KR20030096222A - 디스타마이신 유도체를 포함하는 항종양 요법 - Google Patents
디스타마이신 유도체를 포함하는 항종양 요법 Download PDFInfo
- Publication number
- KR20030096222A KR20030096222A KR10-2003-7004710A KR20037004710A KR20030096222A KR 20030096222 A KR20030096222 A KR 20030096222A KR 20037004710 A KR20037004710 A KR 20037004710A KR 20030096222 A KR20030096222 A KR 20030096222A
- Authority
- KR
- South Korea
- Prior art keywords
- cancer
- amino
- methyl
- acid
- pyrrole
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- UPBAOYRENQEPJO-UHFFFAOYSA-N n-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide Chemical class CN1C=C(NC=O)C=C1C(=O)NC1=CN(C)C(C(=O)NC2=CN(C)C(C(=O)NCCC(N)=N)=C2)=C1 UPBAOYRENQEPJO-UHFFFAOYSA-N 0.000 title description 8
- 230000000259 anti-tumor effect Effects 0.000 title description 5
- 238000002560 therapeutic procedure Methods 0.000 title description 5
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 238000001990 intravenous administration Methods 0.000 claims abstract description 10
- 241000124008 Mammalia Species 0.000 claims abstract description 5
- -1 5-{[(5-{[(5-{[(2-{[amino (imino) methyl] amino } Ethyl) amino] carbonyl} -1-methyl-1H-pyrrole-3-yl) amino] carbonyl} -1-methyl-1H-pyrrole-3-yl) amino] carbonyl} -1-methyl-1H -Pyrrole-3-yl Chemical group 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 16
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 238000001802 infusion Methods 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
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- 230000003442 weekly effect Effects 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
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- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
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- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 2
- FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 claims description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 0.000 claims description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 2
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- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 2
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- 108010092160 Dactinomycin Proteins 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
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- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
본 발명은 α-할로겐-아크릴로일 디스타마이신 유도체 또는 약제학적으로 허용되는 이의 염의 정맥내 투여를 포함하는 투여 일정에 관한 것이다. 상기 투여는 포유동물에서 다양한 종양의 치료를 가능하게 한다.
Description
본 발명은 일반적으로 암 치료 분야에 관한 것이고, 보다 특히, α-브로모- 및 α-클로로-아크릴로일 디스타마이신 유도체의 투여를 포함하는 항종양 요법에 관한 것이다.
디스타마이신 A는 폴리피롤 구조를 갖는 항바이러스 및 항원충 활성을 갖는 항생 물질이다[참고문헌: Nature 203: 1064(1964); J. Med. Chem. 32: 774-778 (1989)]. 디스타마이신 유도체로서 짧게 후술되는 디스타마이신 A의 수개의 유사물질은 항종양 요법에서 유용한 세포독성 제제로서 당해 분야에 공지되어 있다. 본원에 참조로서 인용된, 본 출원인 명의의 국제 특허원 WO 98/04524는 아크릴로일 디스타마이신 유도체를 기재하고 있고, 여기서, 디스타마이신의 아미디노 잔기는 임의로 질소-함유 말단 그룹, 예를 들어, 시안아미디노, N-메틸아미디노, 구아니디노, 카바모일, 아미독심, 시아노 등으로 치환된다.
항종양 요법에 사용되는 상기 α-할로겐-아크릴로일-디스타마이신 유도체를 포함하는 약제가 본원에 제공되고, 상기 약제는 편의상 효과적인 종양 치료를 할 수 있는 특정 투여 및 섭식 일정에 따라 투여된다.
따라서, 본 발명의 첫번째 목적은 약 0.85㎎/체표면적m2내지 약 20㎎/체표면적m2의 양으로 3주 또는 4주마다 단일 투여로서, 또는 약 0.3㎎/m2/주 내지 약 7㎎/m2/주의 양으로 4주 또는 5주마다 3주 연속으로 매주 약제의 정맥내 주입을 포함하는 일정에 의한 종양 치료용 약제 제조에서 화학식 I의 α-할로겐-아크릴로일 디스타마이신 유도체 또는 약제학적으로 허용되는 이의 염의 용도이다.
상기식에서,
R은 브롬 또는 염소 원자이다.
본 발명은 이의 범위내에 개별적 또는 혼합물 모두로 간주되는 화학식 I의 화합물에 포함되는 모든 가능한 이성체 뿐만 아니라 대사산물 및 화학식 I의 화합물의, 달리 프로드럭으로서 공지된, 약제학적으로 허용되는 생체-전구물질의 용도를 포함한다.
화학식 I의 약제학적으로 허용되는 염은 예를 들어, 염화수소산, 브롬화수소산, 황산, 질산, 아세트산, 프로피온산, 석신산, 말론산, 시트르산, 타르타르산, 메탄설폰산, p-톨루엔설폰산 등과 같은 약제학적으로 허용되는 무기 또는 유기산염이다.
바람직하게는 염화수소산과의 임의로 약제학적으로 허용되는 염의 형태인, 본 발명에 따르는 화학식 I의 화합물의 구체적 예는:
N-(5-{[(5-{[(5-{[(2-{[아미노(이미노)메틸]아미노}에틸)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)-4-[(2-브로모아크릴로일)아미노]-1-메틸-1H-피롤-2-카복사미드 하이드로클로라이드(국제 코드 PNU 166196); 및
N-(5-{[(5-{[(5-{[(2-{[아미노(이미노)메틸]아미노}에틸)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)-4-[(2-클로로아크릴로일)아미노]-1-메틸-1H-피롤-2-카복사미드 하이드로클로라이드이다.
본 발명의 바람직한 양태에 따라서, R이 브롬 원자인 화학식 I의 화합물, 즉, 상기 PNU 166196으로서 제시된 화학식 I의 화합물의 용도가 본원에 제공된다.
상기 화합물은 공지되거나, 예를 들어, 본원에 참조로서 인용된 상기 언급된 국제 특허원 WO 98/04524에서 보고된 바와 같이 공지된 방법에 따라서 용이하게 제조된다.
본 발명의 추가의 양태는 종양으로 고생하는 포유동물에게 약 0.85㎎/체표면적m2내지 약 20㎎/체표면적m2의 양으로 3주 또는 4주마다 단일 투여로서, 또는 약 0.3㎎/m2/주 내지 약 7㎎/m2/주의 양으로 4주 또는 5주마다 3주 연속으로 매주 화학식 I의 디스타마이신 유도체의 정맥내 주입을 포함하여, 사람을 포함하는 상기 포유동물을 치료하는 방법을 제공하는 것이다.
정확한 투여량 범위는 예를 들어, 치료될 환자의 연령, 체중 및 상태를 포함하는 수개의 인자에 따라 확실하게 달라질 것이다. 화학식 I의 디스타마이신 유도체는 바람직하게는 예를 들어 약 10분내 정맥내 주입으로서, 및 프로그램될 수 있는 연속 주입 펌프 또는 정맥내 주입 백을 사용함으로써 투여된다.
본 투여 섭식은 고형 종양, 예를 들어, 위장 종양(예: 결장직장암, 위-식도암, 간암 및 담도암 및 췌장암); 전립선암; 고환암; 폐암; 유방암; 악성 흑색종; 난소암; 자궁경부암을 포함하는 자궁암; 두경부암; 방광암; 육종 및 골육종; AIDS-관련 카포시(Kaposi) 육종을 포함하는 카포시 육종; 신암종; AIDS-관련 림프종을 포함하는 백혈병 및 림프종과 같은 조혈 악성 종양을 포함하는 다양한 종양에 대해 특히 효과적이다.
상기 언급된 바와 같이, 화학식 I의 화합물은 종양 치료에 사용하기 위한 약제학적 조성물의 형태로 약제 제조에 사용된다.
약제학적 조성물은 하나 이상의 약제학적으로 허용되는 담체 및/또는 부형제와 함께, 활성 성분으로서 유효량의 화학식 I의 화합물을 함유할 수 있고, 일반적으로 당해 분야에 공지된 하기 통상적인 방법으로 제조된다.
예로서, 정맥내 주사 또는 주입용 용액제는 담체로서 멸균수를 함유할 수 있거나, 바람직하게는 멸균 등장 식염수의 형태일 수 있다.
또한, 화학식 I의 화합물은 사용전에 재구성되는 적당량의 활성 성분을 함유하는 주사용 동결-건조된 산제 단위로서 제공될 수 있다.
추가로, 화학식 I의 화합물 또는 약제학적으로 허용되는 이의 염은 항종양 요법에서 임의로 다른 항종양제와 함께 동시, 개별적 또는 순차적 사용을 위한 배합된 제제로서 상기 지시된 치료 일정에 따라 투여될 수 있다.
상기 부가적 항종양제는 예를 들어, 알킬화제, 토포이소머라제 I 및 II 억제제, 항미세관 제제 및 항대사물질을 포함한다.
예로서, 특이적 항종양제는 멜팔란, 클로람부실, 메클로레타민, 사이클로포스파미드, 이포스파미드 및 부설판과 같은 머스타드; 카무스틴, 로무스틴, 세무스틴 및 포테무스틴과 같은 니트로소우레아; 다카르바진 및 테모졸로마이드와 같은 테트라진; 티오테파 및 미토마이신 C와 같은 아지리딘; 시스플라틴, 카보플라틴, 옥살리플라틴, 네다플라틴 및 로바플라틴과 같은 백금 유도체; CPT-11, 토포테칸, 9-아미노-캄프토테신, 9-니트로-캄프토테신 및 10,11-메틸렌디옥시-캄프토테신과 같은 캄프토테신 유도체; 독소루비신, 다우노루비신, 에피루비신, 네모루비신 및 이다루비신과 같은 안트라사이클린 유도체; 포도필로톡신 화합물 에토포사이드 및 테니포사이드; 미톡산트론 및 로속산트론과 같은 안트라퀴논 유도체; 아마사크린 및 악티노마이신 D와 같은 아크리딘 유도체; 파클릭탁셀 또는 도세탁셀과 같은 탁산; 빈크리스틴, 빈블라스틴, 빈데신, 비노렐빈과 같은 빈카 알칼로이드; 에스트라무스틴; 메토트렉세이트, 트리메트렉세이트, 토무덱스와 같은 안티폴레이트; 5-FU, 플록수리딘, 프토라푸르 및 카페시타빈과 같은 5-플루오로피리미딘; 시타라빈, 아자시티딘 및 겜시타빈과 같은 시티딘 유사물질이다.
본 발명을 예시하고자 하는 목적으로 본 발명을 제한함이 없이 하기 실시예가 본원에 제공된다.
실시예 1
3주마다 단일 투여로서, N-(5-{[(5-{[(5-{[(2-{[아미노(이미노)메틸]아미노}에틸)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)-4-[(2-브로모아크릴로일)아미노]-1-메틸-1H-피롤-2-카복사미드 하이드로클로라이드(국제 코드 PNU 166196)의 정맥내 주입.
고형 종양인 환자에게 3주마다 단일 투여로서 제공된 표제 화합물의 정맥내 투여를 조사하기 위해서 제I상 약리학적 시험을 수행하였다.
개시 투여량 0.85㎎/m2을 3 내지 6명의 일단의 환자에서, 촉진된 계획(100% 투여량 증가; 1명의 환자/투여량 수준)에 이은 통상적인 투여량의 단계적 확대에 의해 초기에 단계적으로 확대시켰다. 11명의 환자가 지금까지 참가하였고, 0.85, 1.7, 3.4, 5.1 및 7.5㎎/m2의 투여량 수준으로 독성에 대해 25 주기를 평가하였다. 위장 육종으로 고생하는 1명의 환자를 5.1㎎/m2의 투여량 수준으로 치료하여 부분적 반응을 수득하였다.
실시예 2
4주마다 연속 3주 동안 주1회 투여되는, N-(5-{[(5-{[(5-{[(2-{[아미노(이미노)메틸]아미노}에틸)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)-4-[(2-브로모아크릴로일)아미노]-1-메틸-1H-피롤-2-카복사미드 하이드로클로라이드(국제 코드 PNU 166196)의 정맥내 주입.
고형 종양인 환자에게 4주마다 연속 3주 동안 주1회 제공되는 표제 화합물의 정맥내 투여를 조사하기 위해서 제I상 약리학적 시험을 수행하였다.
개시 투여량 0.3㎎/m2/주를 3 내지 6명의 일단의 환자에서, 촉진된 계획(100% 투여량 증가; 1명의 환자/투여량 수준)에 이은 통상적인 투여량의 단계적 확대에 의해 초기에 단계적으로 확대시켰다. 6명의 환자가 지금까지 참가하였고, 0.3, 0.6, 1.2, 2.4 및 4.8㎎/m2/주의 투여량 수준으로 독성에 대해 17 주기를 평가하였다.
Claims (10)
- 0.85㎎/체표면적m2내지 20㎎/체표면적m2의 양으로 3주 또는 4주마다 단일 투여로서, 또는 0.3㎎/m2/주 내지 7㎎/m2/주의 양으로 4주 또는 5주마다 연속 3주 동안 매주 약제의 정맥내 주입을 포함하는 일정에 의한 종양 치료용 약제 제조에서 화학식 I의 α-할로겐-아크릴로일 디스타마이신 유도체 또는 약제학적으로 허용되는 이의 염의 용도.화학식 I상기식에서,R은 브롬 또는 염소 원자이다.
- 제1항에 있어서, 화학식 I의 화합물의 약제학적으로 허용되는 염이 예를 들어, 염화수소산, 브롬화수소산, 황산, 질산, 아세트산, 프로피온산, 석신산, 말론산, 시트르산, 타르타르산, 메탄설폰산, p-톨루엔설폰산 등과 같은 약제학적으로 허용되는 무기 또는 유기산과의 염인 용도.
- 제2항에 있어서, 화학식 I의 화합물의 약제학적으로 허용되는 염이 염산염인 용도.
- 제1항에 있어서, 임의로 약제학적으로 허용되는 염의 형태인 화학식 I의 화합물이 N-(5-{[(5-{[(5-{[(2-{[아미노(이미노)메틸]아미노}에틸)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)-4-[(2-브로모아크릴로일)아미노]-1-메틸-1H-피롤-2-카복사미드인 용도.
- 제1항에 있어서, 종양이 결장직장암, 위-식도암, 간암 및 담도암 및 췌장암을 포함하는 위장 종양; 전립선암; 고환암; 폐암; 유방암; 악성 흑색종; 난소암; 자궁경부암을 포함하는 자궁암; 두경부암; 방광암; 육종 및 골육종; AIDS-관련 카포시(Kaposi) 육종을 포함하는 카포시 육종; 신암종; AIDS-관련 림프종을 포함하는 백혈병 및 림프종과 같은 조혈 악성 종양으로 이루어진 그룹으로부터 선택되는 용도.
- 제1항에 있어서, 항암 용법에서 동시, 개별적 또는 순차적 사용을 위한 배합된 제제로서 부가의 항종양제를 추가로 포함하는 용도.
- 제6항에 있어서, 부가의 항종양제가 멜팔란, 클로람부실, 메클로레타민, 사이클로포스파미드, 이포스파미드, 부설판, 카무스틴, 로무스틴, 세무스틴, 포테무스틴, 다카르바진, 테모졸로마이드, 티오테파, 미토마이신 C, 시스플라틴, 카보플라틴, 옥살리플라틴, 네다플라틴, 로바플라틴, 캄프토테신, CPT-11, 토포테칸, 9-아미노-캄프토테신, 9-니트로-캄프토테신, 10,11-메틸렌디옥시-캄프토테신, 독소루비신, 다우노루비신, 에피루비신, 네모루비신, 이다루비신, 에토포사이드, 테니포사이드, 미톡산트론, 로속산트론, 암사크린, 악티노마이신 D, 파클리탁셀, 도세탁셀, 빈크리스틴, 빈블라스틴, 빈데신, 비노렐빈, 에스트라무스틴, 메토트렉세이트, 트리메트렉세이트, 토무덱스, 5-FU, 플록수리딘, 프토라푸르, 카페시타빈, 시타라빈, 아자시티딘 및 겜시타빈, 및 이의 유도체로 이루어진 그룹으로부터 선택되는 용도.
- 0.85㎎/체표면적m2내지 20㎎/체표면적m2의 양으로 3주 또는 4주마다 단일 투여로서, 또는 0.3㎎/m2/주 내지 7㎎/m2/주의 양으로 4주 또는 5주마다 연속 3주 동안 매주 정맥내 주입에 의해 종양으로 고생하는 사람을 포함한 포유동물에게 제1항에 따르는 화학식 I의 디스타마이신 유도체를 투여함을 포함하는, 종양으로 고생하는 사람을 포함하는 포유동물을 치료하는 방법.
- 제8항에 있어서, 임의로 약제학적으로 허용되는 염의 형태인 화학식 I의 디스타마이신 유도체가 N-(5-{[(5-{[(5-{[(2-{[아미노(이미노)메틸]아미노}에틸)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)아미노]카보닐}-1-메틸-1H-피롤-3-일)-4-[(2-브로모아크릴로일)아미노]-1-메틸-1H-피롤-2-카복사미드인 방법.
- 제8항에 있어서, 종양이 결장직장암, 위-식도암, 간암 및 담도암 및 췌장암을 포함하는 위장 종양; 전립선암; 고환암; 폐암; 유방암; 악성 흑색종; 난소암; 자궁경부암을 포함하는 자궁암; 두경부암; 방광암; 육종 및 골육종; AIDS-관련 카포시(Kaposi) 육종을 포함하는 카포시 육종; 신암종; AIDS-관련 림프종을 포함하는 백혈병 및 림프종과 같은 조혈 악성 종양으로 이루어진 그룹으로부터 선택되는 방법.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/676,770 | 2000-10-02 | ||
| US09/676,770 US6576612B1 (en) | 2000-10-02 | 2000-10-02 | Antitumor therapy comprising distamycin derivatives |
| PCT/EP2001/010988 WO2002028389A1 (en) | 2000-10-02 | 2001-09-21 | Antitumor therapy comprising distamycin derivatives |
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| Publication Number | Publication Date |
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| KR20030096222A true KR20030096222A (ko) | 2003-12-24 |
| KR100827560B1 KR100827560B1 (ko) | 2008-05-07 |
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| Country | Link |
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| US (2) | US6576612B1 (ko) |
| EP (1) | EP1345604B1 (ko) |
| JP (1) | JP2004510734A (ko) |
| KR (1) | KR100827560B1 (ko) |
| CN (1) | CN1468099A (ko) |
| AT (1) | ATE339202T1 (ko) |
| AU (2) | AU2162202A (ko) |
| BR (1) | BR0114389A (ko) |
| CA (1) | CA2424116A1 (ko) |
| CZ (1) | CZ299686B6 (ko) |
| DE (1) | DE60123117T2 (ko) |
| EA (1) | EA006295B1 (ko) |
| EE (1) | EE05241B1 (ko) |
| ES (1) | ES2267841T3 (ko) |
| HU (1) | HUP0301247A2 (ko) |
| IL (1) | IL154755A0 (ko) |
| MX (1) | MXPA03002824A (ko) |
| MY (1) | MY134690A (ko) |
| NO (1) | NO20031410L (ko) |
| PE (1) | PE20020487A1 (ko) |
| PL (1) | PL363926A1 (ko) |
| SK (1) | SK5032003A3 (ko) |
| WO (1) | WO2002028389A1 (ko) |
| ZA (1) | ZA200303405B (ko) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0015446D0 (en) * | 2000-06-23 | 2000-08-16 | Pharmacia & Upjohn Spa | Combined therapy against tumors comprising substituted acryloyl distamycin derivates,taxanes and/or antimetabolites |
| GB0015447D0 (en) * | 2000-06-23 | 2000-08-16 | Pharmacia & Upjohn Spa | Combined therapy against tumors comprising substituted acryloyl derivates and alkylating agents |
| US6576612B1 (en) * | 2000-10-02 | 2003-06-10 | Pharmacia Italia S.P.A. | Antitumor therapy comprising distamycin derivatives |
| US20070249651A1 (en) * | 2001-06-20 | 2007-10-25 | Nerviano Medical Sciences S.R.I. | Combined therapy against tumors comprising substituted acryloyl distamycin derivatives and topoisomerase I and II inhibitors |
| US6969592B2 (en) * | 2001-09-26 | 2005-11-29 | Pharmacia Italia S.P.A. | Method for predicting the sensitivity to chemotherapy |
| BR0308976A (pt) * | 2002-04-02 | 2005-01-11 | Pharmacia Italia Spa | Terapia combinada contra tumores compreendendo derivados de acriloil distamicina substituìda e radioterapia |
| WO2004035045A1 (en) * | 2002-10-16 | 2004-04-29 | Pharmacia Italia S.P.A. | Use of substituted acrylolyl distamycin derivatives in combination with demethylating agents, in the treatment of cancer |
| WO2007074176A1 (es) * | 2005-12-27 | 2007-07-05 | Universidad Del Pais Vasco - Euskal Herriko Unibertsitatea (Upv-Ehu) | Nuevos derivados pirrólicos con actividad inhibidora de desacetilasas de histonas |
| MD36Z (ro) * | 2008-12-02 | 2010-01-31 | Василе ЖОВМИР | Metodă de tratament diferenţiat al carcinomului ductal in situ neinvaziv al glandei mamare |
| MD35Z (ro) * | 2008-12-02 | 2010-01-31 | Василе ЖОВМИР | Metodă de apreciere a riscului dezvoltării carcinomului neinvaziv in situ al glandei mamare |
| MD23Z (ro) * | 2008-12-02 | 2010-01-31 | Василе ЖОВМИР | Metodă de tratament diferenţiat al carcinomului lobular in situ neinvaziv al glandei mamare |
| MD24Z (ro) * | 2008-12-02 | 2010-01-31 | Василе ЖОВМИР | Metodă de tratament diferenţiat al carcinomului neinvaziv al glandei mamare |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8906709D0 (en) * | 1989-03-23 | 1989-05-10 | Creighton Andrew M | Acryloyl substituted pyrrole derivatives |
| GB9615692D0 (en) * | 1996-07-25 | 1996-09-04 | Pharmacia Spa | Acryloyl substituted distamycin derivatives, process for preparing them, and their use as antitumor and antiviral agents |
| GB9806689D0 (en) * | 1998-03-27 | 1998-05-27 | Pharmacia & Upjohn Spa | Acryloyl derivatives analogous to distamycin,process for preparing them,and their use as antitumour and antiviral agents |
| GB9928703D0 (en) * | 1999-12-03 | 2000-02-02 | Pharmacia & Upjohn Spa | Acryloyl peptidic derivatives,process for their preparation and their use as antitumour agents |
| US6576612B1 (en) * | 2000-10-02 | 2003-06-10 | Pharmacia Italia S.P.A. | Antitumor therapy comprising distamycin derivatives |
-
2000
- 2000-10-02 US US09/676,770 patent/US6576612B1/en not_active Expired - Lifetime
-
2001
- 2001-09-21 KR KR1020037004710A patent/KR100827560B1/ko not_active Expired - Fee Related
- 2001-09-21 AU AU2162202A patent/AU2162202A/xx active Pending
- 2001-09-21 CA CA002424116A patent/CA2424116A1/en not_active Abandoned
- 2001-09-21 PL PL01363926A patent/PL363926A1/xx not_active Application Discontinuation
- 2001-09-21 DE DE60123117T patent/DE60123117T2/de not_active Expired - Lifetime
- 2001-09-21 CN CNA018167551A patent/CN1468099A/zh active Pending
- 2001-09-21 CZ CZ20030909A patent/CZ299686B6/cs not_active IP Right Cessation
- 2001-09-21 AU AU2002221622A patent/AU2002221622B2/en not_active Ceased
- 2001-09-21 JP JP2002532214A patent/JP2004510734A/ja not_active Withdrawn
- 2001-09-21 US US10/381,272 patent/US7399748B2/en not_active Expired - Fee Related
- 2001-09-21 AT AT01986259T patent/ATE339202T1/de active
- 2001-09-21 IL IL15475501A patent/IL154755A0/xx not_active IP Right Cessation
- 2001-09-21 EE EEP200300129A patent/EE05241B1/xx not_active IP Right Cessation
- 2001-09-21 ES ES01986259T patent/ES2267841T3/es not_active Expired - Lifetime
- 2001-09-21 SK SK503-2003A patent/SK5032003A3/sk unknown
- 2001-09-21 EP EP01986259A patent/EP1345604B1/en not_active Expired - Lifetime
- 2001-09-21 HU HU0301247A patent/HUP0301247A2/hu unknown
- 2001-09-21 BR BR0114389-1A patent/BR0114389A/pt not_active Application Discontinuation
- 2001-09-21 EA EA200300427A patent/EA006295B1/ru not_active IP Right Cessation
- 2001-09-21 WO PCT/EP2001/010988 patent/WO2002028389A1/en active IP Right Grant
- 2001-09-21 MX MXPA03002824A patent/MXPA03002824A/es unknown
- 2001-09-28 PE PE2001000967A patent/PE20020487A1/es not_active Application Discontinuation
- 2001-09-28 MY MYPI20014542A patent/MY134690A/en unknown
-
2003
- 2003-03-27 NO NO20031410A patent/NO20031410L/no not_active Application Discontinuation
- 2003-05-02 ZA ZA200303405A patent/ZA200303405B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CZ2003909A3 (cs) | 2003-08-13 |
| WO2002028389A1 (en) | 2002-04-11 |
| EP1345604A1 (en) | 2003-09-24 |
| NO20031410D0 (no) | 2003-03-27 |
| EE200300129A (et) | 2003-06-16 |
| AU2002221622B2 (en) | 2007-05-17 |
| US7399748B2 (en) | 2008-07-15 |
| CZ299686B6 (cs) | 2008-10-22 |
| EA200300427A1 (ru) | 2003-10-30 |
| NO20031410L (no) | 2003-03-27 |
| EE05241B1 (et) | 2009-12-15 |
| KR100827560B1 (ko) | 2008-05-07 |
| ZA200303405B (en) | 2004-05-03 |
| DE60123117D1 (de) | 2006-10-26 |
| AU2162202A (en) | 2002-04-15 |
| US6576612B1 (en) | 2003-06-10 |
| CA2424116A1 (en) | 2002-04-11 |
| ATE339202T1 (de) | 2006-10-15 |
| US20040006023A1 (en) | 2004-01-08 |
| EP1345604B1 (en) | 2006-09-13 |
| JP2004510734A (ja) | 2004-04-08 |
| SK5032003A3 (en) | 2003-08-05 |
| PE20020487A1 (es) | 2002-05-23 |
| DE60123117T2 (de) | 2007-02-08 |
| MY134690A (en) | 2007-12-31 |
| BR0114389A (pt) | 2004-02-03 |
| HUP0301247A2 (hu) | 2003-09-29 |
| IL154755A0 (en) | 2003-10-31 |
| PL363926A1 (en) | 2004-11-29 |
| ES2267841T3 (es) | 2007-03-16 |
| CN1468099A (zh) | 2004-01-14 |
| MXPA03002824A (es) | 2003-07-14 |
| EA006295B1 (ru) | 2005-10-27 |
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