CN112020495B - N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1h-吡唑-3-磺酰胺钠盐 - Google Patents
N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1h-吡唑-3-磺酰胺钠盐 Download PDFInfo
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Abstract
本发明涉及一种N‑((1,2,3,5,6,7‑六氢‑对称引达省‑4‑基)氨基甲酰基)‑1‑异丙基‑1H‑吡唑‑3‑磺酰胺钠盐以及其水合物、溶剂化物和多晶型形式。本发明进一步涉及包含这种化合物的药物组合物以及这种化合物在治疗和预防医学病症和疾病中的用途，最尤其是在通过NLRP3抑制来治疗和预防医学病症和疾病中的用途。
Description
技术领域
本发明涉及一种N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐以及其水合物、溶剂化物和多晶型形式。本发明进一步涉及包含这种化合物的药物组合物以及这种化合物在治疗和预防医学病症和疾病中的用途，最尤其是在通过NLRP3抑制来治疗和预防医学病症和疾病中的用途。
背景技术
NOD样受体(NLR)家族、含热蛋白结构域的蛋白3(pyrin domain-containingprotein 3；NLRP3)炎症体(inflammasome)为炎症过程的组件，且其异常的活性在遗传性病症诸如冷吡啉相关周期性综合征(cryopyrin-associated periodic syndrome；CAPS)和复杂疾病诸如多发性硬化、2型糖尿病、阿尔茨海默氏病(Alzheimer's disease)和动脉粥样硬化中具有致病性。
NLRP3为感测许多病原体衍生因子、环境因子和宿主衍生因子的细胞内信号传导分子。在活化时，NLRP3结合含有半胱氨酸天冬氨酸蛋白酶活化和募集结构域的凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a caspaseactivation and recruitment domain；ASC)。然后ASC聚合以形成被称为ASC斑点的大型聚集体。聚合的ASC继而与半胱胺酸蛋白酶半胱氨酸天冬氨酸蛋白酶-1相互作用以形成被称为炎症体的复合物。这样导致半胱氨酸天冬氨酸蛋白酶-1的活化，半胱氨酸天冬氨酸蛋白酶-1裂解促炎症细胞因子IL-1β和IL-18的前体形式(分别称为pro-IL-1β和pro-IL-18)从而将这些细胞因子活化。半胱氨酸天冬氨酸蛋白酶-1还介导被称为细胞焦亡(pyroptosis)的一类炎症性细胞死亡。ASC斑点还可募集并活化半胱氨酸天冬氨酸蛋白酶-8，其可加工pro-IL-1β和pro-IL-18并触发凋亡性细胞死亡。
半胱氨酸天冬氨酸蛋白酶-1将pro-IL-1β和pro-IL-18裂解成其活性形式，这些活性形式被分泌出细胞。活性半胱氨酸天冬氨酸蛋白酶-1还裂解消皮素-D(gasdermin-D)以触发细胞焦亡。尽管其控制细胞焦亡性细胞死亡途径，但是半胱氨酸天冬氨酸蛋白酶-1还介导警报素分子诸如IL-33和高迁移率族蛋白1(high mobility group box 1protein；HMGB1)的释放。半胱氨酸天冬氨酸蛋白酶-1还裂解细胞内IL-1R2，导致其降解并允许IL-1α的释放。在人细胞中，半胱氨酸天冬氨酸蛋白酶-1还可控制IL-37的加工和分泌。许多其他半胱氨酸天冬氨酸蛋白酶-1底物诸如细胞骨架和糖解途径的组件可导致半胱氨酸天冬氨酸蛋白酶-1依赖性炎症。
NLRP3依赖性ASC斑点被释放至细胞外环境中，在细胞外环境中其可活化半胱氨酸天冬氨酸蛋白酶-1，诱导半胱氨酸天冬氨酸蛋白酶-1底物的加工，且传播炎症。
衍生自NLRP3炎症体活化的活性细胞因子为炎症的重要驱使因子(driver)且与其他细胞因子途径相互作用以成形对感染和损伤的免疫应答。例如，IL-1β信号传导诱导促炎症细胞因子IL-6和TNF的分泌。IL-1β和IL-18与IL-23协同诱导由记忆CD4 Th17细胞和由γδT细胞在不存在T细胞受体接合的情况下的IL-17产生。IL-18和IL-12还协同以诱导由驱使Th1应答的记忆T细胞和NK细胞的IFN-γ产生。
遗传性CAPS疾病穆克尔-韦尔斯综合征(Muckle–Wells syndrome；MWS)、家族性冷因性自身炎症性综合征(FCAS)和新生儿发病多系统炎症性疾病(neonatal-onsetmultisystem inflammatory disease；NOMID)是由NLRP3中的功能获得型突变引起的，因此将NLRP3定义为炎症过程的关键组件。NLRP3还牵涉许多复杂性疾病的发病机理，特别包括诸如2型糖尿病、动脉粥样硬化、肥胖和痛风的代谢病症。
NLRP3在中枢神经系统疾病中的作用正在浮现，且已显示肺部疾病受NLRP3影响。此外，NLRP3在肝部疾病、肾部疾病和老化的发展中起作用。这些关联中的许多关联是使用Nlrp3-/-小鼠定义的，但也有对这些疾病中NLRP3的特异性活化的了解。在2型糖尿病(T2D)中，胰脏中胰岛淀粉样多肽的沉积活化NLRP3和IL-1β信号传导，导致细胞死亡和炎症。
已显示若干小分子抑制NLRP3炎症体。格列本脲(glyburide)在微摩尔浓度下应答于NLRP3而不是NLRC4或NLRP1的活化抑制IL-1β产生。其他先前已表征的弱NLRP3抑制剂包括小白菊内酯(parthenolide)、3,4-亚甲基二氧-β-硝苯乙烯和二甲亚砜(DMSO)，但是这些剂的效力有限且具有非特异性。
目前对于NLRP3相关疾病的治疗包括靶向IL-1的生物剂。这些为重组IL-1受体拮抗剂阿那白滞素(anakinra)、中和IL-1β抗体卡那单抗(canakinumab)和可溶性诱饵IL-1受体利纳西普(rilonacept)。这些方法已证明在CAPS的治疗中是成功的，且这些生物剂已用于其他IL-1β相关疾病的临床试验。
一些含有二芳基磺酰基脲的化合物已被鉴别为细胞因子释放抑制药(CRID)(Perregaux等人,J.Pharmacol.Exp.Ther.299,187-197,2001)。CRID为一类含有二芳基磺酰基脲的化合物，其抑制IL-1β的翻译后加工。IL-1β的翻译后加工伴随着半胱氨酸天冬氨酸蛋白酶-1的活化和细胞死亡。CRID阻止活化的单核细胞，使得半胱氨酸天冬氨酸蛋白酶-1保持非活性且保留质膜潜伏。
某些含有磺酰脲之化合物同样被公开为NLRP3抑制剂(参见例如，Baldwin等人,J.Med.Chem.,59(5),1691-1710,2016；以及WO 2016/131098 A1、WO 2017/129897 A1、WO2017/140778 A1、WO 2017/184604 A1、WO 2017/184623 A1、WO 2017/184624 A1和WO2018/015445 A1)。WO 2016/131098 A1公开了N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺。
需要提供具有改善的药理学和/或生理学和/或生理化学性质的化合物和/或提供已知化合物的可用替代的化合物。
发明内容
本发明的第一方面提供了一种N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或者其水合物或溶剂化物。
本发明的第二方面提供了一种N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或者其水合物或溶剂化物的多晶型形式。
在某些实施方案中，第二方面的多晶型形式为N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物的多晶型物。此类多晶型物的实例包括在本文中称为形式1的多晶型物。
在某些实施方案中，第二方面的多晶型形式为N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐无水物的多晶型物。此类多晶型物的实例包括在本文中称为形式2的多晶型物。
本发明的第三方面提供了一种用于制备N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐的方法，其包括：
(a)在存在一种或多种极性溶剂的情况下，将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸和钠离子源接触以形成混合物；以及
(b)从所述混合物获得固体的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐。
本发明的第四方面提供了一种药物组合物，其包含本发明的第一方面的盐、水合物或溶剂化物或者本发明的第二方面的多晶型形式和药学上可接受的赋形剂。
本发明的其他方面提供了治疗或预防疾病、病症或病况的医学用途和方法，最尤其是通过NLRP3抑制来治疗或预防疾病、病症或病况的医学用途和方法。
附图说明
图1显示实施例2的盐的XRPD分析。
图2显示实施例2的盐的TGA和DSC分析。
图3显示实施例3的盐的XRPD分析。
图4显示实施例3的盐的TGA和DSC分析。
具体实施方式
活性药物化合物的盐形式之间的差异可能对化合物的固体形式的性质有深远的影响。例如，与非盐化化合物和同一化合物的其他盐形式相比，物质的固体形式的结晶度、溶解度、固有溶解速率、在储存下的稳定性以及在水性介质中的稳定性都产生差异。本发明的盐提供了N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺的形式，并且特别是钠盐，其具有某些优于其他盐并且优于其游离酸的优点。
本发明的第一方面提供了一种N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或者其水合物或溶剂化物。N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺(还称为游离酸)具有式：
本发明的第一方面的盐涵盖具有任意比率的游离酸与钠离子的共轭碱的盐，例如单钠盐、二钠盐和半钠盐。在一个实施方案中，N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐为单钠盐。
本发明第一方面的盐可为无水的或为水合物(例如，半水合物、一水合物、二水合物或三水合物)或其他溶剂化物的形式。此类溶剂化物可用常见有机溶剂(包括但不限于醇溶剂，例如甲醇、乙醇或异丙醇)形成。在一个实施方案中，N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐为一水合物或无水物。在一个实施方案中，N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐为一水合物。
本发明的第一方面的盐、水合物和溶剂化物可为任何结晶或非晶形式，或者可以呈结晶和非晶形式的任何混合物而存在。在本发明的第一方面的盐、水合物和/或溶剂化物呈结晶形式和非晶形式的混合物而存在的实施方案中，所述盐、水合物和/或溶剂化物可具有结晶度。如本文所用，结晶度为以一种或多种结晶形式的本发明的第一方面的盐、水合物和/或溶剂化物的重量百分比，表述为盐、水合物和/或溶剂化物总重量的百分比。
本发明的第一方面的盐、水合物和溶剂化物的结晶度优选为50％或更多(例如，60％或更多、70％或更多、80％或更多、90％或更多、95％或更多或99％或更多)。更优选地，本发明的第一方面的盐、水合物和溶剂化物为结晶。如本文所用，如果本发明的第一方面的盐、水合物和/或溶剂化物的结晶度为90％或更多(例如，95％或更多或99％或更多)，那么它们通常被称为结晶。
在一个实施方案中，N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐为结晶的。在一个实施方案中，N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐为结晶的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物。
本发明的第一方面的结晶盐、水合物和/或溶剂化物可以一种或多种多晶型形式存在。多晶型是指固体物质以一种或多种不同的晶体结构中(即，在晶格中具有一种或多种相对于彼此不同的分子排列)存在的能力。物质的不同多晶型物可具有不同的物理性质，诸如溶解度、固有溶解速率和量热行为(例如，熔点)。不同多晶型物还可以表现出稳定性差异(例如，相对于转化成其他结晶或非晶形式的稳定性差异)。活性药物成分的物理性质可能影响药物产品安全性能和功效。因此，有利的是鉴别出具有药学上可接受的性质的药物物质的多晶型形式。
因此，本发明的第二方面提供了一种N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或者其水合物或溶剂化物的多晶型形式。
本发明的第一方面的盐、水合物和溶剂化物以及本发明的第二方面的多晶型形式可含有：任何稳定的同位素，包括但不限于12C、13C、1H、2H(D)、14N、15N、16O、17O、18O、19F和127I；以及任何放射性同位素，包括但不限于11C、14C、3H(T)、13N、15O、18F、123I、124I、125I和131I。
在某些实施方案中，第二方面的多晶型形式为N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物的多晶型物。此类多晶型物的实例包括在本文中称为形式1的多晶型物。
形式1多晶型物可以通过包括X射线粉末衍射(XRPD)、差示扫描量热法(DSC)和/或热重分析(TGA)的技术来表征。
如本文所用，XRPD数据通常为可在20℃下使用CuKα辐射获得的数据。如本文所用，当结合XRPD峰的位置使用时，“近似(approximate或approximately)”通常指所说明位置±0.2°2θ。
形式1多晶型物的XRPD光谱包括在近似以下处的峰：4.3°2θ、8.7°2θ和20.6°2θ。更通常，形式1多晶型物的XRPD光谱包括在近似以下处的峰：4.3°2θ、7.3°2θ、8.7°2θ、16.5°2θ和20.6°2θ。更通常，形式1多晶型物的XRPD光谱包括在近似以下处的峰：4.3°2θ、6.7°2θ、7.3°2θ、8.7°2θ、15.8°2θ、16.5°2θ和20.6°2θ。还通常，形式1多晶型物的XRPD光谱包括在近似以下处的峰：4.3°2θ、6.7°2θ、7.3°2θ、8.7°2θ、9.0°2θ、15.8°2θ、16.5°2θ、18.0°2θ和20.6°2θ。
通常，形式1多晶型物的XRPD光谱中的10个最强峰包括5个或更多个(例如，6个或更多个、7个或更多个、8个或更多个、9个或更多个或10个)具有选自以下的近似2θ值的峰：4.3°2θ、6.2°2θ、6.7°2θ、7.3°2θ、8.7°2θ、9.0°2θ、12.1°2θ、15.8°2θ、16.5°2θ、18.0°2θ、18.1°2θ、20.6°2θ、21.6°2θ和24.5°2θ。更通常，形式1多晶型物的XRPD光谱中的10个最强峰包括5个或更多个(例如，6个或更多个、7个或更多个、8个或更多个、9个或更多个或10个)具有选自以下的近似2θ值的峰：4.3°2θ、6.2°2θ、6.7°2θ、7.3°2θ、8.7°2θ、9.0°2θ、12.1°2θ、15.8°2θ、16.5°2θ、18.0°2θ、20.6°2θ和21.6°2θ。更通常，形式1多晶型物的XRPD光谱中的10个最强峰包括5个或更多个(例如，6个或更多个、7个或更多个、8个或更多个、9个或更多个或10个)具有选自以下的近似2θ值的峰：4.3°2θ、6.2°2θ、6.7°2θ、7.3°2θ、8.7°2θ、9.0°2θ、15.8°2θ、16.5°2θ、18.0°2θ和20.6°2θ。
形式1多晶型物的XRPD光谱近似如以下表1中所示：
表1
通常，形式1多晶型物的TGA特征图包括在20℃与100℃之间约4.6％至约5.0％的重量损失(例如，约4.7％至约4.9％的重量损失或约4.8％的重量损失)。
通常，形式1多晶型物的DSC特征图包括第一吸热和第二吸热。形式1多晶型物的第一吸热通常在41℃至约45℃范围内的温度(例如，在约42℃至约44℃范围内的温度或者约43℃的温度)下开始。形式1多晶型物的第一吸热通常在72℃至约76℃范围内的温度(例如，在约73℃至约75℃范围内的温度或者约74℃的温度)下具有峰。通常，形式1多晶型物的第一吸热的焓变为约69J/g至约73J/g(例如，约70J/g至约72J/g或约71J/g)。形式1多晶型物的第二吸热通常在177℃至约181℃范围内的温度(例如，在约178℃至约180℃范围内的温度或者约179℃的温度)下开始。形式1多晶型物的第二吸热通常在188℃至约192℃范围内的温度(例如，在约189℃至约191℃范围内的温度或者约190℃的温度)下具有峰。通常，形式1多晶型物的第二吸热的焓变为约13J/g至约17J/g(例如，约14J/g至约16J/g或约15J/g)。
形式1多晶型物可通过以下方法获得，包括：
(a)在存在水和任选地极性非质子有机溶剂的情况下，将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸和钠离子源接触以形成溶液；或将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐溶解于包含水和任选地极性非质子有机溶剂的溶剂混合物中以形成溶液；以及
(b)从所述溶液获得呈形式1多晶型物的结晶N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物。
在优选实施方案中，步骤(a)中所用的溶剂混合物包含水和极性非质子有机溶剂。在优选实施方案中，极性非质子有机溶剂为丙酮。水与极性非质子有机溶剂的体积比通常为1:35至1:1(例如，1:20至1:1、或1:15至1:4、或1:13至1:6、或1:11至1:8或约1:9)。在优选实施方案中，用水和极性非质子有机溶剂的溶剂混合物处理N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸，接着添加钠离子源，以形成溶液。
在优选实施方案中，在步骤(b)中，结晶N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物形式1多晶型物可由所述溶液通过添加合适的反溶剂，或者通过组合地添加合适的反溶剂并且添加晶种来获得。优选的反溶剂为乙醚、二异丙醚和叔丁基甲醚。特别优选的为叔丁基甲醚。
用于获得形式1多晶型物的另外优选的方法包括极性非质子有机溶剂、钠离子源、获得固体钠盐的手段和方法的其他特征均如本文关于本发明的第三方面的方法所述的方法。
在某些实施方案中，第二方面的多晶型形式为N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐无水物的多晶型物。此类多晶型物的实例包括在本文中称为形式2的多晶型物。
形式2多晶型物的XRPD光谱包括在近似以下处的峰：5.1°2θ、21.7°2θ和22.7°2θ。更通常，形式2多晶型物的XRPD光谱包括在近似以下处的峰：5.1°2θ、17.9°2θ、18.7°2θ、21.7°2θ和22.7°2θ。更通常，形式2多晶型物的XRPD光谱包括在近似以下处的峰：5.1°2θ、17.1°2θ、17.9°2θ、18.7°2θ、20.1°2θ、21.7°2θ和22.7°2θ。还通常，形式2多晶型物的XRPD光谱包括在近似以下处的峰：5.1°2θ、8.9°2θ、17.1°2θ、17.9°2θ、18.7°2θ、20.1°2θ,20.6°2θ、21.7°2θ和22.7°2θ。
通常，形式2多晶型物的XRPD光谱中的10个最强峰包括5个或更多个(例如，6个或更多个、7个或更多个、8个或更多个、9个或更多个或10个)具有选自以下的近似2θ值的峰：5.1°2θ、6.6°2θ、7.7°2θ、8.9°2θ、9.3°2θ、10.3°2θ、16.2°2θ、17.1°2θ、17.9°2θ、18.7°2θ、20.1°2θ、20.6°2θ、21.7°2θ和22.7°2θ。更通常，形式2多晶型物的XRPD光谱中的10个最强峰包括5个或更多个(例如，6个或更多个、7个或更多个、8个或更多个、9个或更多个或10个)具有选自以下的近似2θ值的峰：5.1°2θ、6.6°2θ、8.9°2θ、10.3°2θ、16.2°2θ、17.1°2θ、17.9°2θ、18.7°2θ、20.1°2θ、20.6°2θ、21.7°2θ和22.7°2θ。更通常，形式2多晶型物的XRPD光谱中的10个最强峰包括5个或更多个(例如，6个或更多个、7个或更多个、8个或更多个、9个或更多个或10个)具有选自以下的近似2θ值的峰：5.1°2θ、8.9°2θ、16.2°2θ、17.1°2θ、17.9°2θ、18.7°2θ、20.1°2θ、20.6°2θ、21.7°2θ和22.7°2θ。
形式2多晶型物的XRPD光谱近似如以下表2中所示：
表2
通常，形式2多晶型物的TGA特征图包括在20℃与160℃之间约8.5％至约8.9％的重量损失(例如，约8.6％至约8.8％的重量损失或约8.7％的重量损失)。
通常，形式2多晶型物的DSC特征图包括第一吸热、第二吸热和第三吸热。形式2多晶型物的第一吸热通常在61℃至约65℃范围内的温度(例如，在约62℃至约64℃范围内的温度或者约63℃的温度)下开始。形式2多晶型物的第一吸热通常在73℃至约77℃范围内的温度(例如，在约74℃至约76℃范围内的温度或者约75℃的温度)下具有峰。通常，形式2多晶型物的第一吸热的焓变为约1J/g至约5J/g(例如，约2J/g至约4J/g或约3J/g)。形式2多晶型物的第二吸热通常在93℃至约97℃范围内的温度(例如，在约94℃至约96℃范围内的温度或者约95℃的温度)下开始。形式2多晶型物的第二吸热通常在99℃至约103℃范围内的温度(例如，在约100℃至约102℃范围内的温度或者约101℃的温度)下具有峰。通常，形式2多晶型物的第二吸热的焓变为约0.5J/g至约4J/g(例如，约1J/g至约3J/g或约2J/g)。形式2多晶型物的第三吸热通常在180℃至约184℃范围内的温度(例如，在约181℃至约183℃范围内的温度或者约182℃的温度)下开始。形式2多晶型物的第三吸热通常在196℃至约200℃范围内的温度(例如，在约197℃至约199℃范围内的温度或者约198℃的温度)下具有峰。通常，形式2多晶型物的第三吸热的焓变为约25J/g至约29J/g(例如，约26J/g至约28J/g或约27J/g)。
形式2多晶型物可通过以下方法获得，包括：
(a)在存在水和极性质子有机溶剂的情况下，将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸和钠离子源接触以形成溶液；或将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐溶解于包含水和极性质子有机溶剂的溶剂混合物中以形成溶液；以及
(b)从所述溶液获得呈形式2多晶型物的结晶N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐无水物。
在优选实施方案中，在步骤(a)中，将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐溶解于包含水和极性质子有机溶剂的溶剂混合物中以形成溶液。
在优选实施方案中，步骤(a)中所用的极性质子有机溶剂为异丙醇。水与极性质子有机溶剂的体积比通常为1:35至1:1(例如，1:20至1:1、或1:15至1:4、或1:13至1:6、或1:11至1:8或约1:10)。
用于获得形式2多晶型物的另外优选的方法包括极性质子有机溶剂、钠离子源、获得固体钠盐的手段和方法的其他特征均如本文关于本发明的第三方面的方法所述的方法。
本发明的第三方面提供了一种用于制备本发明的第一方面的盐、水合物或溶剂化物或者本发明的第二方面的多晶型形式的方法，所述方法包括：
(a)在存在一种或多种极性溶剂的情况下，将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸和钠离子源接触以形成混合物；以及
(b)从所述混合物获得固体的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐。
在某些实施方案中，步骤(a)中所用的一种或多种极性溶剂为极性溶剂的混合物，例如水和极性有机溶剂的混合物。在此类实施方案中，水与极性有机溶剂的体积比通常为1:35至1:1(例如，1:20至1:1、或1:15至1:4、或1:13至1:6、或1:11至1:8、或约1:10、或约1:9)。
极性溶剂的混合物可为例如水和极性质子有机溶剂的混合物或者水和极性非质子有机溶剂的混合物。合适的极性质子有机溶剂包括：酸，诸如甲酸和乙酸；以及醇，诸如甲醇、乙醇、异丙醇和正丁醇。优选的极性质子有机溶剂为异丙醇。合适的极性非质子有机溶剂包括N-甲基吡咯烷酮、四氢呋喃、2-甲基四氢呋喃、乙酸乙酯、乙酸甲酯、丙酮、二甲基甲酰胺、乙腈、二甲基亚砜和碳酸丙烯酯。优选的极性非质子有机溶剂为丙酮。
在一些实施方案中，极性溶剂的混合物可为水和异丙醇的混合物。在一些实施方案中，极性溶剂的混合物可为水和丙酮的混合物。
钠离子源通常为钠盐。在一些实施方案中，钠盐为固体钠盐。在其他实施方案中，钠盐为含有钠离子的化合物的溶液。合适的固体钠盐包括NaCl、NaOH、Na2CO3和NaHCO3。合适的含有钠离子的化合物的溶液包括甲醇钠(NaOMe)、乙醇钠(NaOEt)和叔丁醇钠(NaOtBu)，其全部在乙醇、四氢呋喃或丙酮或者这些溶剂中的任一种与水的混合物中。其他合适的含有钠离子的化合物的溶液包括在水中的NaCl、NaOH、Na2CO3和NaHCO3。优选的钠离子源为在乙醇中的乙醇钠(NaOEt)或在水中的NaOH。更优选的钠离子源为在乙醇中的乙醇钠(NaOEt)。
在一些实施方案中，在步骤(a)中，形成的反应混合物为溶液。在一些实施方案中，在步骤(a)中，用极性溶剂或极性溶剂的混合物处理N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸，接着添加钠离子源，以形成溶液。
在一些实施方案中，在5℃至100℃范围内、或10℃至60℃范围内、或15℃至30℃范围内的温度下进行步骤(a)。
在一些实施方案中，在步骤(b)中，固体N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐可由反应混合物通过蒸发溶剂或溶剂的混合物来获得。在一些实施方案中，固体N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐可由反应混合物通过添加合适的反溶剂来获得。在此类实施方式中，溶剂或溶剂的混合物与反溶剂的体积比通常为1:1至1:10(例如，1:1.5至1:8、1:2至1:6、或约1:3、或约1:5)。在一些实施方案中，固体N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐可由反应混合物通过添加晶种来获得。在一些实施方案中，固体N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐可由反应混合物通过组合地添加合适的反溶剂并且添加晶种来获得。
合适的反溶剂包括非极性溶剂，诸如己烷、庚烷、环己烷、甲苯、苯、1,4-二噁烷、氯仿、二氯甲烷、乙醚、二异丙醚和叔丁基甲醚。乙醚、二异丙醚和叔丁基甲醚为优选的。特别优选的为叔丁基甲醚.。
在一些实施方案中，在5℃至100℃范围内、或10℃至60℃范围内、或15℃至30℃范围内的温度下进行步骤(b)。
本发明的第四方面提供了一种药物组合物，其包含本发明的第一方面的盐、水合物或溶剂化物或者本发明的第二方面的多晶型形式和药学上可接受的赋形剂。
选择并制备合适的药物制剂的常规程序描述于例如“Aulton's Pharmaceutics-The Design and Manufacture of Medicines”,M.E.Aulton和K.M.G.Taylor,ChurchillLivingstone Elsevier,第4版,2013。
可用于本发明的药物组合物的药学上可接受的赋形剂(包括佐剂、稀释剂或载剂)为常规用于药物制剂的领域的赋形剂且包括但不限于糖、糖醇、淀粉、离子交换剂、氧化铝、硬脂酸铝、卵磷脂、血清蛋白(诸如人血清白蛋白)、缓冲物质(诸如磷酸盐)、甘油、山梨酸、山梨酸钾、饱和植物脂肪酸的部分甘油酯混合物、水、盐或电解质诸如硫酸鱼精蛋白、磷酸氢二钠、磷酸氢钾、氯化钠、锌盐、胶态二氧化硅、三硅酸镁、聚乙烯吡咯烷酮、基于纤维素的物质、聚乙二醇、羧甲基纤维素钠、聚丙烯酸酯、蜡、聚乙烯-聚氧丙烯-嵌段聚合物、聚乙二醇和羊毛脂。
在一个实施方案中，本发明的第四方面的药物组合物另外包含一种或多种另外活性剂。
在另一实施方案中，本发明的第四方面的药物组合物可呈成套药盒的一部分提供，其中所述成套药盒包含本发明的第四方面的药物组合物和一种或多种另外的药物组合物，其中所述一种或多种另外的药物组合物各自包含药学上可接受的赋形剂和一种或多种另外的活性剂。
本发明的第五方面提供了本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或本发明的第四方面的药物组合物，其用于医学和/或用于治疗或预防疾病、病症或病况。通常，所述用途包括向受试者施用所述盐、水合物、溶剂化物、多晶型形式或药物组合物。在一个实施方案中，用途包括共同施用一种或多种另外的活性剂。
如本文所用的术语“治疗”同等地指代治愈性疗法和改善或姑息疗法。所述术语包括获得有益或所需生理学结果，其可为或可不为临床确立的。有益或所需临床结果包括但不限于症状的缓解、症状的预防、疾病程度的减弱、病况的稳定(即不恶化)、病况/症状的进展/恶化的延缓/减慢、病况/症状的改善或缓和和减轻(不管是部分还是总计)，不管是可检测的还是不可检测的。如本文所用的术语“缓和”和其变化意指相比于未施用本发明的盐、水合物、溶剂化物、多晶型形式或药物组合物，生理学病况或症状的程度和/或非所需表现减小和/或进展的时程减慢或延长。如本文关于疾病、病症或病况所用的术语“预防”涉及防治性或预防性疗法，以及减小发展疾病、病症或病况的风险的疗法。术语“预防”包括避免疾病、病症或病况的发生，和延缓疾病、病症或病况的发作。如通过受控的临床试验所测量的任何统计学显著的(p≤0.05)避免发生、延缓发作或减小风险可视为疾病、病症或病况的预防。适于预防的受试者包括如通过遗传或生化标记物所鉴别处于升高的疾病、病症或病况风险的受试者。通常，遗传或生化标记物适合于考虑中的疾病、病症或病况，且可包括例如炎症生物标记物诸如：在炎症的情况下，C反应蛋白(CRP)和单核细胞趋化蛋白1(MCP-1)；在NAFLD和NASH的情况下，总胆固醇、三酸甘油酯、胰岛素抗性和C肽；以及更一般而言，在对NLRP3抑制有应答的疾病、病症或病况的情况下，IL1β和IL18。
本发明的第六方面提供了本发明的第一方面的盐、水合物或溶剂化物或者本发明的第二方面的多晶型形式在制造用于治疗或预防疾病、病症或病况的药剂中的用途。通常，治疗或预防包括向受试者施用所述盐、水合物、溶剂化物、多晶型形式或药剂。在一个实施方案中，所述治疗或预防包括共同施用一种或多种另外的活性剂。
本发明的第七方面提供了一种治疗或预防疾病、病症或病况的方法，所述方法包括以下步骤：施用有效量的本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或第四方面的药物组合物，从而治疗或预防疾病、病症或病况。在一个实施方案中，所述方法还包括共同施用有效量的一种或多种另外的活性剂的步骤。通常，施用是向有需要的受试者进行的。
本发明的第八方面提供了本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或本发明的第四方面的药物组合物，其用于在个体中治疗或预防疾病、病症或病况，其中所述个体具有NLRP3的种系或体细胞非沉默突变。突变可为例如功能获得型突变或其他导致增加的NLRP3活性的突变。通常，用途包括向个体施用所述盐、水合物、溶剂化物、多晶型形式或药物组合物。在一个实施方案中，用途包括共同施用一种或多种另外的活性剂。用途还可包括诊断具有NLRP3的种系或体细胞非沉默突变的个体，其中所述盐、水合物、溶剂化物、多晶型形式或药物组合物是基于突变的阳性诊断来向个体施用的。通常，在个体中NLRP3的突变的鉴别可通过任何合适的遗传或生化手段实现。
本发明的第九方面提供了本发明的第一方面的盐、水合物或溶剂化物或本发明的第二方面的多晶型形式在制造用于在个体中治疗或预防疾病、病症或病况的药剂中的用途，其中所述个体具有NLRP3的种系或体细胞非沉默突变。突变可为例如功能获得型突变或其他导致增加的NLRP3活性的突变。通常，治疗或预防包括向个体施用所述盐、水合物、溶剂化物、多晶型形式或药剂。在一个实施方案中，所述治疗或预防包括共同施用一种或多种另外的活性剂。治疗或预防还可包括诊断具有NLRP3的种系或体细胞非沉默突变的个体，其中所述盐、水合物、溶剂化物、多晶型形式或药剂是基于突变的阳性诊断来向个体施用的。通常，在个体中NLRP3的突变的鉴别可通过任何合适的遗传或生化手段实现。
本发明的第十方面提供了一种治疗或预防疾病、病症或病况的方法，所述方法包括以下步骤：诊断具有NLRP3的种系或体细胞非沉默突变的个体；以及向阳性诊断的个体施用有效量的本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或本发明的第四方面的药物组合物，从而治疗或预防疾病、病症或病况。在一个实施方案中，所述方法还包括共同施用有效量的一种或多种另外的活性剂的步骤。通常，施用是向有需要的受试者进行的。
在一般实施方案中，疾病、病症或病况可为免疫系统、心血管系统、内分泌系统、胃肠道、肾脏系统、肝脏系统、代谢系统、呼吸系统、中枢神经系统的疾病、病症或病况，可为癌症或其他恶性肿瘤，并且/或者可由病原体引起或与病原体相关。
应理解，根据广义的疾病、病症和病况类别所定义的这些一般实施方案并不互相排斥。就此而言，任何具体疾病、病症或病况可根据多于一种上文一般实施方案进行分类。非限制性实例为I型糖尿病，其为自身免疫疾病和内分泌系统的疾病。
在本发明的第五、第六、第七、第八、第九或第十方面的一个实施方案中，疾病、病症或病况对NLRP3抑制有应答。如本文所用，术语“NLRP3抑制”是指NLRP3活性水平的完全或部分减小且包括例如活性NLRP3的抑制和/或NLRP3活化的抑制。
有证据表明NLRP3诱导的IL-1和IL-18在结合大量不同病症或因其而发生的炎症应答中起作用(Menu等人,Clinical and Experimental Immunology,166:1-15,2011；Strowig等人,Nature,481:278-286,2012)。
NLRP3牵涉许多自身炎症性疾病，包括家族性地中海热(FMF)、TNF受体相关的周期性综合征(TRAPS)、高免疫球蛋白D伴周期性发热综合征(HIDS)、化脓性关节炎、坏疽性脓皮症和痤疮(PAPA)、斯威特氏综合征、慢性非细菌骨髓炎(CNO)和寻常性痤疮(Cook等人,Eur.J.Immunol.,40:595-653,2010)。特别是，已发现NLRP3突变引起一组罕见的自身炎症性疾病，称为CAPS(Ozaki等人,J.Inflammation Research,8:15-27,2015；Schroder等人,Cell,140:821-832,2010；和Menu等人,Clinical and Experimental Immunology,166:1-15,2011)。CAPS为特征在于复发性发热和炎症的可遗传疾病，且包括三种自身炎症性病症，其形成临床连续体。按递增严重程度的次序，这些疾病为家族性冷因性自身炎症性综合征(FCAS)、穆克尔-韦尔斯综合征(MWS)和慢性幼儿神经皮肤关节综合征(CINCA；还称为新生儿发病多系统炎症性疾病，NOMID)，且已显示所有均由NLRP3基因的功能获得型突变引起，其引起增加的IL-1β分泌。
已发现许多自身免疫疾病涉及NLRP3，特别是包括多发性硬化、1型糖尿病(T1D)、牛皮癣、类风湿性关节炎(RA)、白塞病、施尼茨勒综合征、巨噬细胞活化综合征(MastersClin.Immunol.2013；Braddock等人,Nat.Rev.Drug Disc.2004 3:1-10；Inoue等人,Immunology 139:11-18；Coll等人,Nat.Med.2015 21(3):248-55；以及Scott等人,Clin.Exp.Rheumatol 2016 34(1):88-93)、全身性红斑性狼疮(Lu等人,J Immunol.2017198(3):1119-29)和全身性硬化(Artlett等人,Arthritis Rheum.2011；63(11):3563-74)。还显示NLRP3在许多肺部疾病包括慢性阻塞性肺病(COPD)、哮喘(包括类固醇抗性哮喘)、石绵沉着病和硅末沉着病(De Nardo等人,Am.J.Pathol.,184:42-54,2014和Kim等人,Am JRespir Crit Care Med.2017 196(3):283-97)。还表明，NLRP3在许多中枢神经系统病况中起作用，包括帕金森氏病(PD)、阿尔茨海默氏病(AD)、失智症、亨丁顿氏病、脑型疟、由肺炎球菌性脑膜炎所致的脑损伤(Walsh等人,Nature Reviews,15:84-97,2014以及Dempsey等人,Brain.Behav.Immun.2017 61:306-316)、颅内动脉瘤(Zhang等人,J.Stroke&Cerebrovascular Dis.2015 24；5:972–979)和创伤性脑损伤(Ismael等人,JNeurotrauma.2018年1月2日)。还显示，NRLP3活性涉及各种代谢疾病，包括2型糖尿病(T2D)、动脉粥样硬化、肥胖、痛风、假性痛风、代谢综合征(Wen等人,Nature Immunology,13:352-357,2012；Duewell等人,Nature,464:1357-1361,2010；Strowig等人,Nature,481:278-286,2012)和非酒精性脂肪性肝炎(Mridha等人,J Hepatol.201766(5):1037-46)。还表明，NLRP3经由IL-1β的作用在以下中：动脉粥样硬化、心肌梗塞(van Hout等人,Eur.Heart J.2017 38(11):828-36)、心脏衰竭(Sano等人,J AM.Coll.Cardiol.201871(8):875-66)、主动脉瘤和夹层(Wu等人,Arterioscler.Thromb.Vasc.Biol.2017 37(4):694-706)和其他心血管事件(Ridker等人,N Engl J Med.,doi:10.1056/NEJMoa1707914,2017)。已显示涉及NLRP3的其他疾病包括：眼部疾病，诸如湿性和干性年龄相关黄斑变性(Doyle等人,Nature Medicine,18:791-798,2012以及Tarallo等人,Cell 2012 149(4):847-59)、糖尿病性视网膜病(Loukovaara等人,Acta Ophthalmol.2017；95(8):803-808)和视神经损伤(Puyang et al.Sci Rep.2016年2月19日；6:20998)；肝部疾病，包括非酒精性脂肪性肝炎(NASH)(Henao-Meija等人,Nature,482:179-185,2012)；肺部和皮肤的炎症性应答(Primiano等人,J Immunol.2016 197(6):2421-33)，包括接触性过敏(诸如大疱性类天疱疮(Fang等人,J Dermatol Sci.2016；83(2):116-23))、特应性皮肤炎(Niebuhr等人,Allergy 2014 69(8):1058-67)、化脓性汗腺炎(Alikhan等人,2009J Am Acad Dermatol60(4):539-61)、寻常性痤疮(Qin等人,J Invest.Dermatol.2014 134(2):381-88)和类肉瘤病(Jager等人,Am J Respir Crit Care Med 2015 191:A5816)；关节的炎症性应答(Braddock等人,Nat.Rev.Drug Disc.,3:1-10,2004)；肌萎缩侧索硬化(Gugliandolo等人,Inflammation 2018 41(1):93-103)；囊肿纤维化(Iannitti等人,Nat.Commun.2016 7:10791)；中风(Walsh等人,Nature Reviews,15:84-97,2014)；慢性肾病(Granata等人,PLoSOne 2015 10(3):e0122272)；以及炎症性肠病，包括溃疡性结肠炎和克罗恩氏病(Braddock等人,Nat.Rev.Drug Disc.,3:1-10,2004；Neudecker等人,J Exp.Med.2017 214(6):1737-52；以及Lazaridis等人,Dig.Dis.Sci.2017 62(9):2348-56)。已发现NLRP3炎症体应答于氧化压力和UVB照射而活化(Schroder等人,Science,327:296-300,2010)。还显示，NLRP3涉及炎症性痛觉过敏(Dolunay等人,Inflammation,40:366-386,2017)。
还提出炎症体和尤其是NLRP3为由各种病原体包括病毒诸如DNA病毒调节的靶标(Amsler等人,Future Virol.(2013)8(4),357-370)。
NLRP3还牵涉许多癌症的发病机理(Menu等人,Clinical and ExperimentalImmunology166:1-15,2011；以及Masters Clin.Immunol.2013)。例如，若干先前研究提出，已显示IL-1β在癌症侵袭性、生长和转移和以卡那单抗的IL-1β的抑制中的作用在随机、双盲、安慰剂对照的试验中减小肺癌的发生率和总癌症死亡率(Ridker等人,Lancet,S0140-6736(17)32247-X,2017)。还显示抑制NLRP3炎症体或IL-1β抑制体外肺癌细胞的增殖和迁移(Wang等人，Oncol Rep.2016；35(4):2053-64)。还表明了NLRP3炎症体在以下方面中的作用：骨髓增生不良综合征(Basiorka等人,Blood.2016年12月22日；128(25):2960-2975)；以及另外各种其他癌症的致癌作用，包括神经胶瘤(Li等人,Am J Cancer Res.2015；5(1):442-449)、炎症诱导的肿瘤(Allen等人,J Exp Med.2010；207(5):1045-56以及Hu等人,PNAS.2010；107(50):21635-40)、多发性骨髓瘤(Li等人,Hematology 2016 21(3):144-51)和头颈部鳞状细胞(Huang等人,J Exp Clin Cancer Res.2017 2；36(1):116)。还显示了NLRP3炎症体的活化介导肿瘤细胞对5-氟尿嘧啶的化学抗性(Feng等人,J Exp ClinCancer Res.2017 21；36(1):81)，并且周围神经中NLRP3炎症体的活化导致化学疗法诱导的神经性疼痛(Jia等人,Mol Pain.2017；13:1-11)。
还显示NLRP3为有效控制病毒、细菌、真菌和蠕虫病原体感染所需的(Strowig等人,Nature,481:278-286,2012)。
因此，可对NLRP3抑制有应答且可根据本发明的第五、第六、第七、第八、第九或第十方面治疗或预防的疾病、病症或病况的实例包括：
(i)炎症，包括因炎症性病症例如自身炎症性疾病所致的炎症、因非炎症性病症的症状所致的炎症、因感染所致的炎症或继发于创伤、损伤或自身免疫的炎症；
(ii)自身免疫性疾病，诸如急性播散性脑脊髓炎、爱迪生氏病、僵直性脊椎炎、抗磷脂质抗体综合征、(APS)、抗合成酶综合征、再生不良性贫血、自身免疫性肾上腺炎、自身免疫性肝炎、自身免疫性卵巢炎、自身免疫性多腺体衰竭、自身免疫性甲状腺炎、乳糜泻、克罗恩氏病、1型糖尿病(T1D)、古巴士德氏综合征、格雷氏病、吉巴氏综合征(GBS)、桥本氏病、特发性血小板减少性紫癫、川崎氏病、红斑狼疮(包括全身性红斑性狼疮(SLE))、多发性硬化(MS)(包括原发性进行性多发性硬化(PPMS)、继发性进行性多发性硬化(SPMS)和复发缓解性多发性硬化(RRMS))、重症肌无力、眼阵挛肌阵挛综合征(OMS)、视神经炎、奥德氏甲状腺炎、天疱疮、恶性贫血、多发性关节炎、原发性胆汁性肝硬化、类风湿性关节炎(RA)、牛皮癣性关节炎、幼年型特发性关节炎或史迪尔氏病、不反应痛风性关节炎、莱特氏综合征、休格连氏综合征、全身性硬化全身性结缔组织症、高安氏动脉炎、颞动脉炎、温抗体型自身免疫性溶血性贫血、韦格纳氏肉芽肿、圆秃、贝赛特氏病、查加斯病、自主神经障碍、子宫内膜异位、化脓性汗腺炎(HS)、间质性膀胱炎、神经性肌强直、牛皮癣、类肉瘤病、硬皮症、溃疡性结肠炎、施尼茨勒综合征、巨噬细胞活化综合征、布劳综合征、白斑病或外阴疼痛；
(iii)癌症，包括肺癌、胰腺癌、胃癌、骨髓增生不良综合征、白血病(包括急性淋巴细胞淋巴细胞性白血病(ALL)和急性骨髓性白血病(AML))、肾上腺癌、肛门癌、基底和鳞状细胞皮肤癌、胆管癌、膀胱癌、骨癌、脑和脊髓瘤、乳癌、子宫颈癌、慢性淋巴细胞淋巴细胞性白血病(CLL)、慢性骨髓性白血病(CML)、慢性骨髓单核细胞性白血病(CMML)、结肠直肠癌、子宫内膜癌、食管癌、伊文肿瘤家族、眼癌、胆囊癌、胃肠类癌瘤、胃肠基质瘤(GIST)、妊娠滋养细胞疾病、神经胶瘤、霍奇金氏淋巴瘤、卡波西氏肉瘤、肾癌、喉和下咽癌、肝癌、肺类癌瘤、淋巴瘤(包括皮肤T细胞淋巴瘤)、恶性间皮瘤、黑色素瘤皮肤癌、默克细胞皮肤癌、多发性骨髓瘤、鼻腔和鼻窦癌、鼻咽癌、神经胚细胞瘤、非霍奇金氏淋巴瘤、非小细胞肺癌、口腔和口咽癌、骨肉瘤、卵巢癌、阴茎癌、垂体肿瘤、前列腺癌、视网膜胚细胞瘤、横纹肌肉瘤、唾腺癌、皮肤癌、小细胞肺癌、小肠癌、软组织肉瘤、胃癌、睾丸癌、胸腺癌、甲状腺癌(包括未分化甲状腺癌)、子宫肉瘤、阴道癌、阴门癌、华氏巨球蛋白血症和威尔姆氏肿瘤；
(iv)感染，包括病毒感染(例如来自流感病毒、免疫缺乏病毒(HIV)、α病毒(诸如屈公病病毒和罗氏河病毒)、黄病毒(诸如登革热病毒和兹卡病毒)、疱疹病毒(诸如爱氏顿病毒、巨细胞病毒、水痘-带状疱疹病毒和KSHV)、痘病毒(诸如痘疮病毒(改质痘苗病毒安卡拉(Ankara))和粘液病毒)、腺病毒(诸如腺病毒5)或乳突病毒)；细菌感染(例如来自金黄色葡萄球菌(Staphylococcus aureus)、幽门螺旋杆菌(Helicobacter pylori)、炭疽杆菌(Bacillus anthracis)、百日咳杆菌(Bordatella pertussis)、类鼻疽伯克氏菌(Burkholderiapseudomallei)、白喉杆菌(Corynebacterium diptheriae)、破伤风杆菌(Clostridium tetani)、肉毒杆菌(Clostridium botulinum)、肺炎链球菌(Streptococcuspneumoniae)、酿脓链球菌(Streptococcus pyogenes)、李斯特菌(Listeriamonocytogenes)、嗜血杆菌(Hemophilus influenzae)、巴氏杆菌(Pasteurellamulticida)、痢疾志贺氏杆菌(Shigella dysenteriae)、结核分枝杆菌(Mycobacteriumtuberculosis)、麻疯分枝杆菌(Mycobacterium leprae)、肺炎霉浆菌(Mycoplasmapneumoniae)、人霉浆菌(Mycoplasma hominis)、脑膜炎双球菌(Neisseriameningitidis)、奈瑟氏淋病双球菌(Neisseria gonorrhoeae)、立克次氏立克次体(Rickettsia rickettsii)、嗜肺性退伍军人杆菌(Legionella pneumophila)、克雷伯氏肺炎杆菌(Klebsiella pneumoniae)、铜绿假单胞菌(Pseudomonas aeruginosa)、痤疮丙酸杆菌(Propionibacterium acnes)、梅毒螺旋体(Treponema pallidum)、披衣菌(Chlamydiatrachomatis)、霍乱弧菌(Vibrio cholerae)、鼠伤寒沙氏杆菌(Salmonella typhimurium,Salmonella typhi)、伯氏疏螺旋体(Borrelia burgdorferi)或鼠疫杆菌(Yersiniapestis))；真菌感染(例如来自念珠菌种或曲菌种)；原虫感染(例如来自疟原虫、焦虫、梨形鞭毛虫、内阿米巴、利什曼原虫或锥虫)；蠕虫感染(例如来自住血吸虫、蛔虫、绦虫或吸虫)；和普里昂蛋白感染；
(v)中枢神经系统疾病，诸如帕金森氏病、阿尔茨海默氏病、失智症、运动神经元疾病、亨丁顿氏病、脑型疟、由肺炎球菌性脑膜炎所致的脑损伤、颅内动脉瘤、创伤性脑损伤和肌萎缩侧索硬化；
(vi)代谢疾病，诸如2型糖尿病(T2D)、动脉粥样硬化、肥胖、痛风和假性痛风；
(vii)心血管疾病，诸如高血压、局部缺血、再灌注损伤(包括MI后缺血性再灌注损伤)、中风(包括缺血性中风)、短暂性缺血性发作、心肌梗塞(包括复发性心肌梗塞)、心脏衰竭(包括充血性心脏衰竭和射血分数维持的心脏衰竭)、栓塞、动脉瘤(包括腹部主动脉瘤)和心包炎(包括卓斯勒氏综合征)；
(viii)呼吸疾病，包括慢性阻塞性肺病(COPD)、哮喘(诸如过敏性哮喘和类固醇抗性哮喘)、石绵沉着病、硅末沉着病、纳米粒子诱导的炎症、囊肿纤维化和特发性肺纤维化；
(ix)肝部疾病，包括非酒精性脂肪肝病(NAFLD)和非酒精性脂肪性肝炎(NASH)包括后期的纤维化F3和F4阶段、酒精性脂肪肝病(AFLD)和酒精性脂肪性肝炎(ASH)；
(x)肾部疾病，包括慢性肾病、草酸性肾病变、肾钙沉积病、肾小球性肾炎和糖尿病肾病变；
(xi)眼部疾病，包括眼部上皮的疾病、年龄相关黄斑变性(AMD)(干性和湿性)、眼色素层炎、角膜感染、糖尿病性视网膜病、视神经损伤、干眼症和青光眼；
(xii)皮肤疾病，包括皮肤炎(诸如接触性皮肤炎和特应性皮肤炎)、接触性过敏、晒伤、皮肤病变、化脓性汗腺炎(HS)、其他囊肿引起的皮肤疾病和聚合性痤疮；
(xiii)淋巴病况，诸如淋巴管炎和卡斯尔曼病(Castleman's disease)；
(xiv)心理病症，诸如忧郁和心理压力；
(xv)移植物抗宿主病；
(xvi)异感痛(allodynia)，包括机械性异感痛(mechanical allodynia)；和
(xvii)已确定个体携带NLRP3的种系或体细胞非沉默突变的任何疾病。
在一个实施方案中，疾病、病症或病况选自：
(i)癌症；
(ii)感染；
(iii)中枢神经系统疾病；
(iv)心血管疾病；
(v)肝部疾病；
(vi)眼部疾病；或
(vii)皮肤疾病。
更通常，疾病、病症或病况选自：
(i)癌症；
(ii)感染；
(iii)中枢神经系统疾病；或
(iv)心血管疾病。
在一个实施方案中，疾病、病症或病况选自：
(i)聚合性痤疮；
(ii)特应性皮肤炎；
(iii)阿尔茨海默氏病；
(iv)肌萎缩侧索硬化；
(v)年龄相关黄斑变性(AMD)；
(vi)未分化甲状腺癌；
(vii)冷吡啉相关周期性综合征(CAPS)；
(viii)接触性皮肤炎；
(ix)囊肿纤维化；
(x)充血性心脏衰竭；
(xi)慢性肾病；
(xii)克罗恩氏病；
(xiii)家族性冷因性自身炎症性综合征(FCAS)；
(xiv)亨丁顿氏病；
(xv)心脏衰竭；
(xvi)射血分数维持的心脏衰竭；
(xvii)缺血性再灌注损伤；
(xviii)幼年型特发性关节炎；
(xix)心肌梗塞；
(xx)巨噬细胞活化综合征；
(xxi)骨髓增生不良综合征；
(xxii)多发性骨髓瘤；
(xxiii)运动神经元疾病；
(xxiv)多发性硬化；
(xxv)穆克尔-韦尔斯综合征；
(xxvi)非酒精性脂肪性肝炎(NASH)；
(xxvii)新生儿发病多系统炎症性疾病(NOMID)；
(xxviii)帕金森氏病；
(xxix)全身型幼年特发性关节炎；
(xxx)全身性红斑性狼疮；
(xxxi)创伤性脑损伤；
(xxxii)短暂性缺血性发作；和
(xxxiii)溃疡性结肠炎。
在本发明的另一典型实施方案中，疾病、病症或病况为炎症。可根据本发明的第五、第六、第七、第八、第九或第十方面治疗或预防的炎症的实例包括结合以下或因其而发生的炎症应答：
(i)皮肤病况，诸如接触性过敏、大疱性类天疱疮、晒伤、牛皮癣、特应性皮肤炎、接触性皮肤炎、过敏性接触性皮肤炎、脂溢性皮肤炎、扁平苔藓、硬皮症、天疱疮、水疱性表皮松解症、风疹块、红斑或脱发；
(ii)关节病况，诸如骨关节炎、全身性幼年型特发性关节炎、成人史迪尔氏病、复发性多发性软骨炎、类风湿性关节炎、幼年型慢性关节炎、痛风或血清阴性脊椎关节病变(例如僵直性脊椎炎、牛皮癣性关节炎或莱特氏病(Reiter's disease))；
(iii)肌肉病况，诸如多发性肌炎或重症肌无力；
(iv)胃肠道病况，诸如炎症性肠病(包括克罗恩氏病和溃疡性结肠炎)、胃溃疡、乳糜泻、直肠炎、胰腺炎、嗜酸性球性胃肠炎(eosinopilic gastro-enteritis)、肥大细胞增多症(mastocytosis)、抗磷脂质综合征或可具有远离肠的作用的与食物有关的过敏症(例如，偏头痛、鼻炎或湿疹)；
(v)呼吸系统病况，诸如慢性阻塞性肺脏疾病(COPD)、哮喘(包括支气管、过敏性、内因性、外因性或粉尘性哮喘，和特别是慢性或痼疾性哮喘，诸如晚期哮喘和气道过度反应)、支气管炎、鼻炎(包括急性鼻炎、过敏性鼻炎、萎缩性鼻炎、慢性鼻炎、干酪性鼻炎、肥厚性鼻炎、化脓性鼻炎(rhinitis pumlenta)、干燥性鼻炎、药物性鼻炎、膜性鼻炎、季节性鼻炎例如花粉热和血管运动型鼻炎)、窦炎、特发性肺纤维化(IPF)、类肉瘤病、农夫肺、硅末沉着病、石绵沉着病、成人呼吸窘迫综合征、过敏性肺炎或特发性间质性肺炎；
(vi)血管病况，诸如动脉粥样硬化、白塞病、血管炎或华格纳氏肉芽病；
(vii)自身免疫性病况，诸如全身性红斑性狼疮、休格连氏综合征、全身性硬化、桥本氏甲状腺炎、I型糖尿病、特发性血小板减少性紫癫或格雷氏病；
(viii)眼部病况，诸如眼色素层炎、过敏性结膜炎或春季结膜炎；
(ix)神经病况，诸如多发性硬化或脑脊髓炎；
(x)感染或与感染有关的病况，诸如后天免疫性缺乏综合征(AIDS)、急性或慢性细菌感染、急性或慢性寄生虫感染、急性或慢性病毒感染、急性或慢性真菌感染、脑膜炎、肝炎(A、B或C型肝炎，或其他病毒性肝炎)、腹膜炎、肺炎、会厌炎、疟疾、登革出血热、利什曼病、链球菌性肌炎、结核杆菌、禽结核杆菌(mycobacterium avium intracellulare)、肺囊虫肺炎(pneumocystis carinii pneumonia)、睾丸炎/副睪丸炎、退伍军人杆菌(legionella)、莱姆病(Lyme disease)、A型流感、埃-巴二氏病毒(epstein-barr virus)、病毒性脑炎/无菌性脑膜炎或骨盆炎症性疾病；
(xi)肾病况，诸如系膜增生性肾小球性肾炎、肾病综合征、肾炎、肾小球肾炎、急性肾衰竭、尿毒症或肾综合征；
(xii)淋巴病况，诸如卡斯尔曼病；
(xiii)免疫系统或涉及免疫系统的病况，诸如高IgE综合征、瘤型麻风(lepromatous leprosy)、家族性噬血性淋巴组织球增生症(familial hemophagocyticlymphohistiocytosis)或移植物抗宿主病；
(xiv)肝病况，诸如慢性主动性肝炎、非酒精性脂肪性肝炎(NASH)、酒精诱导的肝炎、非酒精性脂肪肝病(NAFLD)、酒精性脂肪肝病(AFLD)、酒精性脂肪性肝炎(ASH)或原发性胆汁性肝硬化；
(xv)癌症，包括上文所列举的癌症；
(xvi)烧伤、伤口、创伤、出血或中风；
(xvii)辐射暴露；和/或
(xviii)肥胖；和/或
(xix)疼痛，诸如炎症性痛觉过敏。
在本发明的第五、第六、第七、第八、第九或第十方面的一个实施方案中，疾病、病症或病况为自身炎症性疾病诸如冷吡啉相关周期性综合征(CAPS)、穆克尔-韦尔斯综合征(MWS)、家族性冷因性自身炎症性综合征(FCAS)、家族性地中海热(FMF)、新生儿发病多系统炎症性疾病(NOMID)、肿瘤坏死因子(TNF)受体相关周期性综合征(TRAPS)、高免疫球蛋白D伴周期性发热综合征(HIDS)、白细胞介素1受体拮抗剂缺乏(DIRA)、Majeed综合征、化脓性关节炎、坏疽性脓皮病和痤疮综合征(PAPA)、成人斯蒂尔病(AOSD)、A20单倍剂量不足(HA20)、儿科肉芽肿关节炎(PGA)、PLCG2相关联的抗体缺乏和免疫调节异常(PLAID)、PLCG2相关联的自身炎症性、抗体缺乏和免疫调节异常(APLAID)或含铁母细胞性贫血伴B细胞免疫性缺乏、周期性发热和发展迟缓(SIFD)。
上文列举可对NLRP3抑制有应答且可根据本发明的第五、第六、第七、第八、第九或第十方面治疗或预防的疾病、病症或病况的实例。这些疾病、病症或病况中的一些基本上或全部由NLRP3炎症体活性以及NLRP3诱导的IL-1β和/或IL-18介导。因此，此类疾病、病症或病况可特别对NLRP3抑制有应答，且可特别合适于根据本发明的第五、第六、第七、第八、第九或第十方面的治疗或预防。此类疾病、病症、或病况的实例包括冷吡啉相关周期性综合征(CAPS)、穆克尔-韦尔斯综合征(MWS)、家族性寒冷性自身炎症性综合征(FCAS)、新生儿多系统炎症性疾病(NOMID)、家族性地中海热(FMF)、化脓性关节炎、坏疽性脓皮病和痤疮综合征(PAPA)、高免疫球蛋白D伴周期性发热综合征(HIDS)、肿瘤坏死因子(TNF)受体相关周期性综合征(TRAPS)、全身型幼年特发性关节炎、成人斯蒂尔病(AOSD)、复发性多发性软骨炎、施尼茨勒综合征、斯威特氏综合征、白塞病、抗合成酶综合征、白细胞介素1受体拮抗剂缺乏(DIRA)和A20单倍剂量不足(HA20)。
此外，一些上文提及的疾病、病症或病况由于NLRP3的突变而升高，特别是，导致增加的NLRP3活性。因此，此类疾病、病症或病况可特别对NLRP3抑制有应答，且可特别合适于根据本发明的第五、第六、第七、第八、第九或第十方面的治疗或预防。此类疾病、病症或病况的实例包括冷吡啉相关周期性综合征(CAPS)、穆克尔-韦尔斯综合征(MWS)、家族性冷因性自身炎症性综合征(FCAS)和新生儿发病多系统炎症性疾病(NOMID)。
本发明的第十一方面提供了一种抑制NLRP3的方法，所述方法包括使用本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或本发明的第四方面的药物组合物，以抑制NLRP3。
在本发明的第十一方面的一个实施方案中，所述方法包括使用本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或本发明的第四方面的药物组合物与一种或多种另外活性剂的组合。
在本发明的第十一方面的一个实施方案中，所述方法为离体或体外进行，例如以分析对NLRP3抑制的细胞的作用。
在本发明的第十一方面的另一实施方案中，所述方法是体内进行的。例如，所述方法可包括以下步骤：施用有效量的本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或本发明的第四方面的药物组合物，从而以抑制NLRP3。在一个实施方案中，所述方法还包括共同施用有效量的一种或多种另外的活性剂的步骤。通常，施用是向有需要的受试者进行的。
替代地，本发明的第十一方面的方法可为在非人动物受试者中抑制NLRP3的方法，所述方法包括以下步骤：向非人动物受试者施用所述盐、水合物、溶剂化物、多晶型形式或药物组合物，且任选地随后切断或杀死非人动物受试者。通常，此一方法还包括以下步骤：分析任选地切断或杀死的非人动物受试者的一个或多个组织或流体样本。在一个实施方案中，所述方法还包括共同施用有效量的一种或多种另外的活性剂的步骤。
本发明的第十二方面提供了本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或本发明的第四方面的药物组合物，其用于抑制NLRP3。通常，所述用途包括向受试者施用所述盐、水合物、溶剂化物、多晶型形式或药物组合物。在一个实施方案中，所述盐、水合物、溶剂化物、多晶型形式或药物组合物与一种或多种另外的活性剂共同施用。
本发明的第十三方面提供了本发明的第一方面的盐、水合物或溶剂化物或者本发明的第二方面的多晶型形式在制造用于抑制NLRP3的药剂中的用途。通常，抑制包括向受试者施用所述盐、水合物、溶剂化物、多晶型形式或药剂。在一个实施方案中，所述盐、水合物、溶剂化物、多晶型形式或药剂与一种或多种另外的活性剂共同施用。
在包括使用或共同施用一种或多种另外的活性剂的本发明的第五至第十三方面中任一项的任一实施方案中，所述一种或多种另外的活性剂可包括例如一、二或三种不同另外的活性剂。
所述一种或多种另外的活性剂可彼此和/或在本发明的第一方面的盐、水合物或溶剂化物、本发明的第二方面的多晶型形式或本发明的第四方面的药物组合物之前、与之同时、与之依序或在其之后使用或施用。当所述一种多多种另外的活性剂与本发明的盐、水合物、溶剂化物、多晶型形式或药物组合物同时施用时，可施用本发明的第四方面的药物组合物，其中所述药物组合物另外包含所述一种或多种另外的活性剂。
在包括使用或共同施用一种或多种另外的活性剂的本发明的第五至第十三方面中任一项的一个实施方案中，所述一种或多种另外的活性剂选自：
(i)化学治疗剂；
(ii)抗体；
(iii)烷基化剂；
(iv)抗代谢物；
(v)抗血管生成剂；
(vi)植物碱和/或类萜；
(vii)拓扑异构酶抑制剂；
(viii)mTOR抑制剂；
(ix)二苯乙烯类化合物；
(x)STING激动剂；
(xi)癌症疫苗；
(xii)免疫调节剂；
(xiii)抗生素；
(xiv)抗真菌剂；
(xv)抗肠虫剂；和/或
(xvi)其他活性剂。
应理解，根据广义的活性剂类别所定义的这些一般实施方案并不互相排斥。就此而言，任何具体活性剂可根据多于一种上文一般实施方案进行分类。非限制性实例为乌瑞鲁单抗，其为作为治疗癌症的免疫调节剂的抗体。
在一些实施方案中，所述一种或多种化疗剂选自乙酸阿比特龙(abirateroneacetate)、六甲蜜胺(altretamine)、安吖啶(amsacrine)、脱水长春碱(anhydrovinblastine)、阿里他汀(auristatin)、硫唑嘌呤(azathioprine)、阿霉素(adriamycin)、蓓萨罗丁(bexarotene)、比卡鲁胺(bicalutamide)、BMS 184476、博来霉素(bleomycin)、N,N-二甲基-L-缬氨酰基-L-缬氨酰基-N-甲基-L-缬氨酰基-L-脯氨酰基-L-脯氨酸-叔丁基酰胺、顺铂、卡铂、卡铂环磷酰胺、苯丁酸氮芥(chlorambucil)、恶病质素(cachectin)、西马多丁(cemadotin)、环磷酰胺、卡莫司汀(carmustine)、念珠藻素(cryptophycin)、阿糖胞苷(cytarabine)、欧洲紫杉醇(docetaxel)、欧洲紫杉醇、多柔比星、达卡巴仁(DTIC)、放线菌素、唐霉素、地西他滨(decitabine)、多拉司他汀(dolastatin)、依托泊苷(etoposide)、依托泊苷磷酸盐、恩杂鲁胺(enzalutamide)(MDV3100)、5-氟尿嘧啶、氟达拉滨(fludarabine)、氟他胺、吉西他滨(gemcitabine)、羟基脲和羟基脲紫杉烷、伊达比星(idarubicin)、异环磷酰胺(ifosfamide)、伊立替康(irinotecan)、亚叶酸(leucovorin)、氯尼达明(lonidamine)、洛莫司汀(lomustine)(CCNU)、拉洛他赛(larotaxel)(RPR109881)、二氯甲基二乙酸(mechlorethamine)、巯嘌呤(mercaptopurine)、胺甲喋呤、丝裂霉素C、米托蒽醌(mitoxantrone)、美法仑(melphalan)、米伏布尔(mivobulin)、3',4'-二脱氢-4'-脱氧基-8'-脱甲长春碱(norvin-caleukoblastine)、尼鲁他胺(nilutamide)、奥沙利铂(oxaliplatin)、奥那司酮(onapristone)、泼尼莫司汀(prednimustine)、甲基苄肼(procarbazine)、太平洋紫杉醇(paclitaxel)、含有铂的抗癌剂、2,3,4,5,6-五氟-N-(3-氟-4-甲氧基苯基)苯磺酰胺、泼尼莫司汀、甲基苄根霉素、sertenef、链脲佐菌素(streptozocin)、雌氮芥磷酸盐(stramustine phosphate)、视网酸、他索纳明(tasonermin)、紫杉醇(taxol)、拓扑替康(topotecan)、他莫昔芬(tamoxifen)、替尼泊苷(teniposide)、紫杉烷、替加氟(tegafur)/尿嘧啶、长春新碱(vincristine)、长春碱(vinblastine)、长春瑞滨(vinorelbine)、长春地辛(vindesine)、长春地辛硫酸盐和/或长春氟宁(vinflunine)。
替代地或此外，所述一种或多种化疗剂可选自CD59互补片段、纤连蛋白片段、gro-β(CXCL2)、肝素酶、肝素六糖片段、人绒毛膜促性腺激素(hCG)、干扰素α、干扰素β、干扰素γ、干扰素诱导性蛋白(IP-10)、白细胞介素-12、三环(kringle)5(纤溶酶原片段)、金属蛋白酶抑制剂(TIMP)、2-甲氧基雌二醇、胎盘核糖核酸酶抑制剂、纤溶酶原活化剂抑制剂、血小板因子-4(PF4)、泌乳素16kD片段、泌乳素相关蛋白(PRP)、各种类视色素、四氢皮质醇-S、血小板反应蛋白-1(TSP-1)、转化生长因子-β(TGF-β)、血管抑制素(vasculostatin)、血管新生抑制剂(vasostatin)(钙网蛋白片段)和/或细胞因子(包括白细胞介素，诸如白细胞介素-2(IL-2)或IL-10)。
在一些实施方案中，所述一种或多种抗体可包括一种或多种单克隆抗体。在一些实施方案中，所述一种或多种单克隆抗体选自阿昔单抗(abciximab)、阿达木单抗(adalimumab)、阿仑单抗(alemtuzumab)、阿替珠单抗(atlizumab)、巴利昔单抗(basiliximab)、贝利木单抗(belimumab)、贝伐单抗(bevacizumab)、本妥昔单抗(bretuximabvedotin)、卡那单抗(canakinumab)、西妥昔单抗(cetuximab)、赛妥珠单抗(ceertolizumab pegol)、达利珠单抗(daclizumab)、地诺单抗(denosumab)、依库珠单抗(eculizumab)、依法利珠单抗(efalizumab)、吉妥单抗(gemtuzumab)、戈利木单抗(golimumab)、替伊莫单抗(ibritumomab tiuxetan)、英夫利昔单抗(infliximab)、依匹木单抗(ipilimumab)、莫罗单抗(muromonab)-CD3、那他珠单抗(natalizumab)、奥法木单抗(ofatumumab)、奥马佐单抗(omalizumab)、帕利珠单抗(palivizumab)、帕尼单抗(panitumuab)、兰尼单抗(ranibizumab)、利妥昔单抗(rituximab)、托珠单抗(tocilizumab)、托西莫单抗(tositumomab)和/或曲妥珠单抗(trastuzumab)。
在一些实施方案中，所述一种或多种烷基化剂可包括能够在细胞包括例如癌细胞中存在的条件下烷化亲核官能团的剂。在一些实施方案中，所述一种或多种烷基化剂选自顺铂、卡铂、二氯甲基二乙酸、环磷酰胺、苯丁酸氮芥、异环磷酰胺和/或奥沙利铂。在一些实施方案中，烷基化剂可通过与生物学上重要的分子中的氨基、羧基、硫氢基和/或磷酸酯基团形成共价键影响细胞功能来起作用。在一些实施方案中，烷基化剂可通过修饰细胞的DNA来起作用。
在一些实施方案中，所述一种或多种抗代谢物可包括能够影响或防止RNA或DNA合成的剂。在一些实施方案中，所述一种或多种抗代谢物选自硫唑嘌呤和/或巯嘌呤。
在一些实施方案中，所述一种或多种抗血管生成剂选自内皮他丁(endostatin)、血管生成素抑制剂、血管阻断素(angiostatin)、血管抑制蛋白(angioarrestin)、血纤维静止蛋白(angiostatin)(纤溶酶原片段)、基底膜胶原蛋白衍生的抗血管生成因子(肿瘤抑素(tumstatin)、血管能抑素(canstatin)或抑制蛋白(arrestin))、抗血管生成抗凝血酶III和/或软骨衍生的抑制剂(CDI)。
在一些实施方案中，所述一种或多种植物碱和/或类萜可提供微管功能。在一些实施方案中，所述一种或多种植物碱和/或类萜选自长春花属生物碱(vinca alkaloid)、鬼臼毒素(podophyllotoxin)和/或紫杉烷。在一些实施方案中，所述一种或多种长春花属生物碱可衍生自马达加斯加长春花(Madagascar periwinkle)、粉花红心斑长春花(Catharanthus roseus)(以前称为日日春(Vinca rosea))，且可选自长春新碱、长春碱、长春瑞滨和/或长春地辛。在一些实施方案中，所述一种或多种紫杉烷选自紫杉醇、太平洋紫杉醇、欧洲紫杉醇和/或沃塔紫杉醇(ortataxel)。在一些实施方案中，所述一种或多种鬼臼毒素选自依托泊苷和/或替尼泊苷。
在一些实施方案中，所述一种或多种拓扑异构酶抑制剂选自I型拓扑异构酶抑制剂和/或II型拓扑异构酶抑制剂，且可通过干扰DNA超螺旋来干扰DNA的反转录和/或复制。在一些实施方案中，所述一种或多种I型拓扑异构酶抑制剂可包括喜树碱，其可选自依喜替康(exatecan)、伊立替康、勒托替康(lurtotecan)、拓扑替康、BNP 1350、CKD 602、DB 67(AR67)和/或ST 1481。在一些实施方案中，所述一种或多种II类拓扑异构酶抑制剂可包括表鬼臼毒素(epipodophyllotoxin)，其可选自安吖啶、依托泊苷、依托泊苷磷酸盐和/或替尼泊苷。
在一些实施方案中，所述一种或多种mTOR(雷帕霉素(rapamycin)哺乳动物靶，还称为雷帕霉素机理靶)抑制剂选自雷帕霉素、依维莫司(everolimus)、替西罗莫司(temsirolimus)和/或地佛莫司(deforolimus)。
在一些实施方案中，所述一种或多种二苯乙烯类选自白藜芦醇、云杉醇(piceatannol)、赤松素(pinosylvin)、紫檀芪(pterostilbene)、α-葡萄素、蛇葡萄素(ampelopsin)A、蛇葡萄素E、diptoindonesin C、diptoindonesin F、epsilon-葡萄素、flexuosol A、gnetin H、hemsleyanol D、希腊苯酚(hopeaphenol)、反式diptoindonesinB、白皮杉醇葡萄糖苷(astringin)、白藜芦醇苷(piceid)和/或diptoindonesin A。
在一些实施方案中，所述一种或多种STING(干扰素基因刺激蛋白，还称为跨膜蛋白(TMEM)173)激动剂可包括环双核苷酸(cyclic di-nucleotide)，诸如cAMP、cGMP和cGAMP，和/或修饰环双核苷酸，其可包括以下修饰特征的一个或多个：2'-O/3'-O键联、硫代磷酸酯键联、腺嘌呤和/或鸟嘌呤类似物和/或2'-OH修饰(例如，以甲基基团保护2'-OH或由-F或-N3置换2'-OH)。
在一些实施方案中，所述一种或多种癌症疫苗选自HPV疫苗、乙型肝炎疫苗、Oncophage和/或Provenge。
在一些实施方案中，所述一种或多种免疫调节剂可包括免疫核查点抑制剂。免疫核查点抑制剂可靶向免疫核查点受体，或包括例如以下的受体的组合：CTLA-4、PD-1、PD-L1、PD-L2、T细胞免疫球蛋白和粘蛋白3(TIM3或HAVCR2)、半乳糖凝集素(galectin)9、磷脂丝氨酸、淋巴细胞活化基因3蛋白(LAG3)、I类MHC、II类MHC、4-1BB、4-1BBL、OX40、OX40L、GITR、GITRL、CD27、CD70、TNFRSF25、TL1A、CD40、CD40L、HVEM、LIGHT、BTLA、CD160、CD80、CD244、CD48、ICOS、ICOSL、B7-H3、B7-H4、VISTA、TMIGD2、HHLA2、TMIGD2、嗜乳脂蛋白(butyrophilin)(包括BTNL2)、Siglec家族成员、TIGIT、PVR、杀手细胞类免疫球蛋白受体、ILT、白血球类免疫球蛋白受体、NKG2D、NKG2A、MICA、MICB、CD28、CD86、SIRPA、CD47、VEGF、神经纤毛蛋白、CD30、CD39、CD73、CXCR4和/或CXCL12。
在一些实施方案中，免疫核查点抑制剂选自乌瑞鲁单抗、PF-05082566、MEDI6469、TRX518、varlilumab、CP-870893、派姆单抗(pembrolizumab)(PD1)、纳武单抗(nivolumab)(PD1)、阿特立单抗(atezolizumab)(以前为MPDL3280A)(PD-L1)、MEDI4736(PD-L1)、阿维单抗(avelumab)(PD-L1)、PDR001(PD1)、BMS-986016、MGA271、利鲁单抗(lirilumab)、IPH2201、埃玛株单抗(emactuzumab)、INCB024360、盖伦萨替(galunisertib)、ulocuplumab、BKT140、巴维昔单抗(bavituximab)、CC-90002、贝伐珠单抗和/或MNRP1685A。
在一些实施方案中，所述一种或多种抗生素选自阿米卡星(amikacin)、庆大霉素(gentamicin)、卡那霉素(kanamycin)、新霉素(neomycin)、奈替霉素(netilmicin)、妥布霉素(tobramycin)、巴龙霉素(paromomycin)、链霉素、观霉素(spectinomycin)、格尔德霉素(geldanamycin)、除莠霉素(herbimycin)、利福昔明(rifaximin)、罗拉卡倍芙(loracarbef)、厄他培南(ertapenem)、多尼培南(doripenem)、伊米配能(imipenem)、西司他丁(cilastatin)、美罗培南(meropenem)、赐福得修(cefadroxil)、西华乐林(cefazolin)、噻孢霉素(cefalotin)、头孢霉素(cefalothin)、先锋力可新(cefalexin)、头孢克洛(cefaclor)、头孢孟多酯(cefamandole)、头孢西丁(cefoxitin)、头孢丙烯(cefprozil)、头孢呋辛(cefuroxime)、头孢克肟(cefixime)、头孢地尼(cefdinir)、头孢托仑(cefditoren)、头孢哌酮(cefoperazone)、头孢噻肟(cefotaxime)、头孢泊肟(cefpodoxime)、头孢他啶(ceftazidime)、头孢布烯(ceftibuten)、头孢唑肟(ceftizoxime)、头孢曲松(ceftriaxone)、头孢吡肟(cefepime)、头孢洛林(ceftarolinefosamil)、头孢比普(ceftobiprole)、替考拉宁(teicoplanin)、万古霉素(vancomycin)、泰拉万星(telavancin)、达巴万星(dalbavancin)、奥利万星(oritavancin)、克林霉素(clindamycin)、林可霉素(lincomycin)、达托霉素(daptomycin)、阿奇霉素(azithromycin)、克拉霉素(clarithromycin)、地红霉素(dirithromycin)、红霉素(erythromycin)、罗红霉素(roxithromycin)、醋竹桃霉素(troleandomycin)、泰利霉素(telithromycin)、螺旋霉素(spiramycin)、氨曲南(aztreonam)、富来顿(furazolidone)、硝基呋喃妥因(nitrofurantoin)、利奈唑胺(linezolid)、泼斯唑胺(posizolid)、雷得唑胺(radezolid)、泰地唑胺(torezolid)、阿莫西林(amoxicillin)、安比西林(ampicillin)、阿诺西林(azlocillin)、卡比西林(carbenicillin)、氯洒西林(cloxacillin)、达可西林(dicloxacillin)、氟氯西林(flucloxacillin)、美洛西林(mezlocillin)、甲氧西林(methicillin)、萘夫西林(nafcillin)、扼煞西林(oxacillin)、青霉素G、青霉素V、必倍西林(piperacillin)、替莫西林(temocillin)、替卡西林(ticarcillin)、克拉维酸(calvulanate)、安比西林、舒巴坦(subbactam)、他唑巴坦(tazobactam)、替卡西林、克拉维酸、枯草菌素、粘菌素、多黏菌素B、赛普沙星(ciprofloxacin)、依诺沙星(enoxacin)、加替沙星(gatifloxacin)、吉米沙星(gemifloxacin)、左氧氟沙星(levofloxacin)、洛美沙星(lomefloxacin)、莫西沙星(moxifloxacin)、萘啶酮酸(nalidixic acid)、诺氟沙星(norfloxacin)、氧氟沙星(ofloxacin)、曲氟沙星(trovafloxacin)、格帕沙星(grepafloxacin)、司帕沙星(sparfloxacin)、替马沙星(temafloxacin)、每芬耐(mafenide)、乙酰磺胺、磺胺嘧啶、磺胺嘧啶银(silver sulfadiazine)、达美磺胺(sulfadimethoxine)、磺胺甲异噁唑、氨苯磺胺(sulfanamide)、柳氮磺吡啶(sulfasalazine)、磺胺异噁唑(sulfisoxazole)、美坐磺胺曲美普林(trimethoprim-sulfamethoxazole)、磺酰胺柯衣定(sulfonamideochrysoidine)、去甲基氯四环素(demeclocycline)、米诺四环素(minocycline)、羟四环素(oytetracycline)、四环素(tetracycline)、氯法齐明(clofazimine)、达普颂(dapsone)、达普利霉素(dapreomycin)、环丝胺酸、乙胺丁醇、乙硫异烟酰胺、异烟酸酊、吡嗪甲酰胺、利福平(rifampicin)、利福布汀(rifabutin)、利福喷丁(rifapentine)、链霉素、砷凡纳明(arsphenamine)、氯霉素、弗斯霉素(fosfomycin)、梭链孢酸(fusidic acid)、甲硝唑(metronidazole)、莫匹罗星(mupirocin)、平板霉素(platensimycin)、奎奴普丁(quinupristin)、达福普汀(dalopristin)、甲磺氯霉素(thiamphenicol)、替加环素(tigecycyline)、替硝唑(tinidazole)、甲氧苄啶(trimethoprim)和/或泰斯巴汀(teixobactin)。
在一些实施方案中，所述一种或多种抗生素可包括一种或多种细胞毒性抗生素。在一些实施方案中，所述一种或多种细胞毒性抗生素选自放线菌素、蒽醌、蒽环、沙利度胺(thalidomide)、二氯乙酸、烟酸、2-脱氧葡糖酸和/或氯法齐明(chlofazimine)。在一些实施方案中，所述一种或多种放线菌素选自放线菌素D、枯草菌素、粘菌素(多粘菌素E)和/或多粘菌素B。在一些实施方案中，所述一种或多种蒽醌选自米托蒽醌(mitoxantrone)和/或比生群(pixantrone)。在一些实施方案中，所述一种或多种蒽环选自博来霉素、多柔比星(阿霉素)、唐霉素(道诺霉素)、表柔比星(epirubicin)、伊达比星(idarubicin)、丝裂霉素、普卡霉素和/或戊柔比星(valrubicin)。
在一些实施方案中，所述一种或多种抗真菌剂选自联苯苄唑(bifonazole)、布康唑(butoconazole)、克氯霉唑(clotrimazole)、益康唑(econazole)、酮康唑(ketoconazole)、卢立康唑(luliconazole)、咪康唑(miconazole)、奥莫康唑(omoconazole)、奥昔康唑(oxiconazole)、舍他康唑(sertaconazole)、硫可吖唑(sulconazole)、噻康唑(tioconazole)、阿巴康唑(albaconazole)、艾氟康唑(efinaconazole)、依普康唑(epoziconazole)、氟康那唑(fluconazole)、艾沙康唑(isavuconazole)、伊曲康唑(itraconazole)、泊沙康唑(posaconazole)、丙环唑(propiconazole)、雷夫康唑(ravusconazole)、特康唑(terconazole)、伏立康唑(voriconazole)、阿巴芬凈(abafungin)、阿莫罗芬(amorolfin)、布特那芬(butenafine)、萘替芬(naftifine)、特比奈芬(terbinafine)、阿尼芬净(anidulafungin)、卡泊芬净(caspofungin)、米卡芬净(micafungin)、苯甲酸、环吡酮(ciclopirox)、弗路欣(flucytosine)、5-氟胞嘧啶、灰黄霉素(griseofulvin)、卤普罗近(haloprogin)、托奈福特(tolnaflate)、十一烯酸(undecylenic acid)和/或秘鲁香胶。
在一些实施方案中，所述一种或多种抗肠虫剂选自苯并咪唑(包括阿苯达唑(albendazole)、美边达唑(mebendazole)、噻苯达唑(thiabendazole)、芬苯达唑(fenbendazole)、三氯苯达唑(triclabendazole)和氟苯达唑(flubendazole))、阿巴汀(abamectin)、乙胺嗪(diethylcarbamazine)、伊维菌素(ivermectin)、苏拉明(suramin)、双羟萘酸噻嘧啶(pyrantel pamoate)、左旋咪唑(levamisole)、水杨酸酰苯胺(salicylanilide)(包括耐克螺(niclosamide)和羟氯扎胺(oxyclozanide))和/或硝唑尼特(nitazoxanide)。
在一些实施方案中，其他活性剂选自生长抑制剂、消炎剂(包括非类固醇消炎剂)、抗牛皮癣剂(包括葱酚和其衍生物)、维生素和维生素衍生物(包括类视色素和VDR受体配体)、皮质类固醇、离子通道阻断剂(包括钾离子通道阻断剂)、免疫系统调节剂(包括环孢素、FK 506和糖皮质素)、黄体激素释放激素激动剂(诸如柳普林(leuprolidine)、戈舍瑞林(goserelin)、曲普瑞林(triptorelin)、组氨瑞林(histrelin)、比卡鲁胺(bicalutamide)、氟他胺(flutamide)和/或尼鲁米特(nilutamide))和/或激素(包括雌激素)。
除非另外说明，否则在本发明的第五至第十三方面中任一项中，受试者可为任何人或另一动物。通常，受试者为哺乳动物，更通常为人或驯养哺乳动物诸如奶牛、猪、羔羊、绵羊、山羊、马、猫、狗、兔、小鼠等。更通常，受试者为人。
本发明中采用的任何药剂都可以通过口服、肠胃外(包括静脉、皮下、肌肉内、皮内、气管内、腹膜内、关节内、颅内和硬膜外)、气道(气溶胶)、直肠、阴道、眼或局部(包括透皮、颊面、粘膜、舌下和局部眼)施用来施用。
通常，所选择的施用模式为最适合于待治疗或预防的病症、疾病或病况的施用模式。当施用一种或多种另外的活性剂时，施用模式可与本发明的盐、水合物、溶剂化物、多晶型形式或药物组合物的施用模式相同或不同。
对于口服施用，本发明的盐、水合物、溶剂化物、多晶型形式或药物组合物将一般以片剂、胶囊、硬质或软质明胶胶囊、囊片、口含锭或菱形锭的形式，呈粉剂或颗粒剂，或呈水溶液、混悬液或分散液来提供。
用于口服用途的片剂可包括与药学上可接受的赋形剂诸如惰性稀释剂、崩解剂、粘合剂、润滑剂、甜味剂、调味剂、着色剂和防腐剂混合的活性成分。合适的惰性稀释剂包括碳酸钠和碳酸钙、磷酸钠和磷酸钙以及乳糖。玉米淀粉和海藻酸为合适的崩解剂。粘合剂可包括淀粉和明胶。润滑剂(存在时)可为硬脂酸镁、硬脂酸或滑石。需要时，片剂可用一定材料包衣以延缓在胃肠道中的吸收，所述材料诸如单硬脂酸甘油酯或二硬脂酸甘油酯。片剂还可为泡腾和/或溶解性片剂。
用于口服用途的胶囊包括活性成分与固态稀释剂混合的硬质明胶胶囊以及活性成分与水或油诸如花生油、液体石蜡或橄榄油混合的软质明胶胶囊。
用于口服用途的粉剂或颗粒剂可提供于药囊或药桶中。水溶液、混悬液或分散液可通过向粉剂、颗粒剂或片剂添加水来制备。
合适于口服施用的任何形式可任选地包括甜味剂诸如糖、调味剂、着色剂和/或防腐剂。
用于直肠施用的制剂可提供为具有包括例如可可脂或水杨酸酯的合适基质的栓剂。
合适于阴道施用的制剂可提供为阴道栓、卫生棉塞、乳膏、凝胶、糊剂、泡沫或喷雾制剂，其除活性成分外还含有诸如本领域中已知为适当的载剂。
对于肠胃外用途，本发明的盐、水合物、溶剂化物或多晶型形式将一般提供于无菌水溶液或混悬液中，所述无菌水溶液或混悬液被缓冲至适当pH和等渗性。合适的水性媒介物包括林格氏溶液和等渗氯化钠或葡萄糖。根据本发明的水性混悬液可包括悬浮剂诸如纤维素衍生物、海藻酸钠、聚乙烯吡咯烷酮和黄蓍胶，以及润湿剂诸如卵磷脂。用于水性混悬液的合适防腐剂包括对羟基苯甲酸乙酯和对羟基苯甲酸正丙酯。本发明的盐、水合物、溶剂化物、多晶型形式或药物组合物还可提供为脂质体制剂。
对于眼部施用，本发明的盐、水合物、溶剂化物或多晶型形式将一般以合适于局部施用的形式提供，例如作为滴眼液。合适的形式可包括眼用溶液、凝胶形成溶液、复原用无菌粉剂、眼用混悬液、眼用软膏、眼用乳剂、眼用凝胶和眼用插入物。替代地，本发明的盐、水合物、溶剂化物或多晶型形式可以合适于其他类型的眼部施用的形式提供，例如作为眼内制剂(包括作为冲洗液，作为眼内、玻璃体内或巩膜旁注射制剂，或作为玻璃体内植入物)，作为眼膜(pack)或角膜罩(corneal shield)，作为腔内、结膜下或球后注射制剂，或作为离子导入制剂。
对于经皮和其他局部施用，本发明的盐、水合物、溶剂化物、多晶型形式或药物组合物将一般以软膏、泥罨剂(泥敷剂)、糊剂、粉剂、敷料、乳膏、石膏或贴剂的形式提供。
合适的混悬液和溶液可用于吸入器中以用于气道(气溶胶)施用。
本发明的盐、水合物、溶剂化物或多晶型形式的剂量将当然随待治疗或预防的疾病、病症或病况而不同。一般而言，合适的剂量将在每天每千克接受者体重0.01至500mg的范围内。所需剂量可以适当间隔提供，诸如每隔一天一次、一天一次、一天两次、一天三次或一天四次。所需剂量可以单位剂型施用，例如，其含有每单位剂型1mg至50g活性成分。
为避免存疑，只要可实践，本发明的给定方面的任一实施方案可与本发明的相同方面的任一其他实施方案组合发生。此外，只要可实践，应理解，本发明的任一方面的任一优选、典型或任选的实施方案还应视为本发明的任一其他方面的优选、典型或任选的实施方案。
实施例
除非另外说明，否则所有溶剂、试剂和化合物均为购买的且在没有进一步纯化的情况下即使用。
在以下条件下进行实施例中提及的X射线粉末衍射(XRPD)、离子色谱法(IC)、卡尔-费休滴定(KF)、热重分析(TGA)、差示扫描量热法(DSC)和高效液相色谱法(HPLC)技术：
XRPD衍射图是在Bruker D8衍射仪上使用CuKα辐射(40kV，40mA)和配有Ge单色仪的θ-2θ测角计收集的。入射光束穿过2.0mm发散狭缝，然后穿过0.2mm防散射狭缝和刀口。衍射光束通过带有2.5°Soller狭缝的8.0mm接收狭缝，然后通过Lynxeye检测器。用于数据收集和分析的软件分别为Diffrac Plus XRD Commander和Diffrac Plus EVA。使用原样粉末在环境条件下将样品以平板状试样的形式进行。通过轻轻地压在平坦表面上或填充到切割腔中来在抛光的零背景(510)硅晶片上制备样品。使样品在其自身平面上旋转。所用的s数据收集方法的详情如下：
·角度范围：2至42°2θ
·步长大小：0.05°2θ
·收集时间：0.5s/步(总收集时间：6.40min)
使用IC MagicNet软件，在具有858Professional自动取样机和800Dosino剂量单位监控器的Metrohm 930Compact IC Flex上收集IC数据。将精确称量的样品在合适的溶剂中制备为储备溶液。通过与正分析的已知离子浓度的标准溶液进行比较来实现定量。除非另外说明，否则重复进行分析并且给出值的平均值。
阳离子色谱法的IC方法
阴离子离子色谱法的IC方法
使用Hydranal Coulomat AG oven试剂和氮气吹扫，在150℃的Metrohm 874Oven样品处理器和851Titrano库仑计上进行KF分析。将称量的固体样品引入密封的样品瓶中。每次滴定使用约10mg样品，并且进行重复测定。除非另外说明，否则提供这些结果的平均值。使用Tiamo软件进行数据收集和分析。
在配备有25位自动取样器的TA Instruments Discovery TGA上收集TGA数据。通常，将5-10mg的每种样品加载到预称皮重的铝DSC锅中并且在10℃/min下从环境温度加热至350℃。在样品上保持在25ml/min下的氮气吹扫。仪器控制软件为TRIOS，并且使用TRIOS或Universal Analysis分析数据。
在配备有50位自动取样器的TA Instruments Q2000上收集DSC数据。通常，在针孔式铝锅中将0.5-3mg的每种样品在10℃/min下从25摄氏度加热至300℃。在样品上保持在50ml/min下的干燥氮气吹扫。每60秒(周期)使用2℃/min的基本加热速率和±0.636℃(振幅)的温度调制参数进行温度调制式DSC。仪器控制软件为Q系列Advantage和ThermalAdvantage，并使用Universal Analysis或TRIOS分析数据。
在配备有二极管阵列检测器并使用ChemStation软件的Agilent HP1100系列系统上进行反相HPLC纯度分析。
化学纯度测定的HPLC方法
实施例1：N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-
吡唑-3-磺酰胺单钠一水合物(形式1)
将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸称重至四个小瓶中(每小瓶50mg)。将NaOH(在水中1M)(添加的当量/体积参见表3)和水(4ml)添加至每个样品小瓶中。这些样品经历的条件汇总于表3中。使样品在溶液中保持搅拌，持续3小时。然后尝试通过旋转蒸发仪来除去水，但是3小时后除去的水的量很小。然后将溶液散布在载玻片上以在室温下蒸发。通过XRPD、1H-NMR、HPLC、IC和KF收集并分析形成的固体。IC和KF分析确认了单钠盐一水合物的形成。XRPD分析确认了形式1多晶型物的形成。
表3
实施例2：N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-
吡唑-3-磺酰胺单钠一水合物(形式1)
将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸(50mg)用丙酮和水的9:1(v:v)溶剂混合物(0.5ml)处理。在25℃下搅拌所得悬浮液，之后添加NaOEt(1.1当量，1M EtOH溶液)。添加另外的NaOEt溶液，直至完全溶解(总计1.3当量NaOEt)。将叔丁基甲醚反溶剂(0.25ml)添加至每种样品中，之后添加N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠一水合物形式1多晶型物的晶种(约2-4％)。添加另外的叔丁基甲醚反溶剂以得到最终溶剂:反溶剂比率为1:3(实施例2A)和1:5(实施例2B)。然后在25℃下搅拌样品，持续2小时，之后通过PE玻璃料分离出固体。然后在真空、室温下储存样品，持续18小时，之后通过XRPD、1H-NMR、HPLC、IC、KF、TGA和DSC进行分析。
表4
| 实施例 | 最终溶剂:反溶剂比率 | 产率 | HPLC纯度 |
| 2A | 1:3 | 34％ | 98.1％ |
| 2B | 1:5 | 85％ | 97.6％ |
IC和KF分析确认了单钠盐一水合物的形成。XRPD分析确认了形式1多晶型物的形成。XRPD光谱显示于图1中。TGA和DSC光谱显示于图2中。
图1中所示的XRPD光谱是在制备产物之后、在40℃和75％相对湿度下储存1周和5周之后以及在25℃和97％相对湿度下储存1周和5周之后直接获得的。图1中所示的XRPD光谱显示，在升高的温度和湿度下储存之后，在实施例2中所获得的产物显示相对于转化成其他多晶型形式的稳定性。
实施例3：N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-
吡唑-3-磺酰胺单钠无水物(形式2)
将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐(500mg)用异丙醇和H2O的10:1(v:v)溶剂混合物(30ml)处理，并且使反应混合物在25℃下保持搅拌30分钟。然后将所得澄清溶液蒸发以产生结晶固体，通过XRPD、1H-NMR、HPLC、IC、KF、TGA和DSC对其进行分析。
IC和KF分析确认了单钠盐无水物的形成。HPLC纯度为96.5％。XRPD分析确认了形式2多晶型物的形成。XRPD光谱显示于图3中。TGA和DSC光谱显示于图4中。
图3中所示的XRPD光谱是在制备产物之后、在40℃和75％相对湿度下储存1周之后以及在25℃和97％相对湿度下储存1周之后直接获得的。图3还显示了供参考的形式1多晶型物的XRPD光谱。图3中所示的XRPD光谱指示，在实施例3中所获得的单钠无水物(形式2)在升高的温度(40℃)下是稳定的，并且在升高的湿度(97％RH)下转化为单钠一水合物(形式1)。
比较实施例1：N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙
基-1H-吡唑-3-磺酰胺游离酸
如WO 2016/131098A1中所述制备N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸。
比较实施例2：N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙
基-1H-吡唑-3-磺酰胺钾盐
称重N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸(100mg)并且添加KOH(1.1当量，1M水溶液，283μl)。添加水，并将反应混合物在室温下搅拌直至获得澄清溶液。使反应混合物保持搅拌2小时，然后通过旋转蒸发过夜来除去水，以产生固体，通过XRPD、1H-NMR、HPLC和IC对其进行分析。
IC分析确认了钾盐的形成。HPLC纯度为96.3％。XRPD分析显示完全非晶材料，没有明显的衍射峰。
通过从乙腈或异丙醇蒸发将钾盐转化为结晶物质的尝试均未成功，在每种情况下均产生胶状物。
评估实施例1
评估实施例2的钠盐和比较实施例1的游离酸的在水中的溶解度、在水介质中的稳定性和固有溶解速率。结果示出于表5中。
表5
在水中测量热力学水溶性。发现钠盐可溶于水(81mg/ml)，所得pH为9.7。发现游离酸在水中的溶解性非常差(<0.5mg/ml)。
为了测量在水性介质中的稳定性，将钠盐以0.2mg/ml的浓度溶解于水中。由于游离酸的水溶性很差，所以将游离酸以0.2mg/ml的相同浓度溶解于水和乙腈的1:1混合物中。将样品在50℃下保存在琥珀色小瓶中并且在室温下保存于琥珀色小瓶以及透明小瓶中。发现钠盐在水性介质中稳定，然而发现游离酸不稳定。
通过美国药典第1087章中示出的程序测量固有溶解速率。发现钠盐的固有溶解速率高达游离酸的固有溶解速率的至少两倍。
与比较实施例1和2的游离酸和钾盐相比，实施例1、2和3的钠盐具有改进的性质。这些改进的性质包括结晶度、水溶性、固有溶解速率、在升高的温度和/或相对湿度下储存时的稳定性以及在水性介质中的稳定性。
应理解，上文仅凭借实施例描述本发明。实施例决不意欲限制本发明的范围。可以在不脱离本发明的范围和精神的情况下进行各种修改和实施方案，本发明仅由以下权利要求范围加以定义。
Claims (20)
1.一种N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物。
2.根据权利要求1所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物，其中所述N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐为单钠盐。
3.根据权利要求1所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物，其中所述N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐水合物为一水合物。
4.根据权利要求1所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物，其中所述N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐水合物为N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物。
5.根据权利要求4所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物，其中所述N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物为多晶型形式，其XRPD光谱包括在以下处的峰：4.3°2θ、8.7°2θ和20.6°2θ，均±0.2°2θ。
6.根据权利要求4所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物，其中所述N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物为多晶型形式，其XRPD光谱中的10个最强峰包括5个或更多个具有选自以下的2θ值的峰：4.3°2θ、6.2°2θ、6.7°2θ、7.3°2θ、8.7°2θ、9.0°2θ、12.1°2θ、15.8°2θ、16.5°2θ、18.0°2θ、18.1°2θ、20.6°2θ、21.6°2θ和24.5°2θ，均±0.2°2θ。
7.一种用于制备N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐的方法，其包括：
(a)在存在一种或多种极性溶剂的情况下，将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸和钠离子源接触以形成混合物；以及
(b)从所述混合物获得固体的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐。
8.权利要求7所述的方法，其中步骤(a)中所用的所述极性溶剂包括水和极性非质子有机溶剂。
9.权利要求8所述的方法，其中步骤(a)中所用的所述极性非质子有机溶剂为丙酮。
10.权利要求7-9任一项所述的方法，其中所述N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐是在步骤(b)中通过添加反溶剂获得的。
11.权利要求10所述的方法，其中所述反溶剂为叔丁基甲醚。
12.一种用于制备权利要求5或6中所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物的方法，其包括：
(a)在存在水和任选地极性非质子有机溶剂的情况下，将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺游离酸和钠离子源接触以形成溶液；或将N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐溶解于包含水和任选地极性非质子有机溶剂的溶剂混合物中以形成溶液；以及
(b)从所述溶液获得权利要求5或6中所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物。
13.权利要求12所述的方法，其中步骤(a)中所用的所述极性非质子有机溶剂为丙酮。
14.权利要求12或13所述的方法，其中所述N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺单钠盐一水合物是在步骤(b)中通过添加反溶剂获得的。
15.权利要求14所述的方法，其中所述反溶剂为叔丁基甲醚。
16.一种药物组合物，其包含权利要求1至6中任一项所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物和药学上可接受的赋形剂。
17.权利要求1至6中任一项所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物、或者权利要求16所述的药物组合物在制备用于治疗或预防疾病、病症或病况的药物中的用途，所述疾病、病症或病况对NLRP3抑制有应答。
18.权利要求1至6中任一项所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物、或者权利要求16所述的药物组合物在制备用于治疗或预防疾病、病症或病况的药物中的用途，所述疾病、病症或病况选自：
(i)炎症；
(ii)自身免疫性疾病；
(iii)癌症；
(iv)感染；
(v)中枢神经系统疾病；
(vi)代谢疾病；
(vii)心血管疾病；
(viii)呼吸疾病；
(ix)肝部疾病；
(x)肾病；
(xi)眼部疾病；
(xii)皮肤疾病；
(xiii)淋巴病况；
(xiv)心理病症；
(xv)移植物抗宿主病；
(xvi)异感痛；以及
(xvii)已确定个体携带NLRP3的种系或体细胞非沉默突变的任何疾病。
19.权利要求1至6中任一项所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物、或者权利要求16所述的药物组合物在制备用于治疗或预防疾病、病症或病况的药物中的用途，所述疾病、病症或病况选自：
(i)冷吡啉相关周期性综合征；
(ii)穆克尔-韦尔斯综合征；
(iii)家族性冷因性自身炎症性综合征；
(iv)新生儿发病多系统炎症性疾病；
(v)家族性地中海热；
(vi)化脓性关节炎、坏疽性脓皮病和痤疮综合征；
(vii)高免疫球蛋白D伴周期性发热综合征；
(viii)肿瘤坏死因子受体相关性周期发热综合征；
(ix)全身型幼年特发性关节炎；
(x)成人斯蒂尔病；
(xi)复发性多软骨炎；
(xii)施尼茨勒综合征；
(xiii)斯威特氏综合征；
(xiv)白塞病；
(xv)抗合成酶综合征；
(xvi)白细胞介素1受体拮抗剂缺乏；和
(xvii)A20单倍剂量不足。
20.一种离体或体外抑制NLRP3的方法，所述方法包括使用权利要求1至6中任一项所述的N-((1,2,3,5,6,7-六氢-对称引达省-4-基)氨基甲酰基)-1-异丙基-1H-吡唑-3-磺酰胺钠盐或其水合物、或者权利要求13所述的药物组合物，以抑制NLRP3。
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| PCT/EP2019/060311 WO2019206871A1 (en) | 2018-04-23 | 2019-04-23 | A sodium salt of n-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1 -isopropyl-1 h-pyrazole-3-sulfonamide |
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Families Citing this family (24)
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| TW201837021A (zh) | 2017-01-23 | 2018-10-16 | 美商傑庫爾醫療股份有限公司 | 作為介白素-1活性抑制劑之化合物 |
| US11840543B2 (en) | 2017-05-24 | 2023-12-12 | The University Of Queensland | Compounds and uses |
| US11370776B2 (en) | 2017-07-07 | 2022-06-28 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as NLRP3 inhibitors |
| UY37848A (es) | 2017-08-15 | 2019-03-29 | Inflazome Ltd | Sulfonilureas y sulfoniltioureas útiles como inhibidores de nlrp3 |
| AU2018317798A1 (en) | 2017-08-15 | 2020-02-13 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as NLRP |
| EP3668840A1 (en) | 2017-08-15 | 2020-06-24 | Inflazome Limited | Novel sulfonamide carboxamide compounds |
| KR20200041337A (ko) | 2017-08-15 | 2020-04-21 | 인플라좀 리미티드 | 신규한 설폰아마이드 카복스아마이드 화합물 |
| WO2019034693A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3 |
| EP3707134A1 (en) | 2017-11-09 | 2020-09-16 | Inflazome Limited | Novel sulfonamide carboxamide compounds |
| WO2019166628A1 (en) | 2018-03-02 | 2019-09-06 | Inflazome Limited | Novel compounds |
| WO2019166619A1 (en) | 2018-03-02 | 2019-09-06 | Inflazome Limited | Novel compounds |
| US11530200B2 (en) | 2018-03-02 | 2022-12-20 | Inflazome Limited | Compounds |
| EP3759090A1 (en) | 2018-03-02 | 2021-01-06 | Inflazome Limited | Novel compounds |
| WO2019166627A1 (en) | 2018-03-02 | 2019-09-06 | Inflazome Limited | Novel compounds |
| GB201806578D0 (en) | 2018-04-23 | 2018-06-06 | Inflazome Ltd | Novel compound |
| CA3104199A1 (en) | 2018-07-20 | 2020-01-23 | F. Hoffmann-La Roche Ag | Sulfonylurea compounds as inhibitors of interleukin-1 activity |
| GB201817038D0 (en) | 2018-10-19 | 2018-12-05 | Inflazome Ltd | Novel processes |
| JP2023500925A (ja) * | 2019-11-07 | 2023-01-11 | インフレイゾーム リミテッド | 神経炎症または炎症性脳疾患の処置および予防 |
| WO2021089781A1 (en) * | 2019-11-07 | 2021-05-14 | Inflazome Limited | Treatment or prevention of psychiatric brain disorders using the nlrp3 inhibitor n-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1 -isopropyl-1 h-pyrazole-3-sulfonamide |
| GB201916237D0 (en) * | 2019-11-07 | 2019-12-25 | Inflazome Ltd | Novel treatment |
| CN114641287A (zh) * | 2019-11-07 | 2022-06-17 | 英夫拉索姆有限公司 | 神经退行性病症的治疗和预防 |
| EP4054564A1 (en) * | 2019-11-07 | 2022-09-14 | Inflazome Limited | Treatment of autoinflammatory disorders |
| WO2021089776A1 (en) * | 2019-11-07 | 2021-05-14 | Inflazome Limited | Treatment and prevention of a traumatic brain disorder |
| WO2022023907A1 (en) | 2020-07-31 | 2022-02-03 | Novartis Ag | Methods of selecting and treating patients at elevated risk of major adverse cardiac events |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4802908A (en) * | 1987-01-22 | 1989-02-07 | E. I. Du Pont De Nemours And Company | Herbicidal 2-(1H)-pyrazinones |
| WO2001019390A1 (en) * | 1999-09-14 | 2001-03-22 | Pfizer Products Inc. | Combination treatment with il-1ra and diaryl sulphonyl urea compounds |
| EP2781216A1 (en) * | 2011-09-02 | 2014-09-24 | Kyowa Hakko Kirin Co., Ltd. | Chemokine receptor activity regulator |
| WO2016131098A1 (en) * | 2015-02-16 | 2016-08-25 | The University Of Queensland | Sulfonylureas and related compounds and use of same |
Family Cites Families (7)
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|---|---|---|---|---|
| FR3046933B1 (fr) | 2016-01-25 | 2018-03-02 | Galderma Research & Development | Inhibiteurs nlrp3 pour le traitement des pathologies cutanees inflammatoires |
| JP2019512009A (ja) | 2016-02-16 | 2019-05-09 | ザ・ユニバーシティ・オブ・クイーンズランド | スルホニルウレアおよび関連化合物ならびにこれらの利用 |
| MA44729A (fr) | 2016-04-18 | 2021-05-12 | Novartis Ag | Composés et compositions pour traiter des états associés à une activité de nlrp |
| WO2017184604A1 (en) | 2016-04-18 | 2017-10-26 | Ifm Therapeutics, Inc | Compounds and compositions for treating conditions associated with nlrp activity |
| EP3272739A1 (en) | 2016-07-20 | 2018-01-24 | NodThera Limited | Sulfonyl urea derivatives and their use in the control of interleukin-1 activity |
| GB201806578D0 (en) | 2018-04-23 | 2018-06-06 | Inflazome Ltd | Novel compound |
| GB201817038D0 (en) | 2018-10-19 | 2018-12-05 | Inflazome Ltd | Novel processes |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4802908A (en) * | 1987-01-22 | 1989-02-07 | E. I. Du Pont De Nemours And Company | Herbicidal 2-(1H)-pyrazinones |
| WO2001019390A1 (en) * | 1999-09-14 | 2001-03-22 | Pfizer Products Inc. | Combination treatment with il-1ra and diaryl sulphonyl urea compounds |
| EP2781216A1 (en) * | 2011-09-02 | 2014-09-24 | Kyowa Hakko Kirin Co., Ltd. | Chemokine receptor activity regulator |
| WO2016131098A1 (en) * | 2015-02-16 | 2016-08-25 | The University Of Queensland | Sulfonylureas and related compounds and use of same |
| CN107428696A (zh) * | 2015-02-16 | 2017-12-01 | 昆士兰大学 | 磺酰脲和相关化合物及其用途 |
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| GB201806578D0 (en) | 2018-06-06 |
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| CA3097832A1 (en) | 2019-10-31 |
| MX2020011196A (es) | 2020-11-13 |
| PT3606909T (pt) | 2020-07-09 |
| CY1123260T1 (el) | 2021-12-31 |
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