RU2016130095A - Конъюгат анти-trop2 антитело-лекарственное средство - Google Patents
Конъюгат анти-trop2 антитело-лекарственное средство Download PDFInfo
- Publication number
- RU2016130095A RU2016130095A RU2016130095A RU2016130095A RU2016130095A RU 2016130095 A RU2016130095 A RU 2016130095A RU 2016130095 A RU2016130095 A RU 2016130095A RU 2016130095 A RU2016130095 A RU 2016130095A RU 2016130095 A RU2016130095 A RU 2016130095A
- Authority
- RU
- Russia
- Prior art keywords
- cancer
- crystalline form
- benzylcarbamoyl
- pyrazino
- octahydro
- Prior art date
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- VHOZWHQPEJGPCC-ISZZHBKVSA-N [4-[[(6s,9s)-1-(benzylcarbamoyl)-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazin-6-yl]methyl]phenyl] dihydrogen phosphate Chemical compound C([C@@H]1N2C(N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=NC=CC=C2C=CC=1)C)C1=CC=C(OP(O)(O)=O)C=C1 VHOZWHQPEJGPCC-ISZZHBKVSA-N 0.000 claims 4
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 208000032612 Glial tumor Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
- 208000022136 colorectal lymphoma Diseases 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 201000005787 hematologic cancer Diseases 0.000 claims 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 238000001228 spectrum Methods 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 206010046766 uterine cancer Diseases 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
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- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
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- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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Claims (8)
1. Кристаллическая форма 4-(((6S,9S)-1-(бензилкарбамоил)-2,9-диметил-4,7-диоксо-8-(хинолин-8-илметил)октагидро-1H-пиразино[2,1-c][1,2,4]триазин-6-ил)метил)фенилдигидрофосфата или его гидрата.
2. Кристаллическая форма гидрата 4-(((6S,9S)-1-(бензилкарбамоил)-2,9-диметил-4,7-диоксо-8-(хинолин-8-илметил)октагидро-1H-пиразино[2,1-c][1,2,4]триазин-6-ил)метил)фенилдигидрофосфата.
3. Кристаллическая форма по п.2, демонстрирующая дифракционный пик при угле дифракции (2θ±0,2°) 15,9° в порошковой рентгеновской дифракции.
4. Кристаллическая форма гидрата 4-(((6S,9S)-1-(бензилкарбамоил)-2,9-диметил-4,7-диоксо-8-(хинолин-8-илметил)октагидро-1H-пиразино[2,1-c][1,2,4]триазин-6-ил)метил)фенилдигидрофосфата, демонстрирующая пики при химических сдвигах (м.д.) 15,8, 56,4, 127,8, 157,4 и 168,6 в спектре твердотельного 13С ЯМР.
5. Способ получения кристаллической формы 4-(((6S,9S)-1-(бензилкарбамоил)-2,9-диметил-4,7-диоксо-8-(хинолин-8-илметил)октагидро-1H-пиразино[2,1-c][1,2,4]триазин-6-ил)метил)фенилдигидрофосфата или его гидрата, включающий стадию кристаллизации из растворителя, выбранного из группы, состоящей из спиртового растворителя, воды и их комбинации.
6. Фармацевтическая композиция, содержащая кристаллическую форму по любому одному из п.п.1-4 в качестве активного ингредиента.
7. Противоопухолевое средство, содержащее кристаллическую форму по любому одному из п.п.1-4 в качестве активного ингредиента.
8. Противоопухолевое средство по п.7, в котором опухоль представляет собой рак легких, рак молочной железы, рак желудка, рак поджелудочной железы, рак печени, рак матки, рак яичников, глиому, меланому, колоректальный рак, лимфому или рак крови.
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