ATOME FORMANT DES GROUPES ESTERS OU DES SELS, B ET B ETANT LES MEMES OU DIFFERENTS, ET HET EST UN GROUPE HETEROCYCLIQUE MONOCYCLIQUE, PRESENTENT UNE FORTE ACTIVITE ANTIBACTERIENNE, SPECIALEMENT CONTRE LES PSEUDOMONAS. COMPOUNDS REPRESENTED BY THE FORMULA: (CF DRAWING IN BOPI) OR R IS A HYDROGEN ATOM OR A LOWER ALKYL GROUP, LOWER ALKENYL, LOWER ALKYNYL OR (LOWER) ALKYL THIOALKYL LOWER, BACYL AND BACYL LOWER ATH, BAC REPRESGEN OR A GROUP OR AN ATOM FORMING ESTER GROUPS OR SALTS, B AND B BEING THE SAME OR DIFFERENT, AND HET IS A MONOCYCLIC HETEROCYCLIC GROUP, SHOWS STRONG ANTIBACTERIAL ACTIVITY, ESPECIALLY AGAINST PSEUDOMONAS.

PROCESS FOR THE PREPARATION OF ANALOGUES OF THIADIAZOLYLCEPHALOSPORIN AND NEW PRODUCTS THUS OBTAINED, WITH ANTIBACTERIAL ACTIVITY

Composés de céphalosporine et leur application. Ces composés ont la formule : Cephalosporin compounds and their application. These compounds have the formula:

Patent FR2476091B1

PROCESS FOR THE PREPARATION OF .beta.-LACTAM COMPOUNDS

ABSTRACT PROCESS FOR THE PREPARATION OF .beta.-LACTAM COMPOUNDS A process for the preparation of a .beta.-lactam having the partial structure (I): (I) wherein R1 is an acyl group, which process comprises treating an imine having the partial structure

DIHYDROTRIAZINYLTHIOOXACEPHALOSPORINS AND THEIR USE AS ANTIMICROBIAL AGENTS

Composés de dihydrotriazinylthiométhyloxacéphem et leur utilisation. Ces composés sont représentés par la formule : Dihydrotriazinylthiomethyloxacephem compounds and their use. These compounds are represented by the formula:

PROCESS FOR THE PREPARATION OF ARLMALONAMIDO-1-OXADETHIACEPHALOSPORINS AND NEW PRODUCTS SO OBTAINED, WITH ANTIBACTERIAL ACTIVITY

FLUOROMETHYLTHIOOXACEPHALOSPORINS AND ANTI-BACTERIAL COMPOSITIONS CONTAINING THEM

PROCESS FOR THE PREPARATION OF B-LACTAME COMPOUNDS

L'INVENTION CONCERNE LA PREPARATION DE DIFFERENTS DERIVES DE B-LACTAME PAR UTILISATION D'AGENTS D'HALOGENATION DE TYPE COMPLEXE CINETIQUE PHOSPHITE DE TRIARYLEHALOGENE. L'UTILISATION DE QUANTITES VARIABLES DE CES DIFFERENTS REACTIFS SUR DIVERSES CEPHALOSPORINES ET PENICILLINES PERMET D'OBTENIR EN PARTICULIER LES IMINO-HALOGENURES, LES DERIVES HALOGENES EN POSITION C-3 DES CEPHALOSPORINES, LES FORMES SULFURES DES CEPHALOSPORINES A PARTIR DES FORMES SULFOXYDES, ETC. LES COMPOSES OBTENUS DANS CES PROCEDES SONT DES ANTIBIOTIQUES INTERESSANTS OU DES INTERMEDIAIRES PERMETTANT DE PREPARER DES ANTIBIOTIQUES INTERESSANTS.

AZETIDINONES

Patent FR2361399B1

Patent FR2345452B1

NOVEL CEPHALOSPORINE DERIVATIVES AND PHARMACEUTICAL COMPOSITION CONTAINING SAME

L'INVENTION A TRAIT AU DOMAINE DE LA CHIMIE PHARMACEUTIQUE. ELLE CONCERNE DES DERIVES NOUVEAUX DE CEPHALOSPORINE DE FORMULE: (CF DESSIN DANS BOPI) DANS LAQUELLE R ET R SONT DES SUBSTITUANTS QUELCONQUES DES POSITIONS RESPECTIVES C-3 ET C-4 DE CEPHALOSPORINES CONNUES DOUEES D'ACTIVITE ANTIBACTERIENNE, X EST UN ATOME DE S OU DE O OU UN RADICAL ORGANIQUE; X EST UN ATOME D'AZOTE OU UN RADICAL ORGANIQUE; R, R ET R SONT DES ATOMES DE H OU DES RADICAUX ORGANIQUES ET R ET R SONT CHOISIS ENTRE DES ATOMES DE H ET D'HALOGENES ET DES RADICAUX ORGANIQUES, ET LEURS SELS D'ADDITION D'ACIDES OU DE BASES ACCEPTABLES DU POINT DE VUE PHARMACEUTIQUE; AINSI QUE DES COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSES ET DES PROCEDES PERMETTANT DE LES OBTENIR. AGENTS ANTIBACTERIENS. THE INVENTION RELATES TO THE FIELD OF PHARMACEUTICAL CHEMISTRY. IT CONCERNS NEW DERIVATIVES OF CEPHALOSPORIN OF FORMULA: (CF DRAWING IN BOPI) IN WHICH R AND R ARE SUBSTITUTES SOME OF THE RESPECTIVE POSITIONS C-3 AND C-4 OF CEPHALOSPORINS KNOWN WITH ANTIBACTERIAL ACTIVITY OF S, X IS AN ATTITUDE OF S AT OR FROM O OR AN ORGANIC RADICAL; X IS AN ATOM OF NITROGEN OR AN ORGANIC RADICAL; R, R AND R ARE H ATOMS OR ORGANIC RADICALS AND R AND R ARE CHOSEN BETWEEN H AND HALOGEN ATOMS AND ORGANIC RADICALS, AND THEIR ADDITIONAL SALTS OF ACIDS OR BASES ACCEPTABLE FROM THE POINT OF PHARMACEUTICAL VIEW; AS WELL AS PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS AND PROCESSES FOR OBTAINING THEM. ANTIBACTERIAL AGENTS.

Patent FR2318157B1

Patent FR2455043B1

Epimerization of malonic acid esters

- Abstract -A compound represented by the formula (II) epimerizes by the action of a base and the product is precipitated for shifting the equiliblium to yield the corresponding epimer represented by the formula (I). (II) (I) wherein Ar is an optionally substituted aryl or heterocyclic group; Tet is an optionally substituted tetrazolyl group and B1 and B2 are each ester forming group in the field of penicillin or cephalosporin chemistry.

Patent FR2370730B1

NEW DERIVATIVES OF CEPHALOSPORINE AND THEIR PREPARATION

NOUVEAUX DERIVES DE LA CEPHALOSPORINE DE FORMULE GENERALEI DANS LAQUELLE: R REPRESENTE UN RADICAL PROTECTEUR D'ACIDE; HAL REPRESENTE UN ATOME D'HALOGENE; X REPRESENTE UN ATOME DE SOUFRE OU D'OXYGENE ET, R REPRESENTE UN RADICAL ACYLE OU UN PROTECTEUR D'AMINE. CES NOUVEAUX PRODUITS SONT UTILISABLES COMME INTERMEDIAIRES POUR LA PREPARATION DE MEDICAMENTS ANTIBACTERIENS DU GROUPE DES CEPHALOSPORINES. (CF DESSIN DANS BOPI) NEW DERIVATIVES OF CEPHALOSPORIN OF GENERAL FORMULA IN WHICH: R REPRESENTS A RADICAL PROTECTIVE ACID; HAL REPRESENTS A HALOGEN ATOM; X IS AN ATOM OF SULFUR OR OXYGEN AND, R IS AN ACYL RADICAL OR AN AMINE PROTECTOR. THESE NEW PRODUCTS CAN BE USED AS AN INTERMEDIATE FOR THE PREPARATION OF ANTIBACTERIAL MEDICINAL PRODUCTS FROM THE CEPHALOSPORINS GROUP. (CF DRAWING IN BOPI)

1-OXACEPHEMES

AZETIDINE DERIVATIVES

Cephalosporin analogues and processes for the preparation thereof

ABSTRACT New cephalosporin analogues and pharmaceutically acceptable salts thereof having antimicrobial activities and useful in the therapeutic treatment of infectious diseases in human beings and animals; the new cephalosporin analogues and pharmaceutically acceptable salts are highly active against a number of pathogenic microorganisms; the analogues have the formula:-

Method of preparing 7-substituted aminoacetamidooxadethiacephalosporins

Antibacterial 7-substituted aminoacetamido oxadethiacephalosporins of the formula: <IMAGE> [wherein R is substituted amino, substituted phenyl, or 5- or 6-membered hetero ring; Ar is aryl; Y is hydrogen or methoxy; Het is 5- or 6-membered aromatic hetero ring; and Z is hydroxy or carboxy protecting group] preparable e.g. by acylation of 7 alpha -methoxy-7 beta -amino-3-heterocyclic thiomethyl-3-cephem-4-carboxylic acid derivatives, are highly active against gram-positive and gram-negative bacteria, especially those resistant to other cephalosporins and penicillins.

Antibacterial compound

NEW OXACEPHALOSPORINS, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM

NOUVELLES CEPHALOSPORINES DE FORMULE GENERALE (I) DANS LAQUELLE R EST PYRIDYLE EVENTUELLEMENT N-OXYDE, PYRIMIDINYL-2, PYRIDAZINYL-3 SUBSTITUE, DIOXO-5,6 TETRAHYDRO-1,4,5,6 TRIAZINE-1,2,4 YL-3 SUBSTITUE EN POSITION -4, ALCOYL-1 TRIAZOL-1,3,4 YL-5 OU TRIAZOL-1,2,4 YL-5 SUBSTITUE, DIOXO-5,6 TETRAHYDRO-1,4,5,6 TRIAZINE-1,2,4 YL-3, SUBSTITUE EN POSITION -1, DIOXO-5,6 TETRAHYDRO-1,2,5,6 TRIAZINE-1,2,4 YL-3, SUBSTITUE EN POSITION -2, ALCOYL-2 DIHYDRO-2,5 OXO-5 TRIAZINE-1,2,4 YL-3 SUBSTITUE OU NON, AMINO-1 DIHYDRO-1,2 OXO-2 PYRIMIDINYL-4 THIADIAZOL-1,3,4 YL-5 SUBSTITUE, TETRAZOLYL-5 SUBSTITUE EN POSITION -1, R EST UN RADICAL (AMINO-2 THIAZOLYL-4)-2 ACETYLE SUBSTITUE OU A-CARBOXYARYLACETYLE ET R EST UN ATOME D'HYDROGENE OU UN RADICAL METHOXY EN POSITION 7A AINSI QUE LEURS SELS, LEUR PREPARATION ET LES MEDICAMENTS QUI LES CONTIENNENT. (CF DESSIN DANS BOPI) NEW CEPHALOSPORINS OF GENERAL FORMULA (I) IN WHICH R IS PYRIDYL POSSIBLY N-OXIDE, PYRIMIDINYL-2, PYRIDAZINYL-3 SUBSTITUTE, DIOXO-5,6 TETRAHYDRO-1,4,5,6 TRIAZINE-1,2,4 YL- 3 SUBSTITUTE IN POSITION -4, ALCOYL-1 TRIAZOL-1,3,4 YL-5 OR TRIAZOL-1,2,4 YL-5 SUBSTITUTE, DIOXO-5,6 TETRAHYDRO-1,4,5,6 TRIAZINE-1 , 2,4 YL-3, SUBSTITUTE IN POSITION -1, DIOXO-5,6 TETRAHYDRO-1,2,5,6 TRIAZINE-1,2,4 YL-3, SUBSTITUTE IN POSITION -2, ALCOYL-2 DIHYDRO- 2,5 OXO-5 TRIAZINE-1,2,4 YL-3 SUBSTITUTE OR NOT, AMINO-1 DIHYDRO-1,2 OXO-2 PYRIMIDINYL-4 THIADIAZOL-1,3,4 YL-5 SUBSTITUTE, TETRAZOLYL-5 SUBSTITUTE IN POSITION -1, R IS A RADICAL (2-AMINO THIAZOLYL-4) -2 ACETYL SUBSTITUTE OR A-CARBOXYARYLACETYL AND R IS A HYDROGEN ATOM OR A RADICAL METHOXY IN POSITION 7A AS WELL AS THEIR SALTS, THEIR PREPARATION AND THE MEDICINAL PRODUCTS THAT CONTAIN THEM. (CF DRAWING IN BOPI)

PROCEDURE FOR THE PREPARATION OF OKSAZOLINE COMPOUNDS SUITABLE FOR THE PREPARATION OF ANTIBACTERIAL EFFECTIVE 1-OKSA DETIACEPHALOSPORINES.

Antibacterial compound

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

Process for producing 7-alpha-aminoacyl-cephalosporin

본 발명은 7-아미노-세프-3-엠-4-카복실산 또는 이의 유도체를 할로겐-부재 용매 속에서 아실화함으로써 할로겐-함유 용매를 사용하지 않으면서 7-α-아미노아실-세팔로스포린을 제조하는 신규 방법에 관한 것이다. The present invention provides the preparation of 7-α-aminoacyl-cephalosporins without the use of halogen-containing solvents by acylating 7-amino-sep-3-m-4-carboxylic acids or derivatives thereof in halogen-free solvents. It relates to a new method to.

1-oxadethiacepham compounds

1-Oxadethiacepham Compounds ABSTRACT Intermediates for preparing an antibacterial 1-dethia-1-oxa-cephalosporins which are represented by the following formula: (wherein R is a monovalent group deducted the carbonyl from an acyl derived from a carboxylic or carbonic acid; Y1 is a divalent group of the following formula: , , , or (in which COB is carboxy or protected carboxy; X is hydrogen or a nucleophilic group; and Z is a leaving group) are prepared from a compound of the following formula: (wherein R and Y1 are as defined above) by the action of an acid. The new compounds of this invention shown by the following formula: (wherein A is amino or substituted amino; E is hydrogen or methoxy; and Y is a divalent group of the following formula: , , , or

Intermediates for cephalosporin analogues

1-oxadethiacephalosporin derivatives and the production thereof

TITLE OF INVENTION New 1-oxadethiacephalosporin derivatives and the production thereof ABSTRACT OF THE DISCLOSURE New antibacterial 1-oxadethiacephalosporin derivatives of the genaral formula wherein R is a heterocyclic group or a group -S-Het where Het denotes a heterocyclic group, Y is a hydrogen atom or a methoxy group; x and y are each an integer of 1 to 3 is produced by a process comprising condensing a l-oxacephem compound of the formula wherein R, Y, y are as defined above; R' is a hydrogen atom or a carboxyl-protecting group; and Z is a halo group, with a sulfur-containing amino acid of the formula wherein x is as defined above,in a solvent and removing, if necessary, the residual protective group from the resultant condensation product. The new l-oxadethiacephalo-sporin derivatives and the pharmaceutically acceptable salts and esters thereof exhibit high and broad "in vitro" and "in vivo" antibacterial activity, particularly against .beta.-lactamase-producing strains of gram-negative bacteria.

Processes for preparation of beta-lactam compounds

1-oxadethia-cephalosporin antibiotics

7-substituted amino acetamido oxadethia-cephalaosporins

Process for the preparation of 7-acylamino-3-hydroxycephem-4-carboxylic acids and 7-acylamino-3-hydroxy-1-dethia-1-oxacephem-4-carboxylic acids

The invention relates to a multi-step process for the preparation of oxacephems and cephalosporins of the general formula (1) <IMAGE> starting from compounds of the general formula (4) <IMAGE> Original abstract incomplete.

Novel cephalosporin compounds

Novel cephalosporin compounds having antibacterial activity, which are represented by the following general formula (I), wherein R 1 represents an amino group or a protected amino group; Ⓐ represents a 5- or 6-membered heterocyclic ring containing therein 1 to 4 nitrogen, oxygen or sulfur atoms; R 2 represents a normal alkyl group having 1 to 6 carbon atoms, a branched alkyl group having 3 to 6 carbon atoms, an alkoxyalkyl group having 2 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon oms; a cycloalkenyl group having 3 to 6 carbon atoms; an aromatic organic residue; a 3- to 6-membered heterocyclic ring containing 1 to 4 nitrogen, sulfur or oxygen atoms or, wherein Ra and Rb each, which may be the same or different, represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 3 represents an organic residue containing an amino group or a protected amino group and a carboxyl group or a protected carboxyl group; X represents a sulfur atom or an oxygen atom; and R 4 represents a hydrogen atom or a protective group of carboxyl group. The compounds of the general formula (I) described above can also be used as physiologically acceptable addition salts. The compounds exhibit excellent intestinal absorption as well as high blood concentration and longer biological half-life.

METHOD FOR PRODUCING THE NEW DSESQUINATIUM SALTS OF 7BETA- (D- (CARBOXY-4HYDROXYPHENYL) ACETYL) AMINO) -7ALPHA-METHOXY-3-

Cephalosporin derivatives, their preparation and pharmaceutical compositions containing them

Zpusob vyroby (s)-epimeru esteru kyseliny 7beta-malonamido-7alfa-methoxy-3-tetrazolylthiomethyl-1-dethia-1-oxa-3-cefem-4-karboxylove

Patent FR2485017B1

Preparation of 1-oxacephem compound

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

Cephalosporin derivatives.

A cephalosporin derivative of the formula I: < IMAGE > I in which X is < IMAGE > represents one of C-7 acyl groups known in the cephalosporin art, R3 is hydrogen or methoxy, R4 is hydrogen, optionally substituted alkyl or allyl, and R5 is an aromatic heterocyclic ring system which is linked via carbon, and which contains a quaternized nitrogen atom.

PROCESS FOR MANUFACTURING NEW BETALACTAMANTIBIOTICS

Indole derivatives and the prepn.

本发明涉及吲哚衍生物及其一系列的制备方法，以及用含这些新化合物作为有效成分的降低类脂剂。所述吲哚衍生物对于高血脂症和动脉硬化症有治疗和预防作用，对于类脂物代谢异常有很强的改善作用，安全性高，其通式为 式中R、R 1 -R 7 以及A的含意见说明书。

METHOD FOR PRODUCING NEW CEPHALOSPORINE ANALOGS

CEFEM DERIVATIVES AND PROCESS FOR PREPARING THEM.

Epimerization of malonic acid esters