Pixantrone Dimaleate

그림문자(GHS)

• 그림문자(GHS)

  

• 신호 어

  Danger

• 유해·위험 문구

  H300：삼키면 치명적임

  H310：피부와 접촉하면 치명적임

  H330：흡입하면 치명적임

  H370：장기(또는, 영향을 받은 알려진 모든 장기를 명시)에 손상을 일으킴(노출되어도 특정 표적장기 독성을 일으키지 않는다는 결정적인 노출경로가 있다면 노출경로를 기재)

• 예방조치문구

  P260：분진·흄·가스·미스트·증기·...·스프레이를 흡입하지 마시오.

  P262：눈, 피부, 의복에 묻지 않도록 하시오.

  P264：취급 후에는 손을 철저히 씻으시오.

  P264：취급 후에는 손을 철저히 씻으시오.

  P270：이 제품을 사용할 때에는 먹거나, 마시거나 흡연하지 마시오.

  P271：옥외 또는 환기가 잘 되는 곳에서만 취급하시오.

  P280：보호장갑/보호의/보안경/안면보호구를 착용하시오.

  P284：호흡 보호구를 착용하시오.

  P301+P310：삼켰다면 즉시 의료기관(의사)의 진찰을 받으시오.

  P302+P350：피부에 묻은 경우,비눗물로 부드럽게 씻기

  P304+P340：흡입하면 신선한 공기가 있는 곳으로 옮기고 호흡하기 쉬운 자세로 안정을 취하시오.

  P307+P311：노출된 경우,독성 물질 센터 또는 의사에게 전화하기

  P310：즉시 의료기관(의사)의 진찰을 받으시오. 삼켰다면 즉시 의료기관(의사)의 도움을 받으시오.

  P320：긴급히 (…) 처치를 하시오.

  P321：(…) 처치를 하시오.

  P322：특정 조치(라벨의 … 참조)

  P330：입을 씻어내시오.

  P361：즉시 오염된 의복을 모두 벗을 것

  P363：다시 사용전 오염된 의류는 세척하시오.

  P403+P233：용기는 환기가 잘 되는 곳에 단단히 밀폐하여 저장하시오.

  P405：밀봉하여 저장하시오.

  P501：...에 내용물 / 용기를 폐기 하시오.

Pixantrone Dimaleate 화학적 특성, 용도, 생산

• 개요

  Pixantrone dimaleate was approved by European Medicine Agency (EMA) on May 10, 2012. It was developed and marketed as Pixuvri® by Cell Therapeutics in EU. (CTI Life Sciences).
  Pixantrone dimaleate is a DNA intercalating agent indicated as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive Non-Hodgkin B-cell Lymphomas (NHL).
  Pixuvri® is available as lyophilised powder for infusion, containing 29 mg of free Pixantrone. The recommended dose is 50 mg/m2 of pixantrone on days 1, 8 and 15 of each 28-day cycle for up to 6 cycles.

• 화학적 성질

  Blue Solid

• 출처

  Pixantrone dimaleate, also known as BBR 2778, was first synthesized by Professors Krapcho and Hacker at the University of Vermont. The University of Vermont and the Boehringer Mannheim Italia research center co-identified the in vitro tumor cell cytotoxicity.

• 용도

  Pixantrone is an antineoplastic drug belonging to group of antitumor antibiotics. Pixantrone is an anlogue of Mitoxantrone (M373425) and is just as potent in the treatment of multiple sclerosis with f ewer toxic effects on cardiac tissue. Studies suggest that Pixantrone significantly reduces amyloid beta (A beta(1-42)) neurotoxicity, a mechanism implicated in Alzheimer's disease.

• 제조 방법

  The manufacturing scale synthesis of pixantrone dimaleate relies on several process modifications from the original synthesis reported by Krapcho in 1994. This modified procedure has provided active pharmaceutical ingredient (API) in high purity (>99%) and is acceptable for use in pharmaceutical applications (Scheme 25). Beginning with pyridine 3,4-dicarboxylic acid (129), generation of the corresponding anhydride 130 proceeded in 76% yield upon treatment with refluxing Ac2O. Next, an AlCl3-promoted Friedel–Crafts reaction of 1,4-difluorobenzene (131) with 130 under reflux conditions provided a mixture of nicotinic acid isomers 132a/132b in 84% yield, which were carried directly to the next step. Cyclization with fuming H2SO4 yielded the desired difluorobenzo-isoquinoline-dione core 133, which was further functionalized with ethylenediamine (134) to provide the free base of pixantrone. Subjection of the pixantrone free base to aqueous acetic anhydride and maleic acid provided pixantrone dimaleate (XX) in 92% yield over 3 steps.
  
  Synthesis of pixantrone dimaleate

• 생물학적 활성

  Pixantrone (BBR 2778) is an aza-anthracenedione with enhanced antitumor activity due to its DNA-intercalating and topoisomerase II-poisoning activity. Pixantrone shows no signs of acute or delayed cardiotoxicity seen with anthracyclines mitoxantrone and doxorubicin (DOX), while exhibiting comparable in vivo efficacy against solid tumors in mice. Tests conducted on human myocardial strips ex vivo shows that not only pixantrone does not form superoxide anion and hydrogen peroxide (O2?? and H2O2) seen with DOX due to redox activation, pixantrone and its metabolites, especially N-dealkylated, show competitive inhibition against DOX reduction. While mitoxantrone does not form O2?? and H2O2 on its own, it synergizes with DOX to form more O2?? and H2O2, whose formation and subsequent production of the long-lived metabolite doxorubicinol contribute to DOX cardiotoxicity.

• 참고 문헌

  [1] A. PAUL KRAPCHO. 6,9-Bis[(aminoalkyl)amino]benzo[g]isoquinoline-5,10-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluations[J]. Journal of Medicinal Chemistry, 1994, 37 6: 828-837. DOI:10.1021/jm00032a018.
  [2] 170. Krapcho, A. P.; Hacker, M. P.; Cavalletti, E.; Giuliani, F. C. US Patent 5587382 A,1996.
  [3] Spinelli, S.; Didomenico, R. WO Patent 9526189 A1, 1995.
  [4] Krapcho, P. A. EP Patent 503537 A1, 1992

Pixantrone Dimaleate 준비 용품 및 원자재

Pixantrone Dimaleate 공급 업체

Global(125)Suppliers

Pixantrone Dimaleate 관련 검색