KR970059176A

KR970059176A - Novel carbapenem derivatives and methods for producing the same

Info

Publication number: KR970059176A
Application number: KR1019960001445A
Authority: KR
Inventors: 문치장; 임성수; 이세종; 우윤희; 장우익; 최문정; 김지연
Original assignee: 서치영; 주식회사 대웅제약
Priority date: 1996-01-24
Filing date: 1996-01-24
Publication date: 1997-08-12

Abstract

본 발명은 구조식(Ⅰ)로 나타내지는 신규한 카바페넴 유도체, 그의 약제학적으로 허용되는 염 및 에스테르, 그들의 제조방법, 그리고 그들을 함유하는 제약학적 조성물을 제공한다.The present invention provides novel carbapenem derivatives represented by Structural Formula (I), pharmaceutically acceptable salts and esters thereof, a process for their preparation, and a pharmaceutical composition containing them.

상기 일반식(I)에서, R₁은 수소원자 또는 메틸기를 나타내고, R₂는 수소원자, 또는 약제학적으로 허용되는 금속, 비금속 염류 또는 적절한 카르복시 보호기를 나타내며, R₃는 수소원자, 또는 아미노 보호기 또는 약제학적으로 허용되는 염을 나타내고, R₄는 일반식(Ⅴ)의 -N-A-R₅를 나타내며, -N-A-는 질소원자 1∼4개를 포함하는 3∼7원환의 헤테로 사이클릭기 또는 질소원자 1∼4개를 포함하는 5∼10원환의 플리아자비이사이클릭기를 나타내고, 상기의 헤테로사이클릭기 또는 플리아자바이사이클릭기는 사이클릭의 아미노기에 수소 또는 저급알칼 또는 아미노기보호기가 결합되어 있으며, R₅는 수소원자 또는 다음의 일반식 -(CH₂)_n-@ (여기에서, n=0∼4의 정수이고, R₆및 R₇은 각각 수소 또는 탄소수 1∼4의 저급알킬 또는 아미노기 보호기를 나타낸다)의 그룹이다.Wherein R ₁ represents a hydrogen atom or a methyl group and R ₂ represents a hydrogen atom or a pharmaceutically acceptable metal, a nonmetal salt or an appropriate carboxy protecting group, R ₃ represents a hydrogen atom or an amino-protecting group Or a pharmaceutically acceptable salt thereof, R ₄ represents -NAR ₅ of the formula (V), -NA- represents a 3- to 7-membered heterocyclic group containing 1 to 4 nitrogen atoms or a nitrogen atom Wherein the heterocyclic group or the fl iazabicyclic group is a cyclic amino group having a hydrogen or a lower alkyl or amino group protecting group attached thereto and R ₅ represents a hydrogen atom or a group represented by the following general formula - (CH ₂ ) _n - (wherein n is an integer of 0 to 4, R ₆ and R ₇ each represent hydrogen or a lower alkyl group having 1 to 4 carbon atoms, ) Of A group.

Description

Novel carbapenem derivatives and methods for producing the same

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음Since this is a trivial issue, I did not include the contents of the text.

Claims

A novel carbapenem derivative represented by the following structural formula (I), a pharmaceutically acceptable salt and ester thereof.

Wherein R ₁ represents a hydrogen atom or a methyl group and R ₂ represents a hydrogen atom or a pharmaceutically acceptable metal, a nonmetal salt or an appropriate carboxy protecting group, R ₃ represents a hydrogen atom or an amino-protecting group Or a pharmaceutically acceptable salt thereof, wherein R ₄ represents -N-1-R ₅ of the formula (V), -NA- represents a 3-7 membered heterocyclic ring containing 1-4 nitrogen atoms Or a 5- to 10-membered ring-containing polyazabicyclic group containing 1-4 nitrogen atoms, and the above-mentioned heterocyclic group or polyarabazacyclic group is a cyclic amino group hydrogen or lower alkyl or amino-protecting group, R ₅ is a hydrogen atom or a group represented by the following general formula (Wherein n = 0 to 4 are integers and R ₆ and R ₇ each represent hydrogen or a lower alkenyl group having 1 to 4 carbon atoms).

The compound of formula (I) according to claim 1, wherein R ₁ is a methyl group, R ₂ is a hydrogen atom and R ₃ and R ₄ are as defined in claim 1, And salts thereof.

The compound of general formula (I) according to claim 1, wherein R ₁ is a methyl group, R ₂ and R ₃ are each a hydrogen atom, and R ₄ is as defined in claim 1, Acceptable salts and esters.

The compound of general formula (I) according to claim ₁ , wherein R ₁ , R ₂ and R ₃ are each a hydrogen atom and R ₄ is as defined in claim ₁ , a pharmaceutically acceptable salt thereof And esters.

2. The compound according to claim 1, wherein the stereochemical configuration is (5R, 6S, 8R, 2S, 4R) or (1R, 5S, 6S, 8R, 2'S, 4'R) I), the pharmaceutically acceptable salts and esters thereof.

2. The compound according to claim 1, which is (1R, 5S, 6S), 6 - [(R) -1-hydroxyethyl] (I), which is a pharmaceutically acceptable salt thereof, wherein R < 1 > Salts and esters.

2. The compound according to claim 1, which is (1R, 5S, 6S) 6 - [(R) -1-hydroxyethyl] (I), which is a pharmaceutically acceptable salt thereof, wherein R < 1 > is methyl, R < 1 > And esters.

2. The compound according to claim 1, which is (1R, 5S, 6S) 6 - [(R) -1-hydroxyethyl] Diazabicyclo [3.3.0] octane-3-ylsulfonyl) -1-hydroxyethyl] pyrrolidin-4-ylthio] -1-carbapen- I), the pharmaceutically acceptable salts and esters thereof.

2. The compound according to claim 1, which is (1R, 5S, 6S) 6 - [(R) -1-hydroxyethyl] Diisabicyclo [3.3.0] octane- (15) -en-3-ylsulfonyl] -1-hydroxyethyl] pyrrolidin-4-ylthio] -1-carbapen- Compounds of general formula (I) which are carboxylic acids, their pharmaceutically acceptable salts and esters.

2. The compound according to claim 1, which is (1R, 5S, 6S) -6- [(R) -1-hydroxyethyl] -Diazabicyclo [3.3.0] octane-7-ylsulfonyl) -1-hydroxyethyl] pyrrolidin-4-ylthio] And pharmaceutically acceptable salts and esters thereof.

2. The compound according to claim 1, which is (1R, 5S, 6S) -6- [(R) -1-hydroxyethyl] 2-yl) sulfonyl] -1-hydroxyethyl] pyrrolidin-4-ylthio] -1-carbapen- 2- Compounds of general formula (I) which are the compounds of the formula (I), their pharmaceutically acceptable salts and esters.

2. The compound according to claim 1, which is (1R, 5S, 6S) -6- [(R) -1- (I) wherein R < 1 > is heptane-2-ylsulfonyl) -1-hydroxyethyl] pyrrolidin-4-ylthio] Pharmaceutically acceptable salts and esters.

2. The compound according to claim 1, which is (1R, 5S, 6S) -6- [(R) -1-hydroxyethyl] (I) wherein R < 1 > is methyl, R < 1 > Pharmaceutically acceptable salts and esters.

2. The compound according to claim 1, which is (1R, 5S, 6S) -6- [(R) -1- (I) wherein R < 1 > is methyl, R < 1 > Salts and esters.

Characterized in that a compound represented by the following general formula (VIII) is reacted with a compound represented by the following general formula (IX) to obtain a compound represented by the following general formula (X) and, if necessary, a protecting group is removed from the compound represented by the general formula Lt; RTI ID = 0.0 > (I) < / RTI >

Wherein R ₁ represents a hydrogen atom or a methyl group and R ₂ represents a hydrogen atom or a pharmaceutically acceptable metal, a nonmetal salt or a suitable carboxy protecting group, R ₃ represents a hydrogen atom, an amino-protecting group or a pharmaceutically acceptable salt thereof R ₄ represents -NAR ₅ of the formula (V), -NA- represents a 3- to 7-membered heterocyclic group containing 1 to 4 nitrogen atoms or 1 to 4 nitrogen atoms A 5- to 10-membered ring represents a polyazabisyl isocyanate group, R ₅ represents a hydrogen atom or a group represented by the following formula (Wherein n is an integer from 0 to 4, and R ₆ and R ₇ each represent hydrogen or a lower alkenyl group having 1 to 4 carbon atoms). R ₈ represents a hydrogen atom or a hydroxy-protecting group.

A biodegradable composition comprising the compound of claim 1 as an active ingredient together with a physiologically acceptable carrier.

※ Note: It is disclosed by the contents of the first application.