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PROTAC技术作用机制独特
1.PROTAC分子通过其一端的靶蛋白配体（POI Ligand）特异性识别并结合靶蛋白，通过其另一端的E3泛素连接酶配体（E3 Ligase Ligand）特异性识别并结合E3 Ligase；
2.形成P O I - P R O T A C - E3 ligase三元复合体；
3. 在此三元复合体中，靶蛋白POI被E3 ligase泛素化修饰，泛素化修饰了的POI随后被蛋白酶体识别并降解，由此抑制靶蛋白的功能。
PROTAC技术优势- 改变靶点的“不可成药性”（undruggable）PROTAC的作用分子机制是通过泛素-蛋白酶体系统降解靶蛋白，并非通过竞争结合以封闭靶蛋白功能区而发挥蛋白功能抑制作用，因此PROTAC对靶蛋白识别结合区不一定非得是活性区，结合力也不一定必须是高亲和力；这使得一些缺乏高亲和力小分子结合的“不可成药性”靶蛋白变成“可成药性”。
- 高效性传统小分子抑制剂通过竞争结合靶蛋白活性功能域而抑制靶蛋白功能，所需小分子的量往往较大；而PROTAC通过泛素-蛋白酶体系统降解靶蛋白以解除靶蛋白功能，故具有可循环使用性、用量低和高效性的特点。
- 无免疫原性与抗体药物相比，PROTAC不会引发抗药抗体产生。综上，PROTAC已成为药物研发领域的新兴利器，在国内外备受科研单位及药企所追捧。
金沙娱场PROTAC技术服务- 靶标蛋白PROTAC-POI的设计合成金沙娱场汇总了当前流行的热门POI配体，不同组织类型的E3ligase配体，并且建立了含数百种连接分子的linker库。此外，金沙娱场成熟的计算机辅助药物设计技术平台，大大提高PROTAC-POI的设计合成质量。
- PROTAC-POI的体外筛选细胞增殖实验（CCK-8或MTT法）通过细胞增殖实验检测作用机制。
检测HiBiT-IRAK4 过表达 OCI-LY10 细胞中 HiBiT-IRAK4 的降解百分比Western Blot（WB检测法）通过WB实验检测初筛到的PROTAC-POI分子对靶蛋白的降解能力，分析DC50值。
Western Blot检测用 IRAK4 degrader-1理的 OCI-LY10 细胞
IRAK4 degrader-1 是一种基于 Pomalidomide 的CRBN型PROTAC
MG132抑制实验表明IRAK4 degrader-1通过蛋白酶体途径降解IRAK4Tumor cell proliferation inhibition effect testIRAK4 Degrader-1对OCI-LY10细胞的生长抑制作用
ACBI1（BRM 降解剂）以剂量依赖性方式降解 BRM蛋白 - PROTAC-POI的动物体内药效筛选CDX小鼠肿瘤模型将相应癌种细胞系移植到裸鼠或NSG小鼠体内，建立皮下瘤或原位瘤模型，通过口服、灌胃或静脉给药，检测体外筛到的PROTAC-POI对鼠体内肿瘤生长的抑制效果。
Cancer Type Orthotopic Model Orthotopic Model (Luc Cell Line) 胶质母细胞瘤 U87-MG U87-MG-luc 肺癌 NCI-H1650, A549, NCI-H1975, NCI-H460, LLC1 A549-luc, LLC1-luc,NCI-H1975-luc 结肠癌 HCT-116, LoVo HT29-luc 胃癌 Hs 746T 胰腺癌 Mia-Paca 2 Mia-Paca 2-luc 乳腺癌 MDA-MB-231 4T1-luc 卵巢癌 SK-OV-3 SK-OV-3-luc 前列腺癌 PC3 PC-3-luc 肾癌 A498 膀胱癌 UM-UC-3 黑色素瘤 B16-F10-luc 肝癌 H22 骨癌 PDX小鼠肿瘤模型将肿瘤组织以组织块的形式移植到NSG小鼠体内，这些肿瘤组织在NSG小鼠体内保持了原始肿瘤的生物学特征，与临床特征相似度更高。利用PDX小鼠模型检测PROTAC-POI对体内肿瘤生长的抑制效果。癌症类型 细胞系 结肠癌 PDXM-008C, PDXM-016C, PDXM-020C, PDXM-021C, PDXM-057C, PDXM-060C, PDXM-075C, PDXM-076C, PDXM-087C, PDXM-104C, PDXM-095C, PDXM-084C, PDXM-072C, PDXM-069C, PDXM-057C, PDXM-015C, PDXM-002C, 肺癌 PDXM-054Lu, PDXM-050Lu, PDXM-047Lu, PDXM-053Lu, PDXM-028Lu, 胃癌 PDXM-092Ga, PDXM-091Ga, 乳腺癌 PDXM-201B, PDXM-202B, PDX-203B 肝癌 PDXM-211Li, PDXM-212Li 胰腺癌 PDXM-221Pa, PDXM-222Pa 膀胱癌 PDXM-231U, PDXM-232U 淋巴瘤 PDXM-241Ly, PDXM-242Ly - 一站式临床前研究服务PK/PD研究、药学分析、药物代谢动力学研究和安全性评价对动物体内药效检测筛选得到的理想的PROTAC-POI进行PK/PD研究、药学分析、药物代谢动力学研究和安全性评价，并汇总实验结果和材料进行IND申报，以助力客户加快PROTAC-POI药物的研发进程。五种高效雄激素受体 (AR) 降解剂在小鼠中静脉和口服给药的药代动力学 (PK) 数据，其中最优化合物为ARD-2128。PK 数据显示，ARD-2128具有出色的整体 PK 曲线：低清除率 (1.2 mL/min/kg) 和中高稳态分布容积 (Vss为2.7 L/kg)。ARD-2128 按 2 mg/kg 剂量静脉给药后的 T1/2为 27.6 小时，按 5 mg/kg 剂量口服给药后T1/2 为 18.8 小时。ARD-2128 (5 mg/kg) 在小鼠体内达到 67% 的口服生物利用度，通过口服给药有效降低 AR 蛋白并抑制肿瘤组织中的 AR 调节基因，从而有效抑制小鼠肿瘤生长且无毒性迹象。
五种化合物在雄性 ICR 小鼠中的 PK 数据汇总[1]ARD-2128 在小鼠、大鼠、犬、猴和人五种属中的血浆稳定性。数据显示，ARD-2128 在所有五种属中都具有稳定的血浆稳定性。
ARD-2128 在五种属中的肝微粒体中代谢稳定性和血浆稳定性[1]参考文献：[1].Xin Han,et al. Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer.J Med Chem. 2021 Sep9;64(17):12831-12854. doi: 10.1021/acs.jmedchem.1c00882. Epub 2021 Aug 25.
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- 中间体
金沙娱场中间体产品列表 Number Compound Name Purity Inventory 1 4-(methoxycarbonyl)benzyl 1H-indole-4-carboxylate 88.91 5.5 g 2 4-(methoxycarbonyl)benzyl 1H-indazole-4-carboxylate 85.34 4.7 g 3 2-chloro-5-(4-fluorophenyl)thiazole-4-carbonitrile 97.97 2 g 4 2-(5-((3-((2H-tetrazol-5-yl)methoxy)azetidin-1-yl)sulfonyl)-2-ethoxyphenyl)-5-methyl-7-propyl-4a,7-dihydroimidazo[5,1-f][1,2,4]triazin-4(3H)-one 99.28 2 g 5 2-((1-((4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4,4a,7-tetrahydroimidazo[5,1-f][1,2,4]triazin-2-yl)phenyl)sulfonyl)azetidin-3-yl)oxy)acetonitrile 99.76 2 g 6 2-(5-((3-((1H-1,2,3-triazol-4-yl)methoxy)azetidin-1-yl)sulfonyl)-2-ethoxyphenyl)-5-methyl-7-propyl-4a,7-dihydroimidazo[5,1-f][1,2,4]triazin-4(3H)-one 98.86 4.5 g 7 2-(5-((3-aminoazetidin-1-yl)sulfonyl)-2-ethoxyphenyl)-5-methyl-7-propyl-4a,7-dihydroimidazo[5,1-f][1,2,4]triazin-4(3H)-one 98.98 1.5 g 8 methyl 4-(3-(4-(6-((4-cyano-2-fluorobenzyl)oxy)pyridin-2-yl)piperidin-1-yl)prop-1-yn-1-yl)-3-((2-methoxyethoxy)methyl)benzoate 96.43 0.5 g 9 methyl 4-(3-(4-(6-((4-cyano-2-fluorobenzyl)oxy)pyridin-2-yl)piperidin-1-yl)prop-1-yn-1-yl)-3-((4-methoxybutoxy)methyl)benzoate 96.73 0.46 g 10 4-(3-(4-(6-((4-cyano-2-fluorobenzyl)oxy)pyridin-2-yl)piperidin-1-yl)prop-1-yn-1-yl)-3-((2-methoxyethoxy)methyl)benzoic acid 97.16 0.03 g 11 methyl 4-(3-(4-(6-((4-cyano-2-fluorobenzyl)oxy)pyridin-2-yl)piperidin-1-yl)prop-1-yn-1-yl)-3-((3-methoxypropoxy)methyl)benzoate 95.65 0.05 g 12 4-((3-((4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)phenyl)sulfonamido)azetidin-1-yl)methyl)-3-fluoro-N-hydroxybenzamide 95.97 0.2 g 13 methyl 6-(((1-((4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)phenyl)sulfonyl)azetidin-3-yl)amino)methyl)nicotinate \ 0.44 g 14 4-(methoxycarbonyl)benzyl 1H-indole-6-carboxylate 97.47 1.6 g 15 4-(methoxycarbonyl)benzyl 1H-indazole-6-carboxylate 95.72 1.7 g 16 2-(5-((3-((2H-tetrazol-5-yl)methyl)-3-hydroxyazetidin-1-yl)sulfonyl)-2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one 96.12 6 g 17 2,2-dimethyl-4-nitrobutanoic acid \ 2.5 g 18 4-(methoxycarbonyl)benzyl 1H-indole-5-carboxylate 95.04 2.4 g 19 4-(methoxycarbonyl)benzyl 1H-indazole-5-carboxylate 70 3 g 20 2-(5-chloro-2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one 79.236 0.9 g 21 2-(2-ethoxy-5-iodophenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one 98.575 5.3 g 22 2-chloro-8-cyclopentyl-6-iodo-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one 94.943 2.2 g 23 N-(5-(4-aminobutyl)pyridin-2-yl)-5-fluoro-4-(4-methylpiperazin-1-yl)pyrimidin-2-amine 99.207 1.1 g 24 2-chloro-5-fluoro-4-(4-methylpiperazin-1-yl)pyrimidine 93.522 6.1 g 25 4-chloro-5-fluoro-N-(5-nitropyridin-2-yl)pyrimidin-2-amine 87.86 3.4 g 26 4-(3-(5-((4-(3-(dimethylamino)azetidin-1-yl)-5-fluoropyrimidin-2-yl)amino)pyridin-2-yl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile 100 0.12 g 27 4-(3-((5-((5-fluoro-4-(4-methylpiperazin-1-yl)pyrimidin-2-yl)amino)pyridin-2-yl)methyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile 90.453 0.1 g 28 methyl 4-(((1-((4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)phenyl)sulfonyl)azetidin-3-yl)amino)methyl)-3-fluorobenzoate 99.188 16 g 29 2-(5-bromo-2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one 97.927 1.9 g 30 2-(5-amino-2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one 85.65 33.4 g 31 methyl 1-(5-bromopyridin-2-yl)piperidine-4-carboxylate 100 16.2 g 32 3-(2-((3-(4-(ethoxycarbonyl)phenoxy)phenyl)amino)-2-oxoethyl)-1H-indole-2-carboxylic acid 90 310 mg 33 methyl 3'-nitro-[1,1'-biphenyl]-3-carboxylate 92 630 mg 34 3-(2-((3'-(1-methoxyvinyl)-[1,1'-biphenyl]-3-yl)amino)-2-oxoethyl)-1H-indole-2-carboxylic acid 93 270 mg 35 3-(2-((3-(2-(methoxycarbonyl)phenoxy)phenyl)amino)-2-oxoethyl)-1H-indole-2-carboxylic acid 92 150 mg 36 methyl 4,6-dichloropicolinate 100 120 mg 37 (R)-4-(5-chloropyrazolo[1,5-a]pyrimidin-7-yl)-3-methylmorpholine 100 120 mg 38 (S)-4-(3,6-dichloropyridazin-4-yl)-3-methylmorpholine 94 110 mg 39 3-(6-chloro-5-morpholinopyridazin-3-yl)-8-oxa-3-azabicyclo[3.2.1]octane 99 120 mg 40 5-chloro-7-(cyclopropylsulfonyl)pyrazolo[1,5-a]pyrimidine 98 110 mg 41 5-bromopyrazolo[1,5-a]pyridine 100 120 mg 42 (R)-4-(7-iodopyrazolo[1,5-a]pyrimidin-5-yl)-3-methylmorpholine 90 108 mg 43 4-bromo-3,6-dichloropyridazine 90 104 mg 44 (1R,5S)-3-(4-((R)-3-methylmorpholino)-7-(1H-pyrazol-3-yl)imidazo[1,5-b]pyridazin-2-yl)-8-oxa-3-azabicyclo[3.2.1]octane 85 111 mg 45 (1R,5S)-3-(pyrazolo[1,5-a]pyrimidin-5-yl)-8-oxa-3-azabicyclo[3.2.1]octane 95 108 mg 46 4-(3,6-dichloropyridazin-4-yl)-2-methylmorpholine 90 106 mg 47 N-((6-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-4-(2-methylmorpholino)pyridazin-3-yl)methyl)-1H-pyrazole-5-carboxamide 90 133 mg 48 8-chloro-2-morpholino-1,7-naphthyridin-4-ol 90 101 mg 49 3,6-dichloro-4-(piperidin-1-yl)pyridazine 95 105 mg 50 7-benzyl-3-chloroisoquinoline 95 102 mg 51 2-(2,6-dioxopiperidin-3-yl)-5-(4-(hydroxymethyl)piperidin-1-yl)isoindoline-1,3-dione 90 109 mg 52 3-(6-chloro-5-(3,3-dimethylmorpholino)pyridazin-3-yl)-8-oxa-3-azabicyclo[3.2.1]octane 90 133 mg 53 2-(2,6-dioxopiperidin-3-yl)-5-(3-(hydroxymethyl)azetidin-1-yl)isoindoline-1,3-dione 90 112 mg 54 5-(3,6-dihydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidine 90 120 mg 55 N-(2,3-dihydro-1H-inden-4-yl)pivalamide 90 145 mg 56 N-(5-bromo-2,3-dihydro-1H-inden-4-yl)pivalamide 90 130 mg 57 1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbaldehyde 90 119 mg 58 piperidin-4-yl 4-methylbenzenesulfonate hydrochloride 90 126 mg 59 2-(2,6-dioxopiperidin-3-yl)-5-(4-((4-hydroxypiperidin-1-yl)methyl)piperidin-1-yl)isoindoline-1,3-dione 90 103 mg 60 2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione 90 136 mg 61 (R)-4-(5-chloropyrazolo[1,5-a]pyrimidin-7-yl)-3-methylmorpholine 95 103 mg 62 methyl 3'-(methylsulfonyl)-[1,1'-biphenyl]-4-carboxylate 92 516 mg 63 1-(4-([1,1'-biphenyl]-4-yloxy)-2-bromophenyl)ethan-1-one 90 140 mg 64 3-(4-nitrophenoxy)aniline 99 588 mg 65 methyl 3-methyl-1H-indole-2-carboxylate 100 130 mg 66 methyl 6-(pyridin-4-yl)-1H-indole-2-carboxylate 95 310 mg 67 methyl 6-(benzyloxy)-1H-indole-2-carboxylate 91 120 mg 68 4-(3-nitrophenoxy)-1,1'-biphenyl 99 180 mg 69 methyl 7-bromo-4-fluoro-3-(2-methoxy-2-oxoethyl)-1H-indole-2-carboxylate 100 140 mg 70 3-(carboxymethyl)-6-phenethoxy-1H-indole-2-carboxylic acid 97 128 mg 71 methyl 2-amino-[1,1'-biphenyl]-4-carboxylate 96 235 mg 72 4-iodo-3-(trifluoromethyl)-1H-pyrazole 100 170 mg 73 (R)-4-(3,6-dichloropyridazin-4-yl)-3-methylmorpholine 98.28 200 mg 74 3,6-dichloro-N-((5-methylimidazo[1,2-a]pyridin-2-yl)methyl)pyridazin-4-amine 100 114 mg 75 ethyl 5-((tert-butoxycarbonyl)amino)pyrazolo[1,5-a]pyridine-3-carboxylate 98.84 150 mg 76 3-(2,6-difluoro-4-iodopyridin-3-yl)-N-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)propanamide 98.77 185 mg 77 3-(6-chloro-5-(4,4-difluoropiperidin-1-yl)pyridazin-3-yl)-8-oxa-3-azabicyclo[3.2.1]octane 96.34 135 mg 78 (2S,6R)-4-(3,6-dichloropyridazin-4-yl)-2,6-dimethylmorpholine 99.53 670 mg 79 tert-butyl 4-(5-chloropyrazolo[1,5-a]pyrimidin-7-yl)-3,6-dihydropyridine-1(2H)-carboxylate 99.09 820 mg 80 3-(2,4-difluoro-6-iodophenyl)propanoic acid 92.14 1000 mg 81 8-bromo-2,4-dichloro-1,5-naphthyridine 95.72 270 mg 82 methyl 2-amino-4-bromo-3,5-difluorobenzoate 90 2.7 g 83 4-(4-aminophenoxy)benzenesulfonamide 90 755 mg 84 4-((4-chlorophenoxy)methyl)aniline 90 3.97 g 85 3'-amino-[1,1'-biphenyl]-3-sulfonamide 90 4.91 g 86 tert-butyl 4-(3-bromobenzoyl)piperazine-1-carboxylate 90 2.43 g 87 methyl 6-(benzyloxy)-3-(2-methoxy-2-oxoethyl)-1H-indole-2-carboxylate 90 135 mg 88 3-chloro-7-vinylisoquinoline 90 800 mg 89 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione 90 330 mg 90 2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline-1,3-dione 90 520 mg 91 ([1,1'-biphenyl]-3-ylmethyl)triphenylphosphonium bromide 98.5 1.543 g 92 (4-phenoxybenzyl)triphenylphosphonium bromide 97.2 344 mg 93 1-(tert-butyl) 2-methyl 3-formyl-1H-indole-1,2-dicarboxylate 93.5 1.167 g 94 methyl 3-formyl-1H-indole-2-carboxylate 93.2 102 mg 95 2-(2,6-dioxopiperidin-3-yl)-5-methylisoindoline-1,3-dione 86.4 242 mg 96 ((4'-(methoxycarbonyl)-[1,1'-biphenyl]-2-yl)methyl)triphenylphosphonium bromide 94.3 1.215 g 97 methyl 6-formyl-1H-indole-2-carboxylate 95.6 777 mg 98 methyl 3'-nitro-[1,1'-biphenyl]-2-carboxylate 96.5 243 mg 99 methyl (E)-3-(4-(([1,1'-biphenyl]-3-yloxy)methyl)phenyl)-2-azidoacrylate 83.6 221 mg 100 4-(benzyloxy)-2-nitrobenzenediazonium tetrafluoroborate 84.3 1.744 g 101 6-(benzyloxy)-3-(carboxymethyl)-1H-indole-2-carboxylic acid 98.7 230 mg 102 methyl 5-(pyridin-4-yl)-1H-indole-2-carboxylate 100 215 mg 103 methyl 4-amino-5-bromo-1,2-dihydropyridazine-3-carboxylate 99.157 230 mg 104 2-(methoxycarbonyl)-1H-indole-6-carboxylic acid 97.1 222 mg 105 2,4-dichloro-7-methoxy-1,8-naphthyridine 86.6 180 mg 106 3-methylthiomorpholine 1,1-dioxide hydrogen chloride 98.2 200 mg 107 3,3'-(3-iodopyrazolo[1,5-a]pyrimidine-5,7-diyl)bis(6-oxa-3-azabicyclo[3.1.1]heptane) 98.3 100 mg 108 4-([1,1'-biphenyl]-4-yloxy)benzaldehyde 98 160 mg 109 1-(tert-butyl) 2-methyl 6-bromo-1H-indole-1,2-dicarboxylate 100 180 mg 110 methyl 6-bromo-1H-indole-2-carboxylate 89 140 mg 111 methyl 6-([1,1'-biphenyl]-4-yloxy)-1H-indole-2-carboxylate 99 100 mg 112 4-([1,1'-biphenyl]-3-yloxy)benzaldehyde 100 450 mg 113 4-amino-3-nitrobenzaldehyde 98 120 mg 114 3-(carboxymethyl)-1H-indole-2-carboxylic acid 100 130 mg 115 3-(carboxymethyl)-1-isobutylindoline-2-carboxylic acid 100 130 mg 116 4-(3-nitrobenzyl)morpholine 100 250 mg 117 6-chloro-3-fluoro-5-vinylpyridin-2-amine 95 110 mg 118 3-(4-aminophenoxy)benzenesulfonamide 90 11.2 g 119 4-(difluoromethoxy)-3-isopropoxybenzoic acid 86.78 1.981 g 120 2-(3-methylisothiazol-5-yl)isoindoline-1,3-dione 91.94 2.232 g 121 N-((1H-1,2,4-triazol-3-yl)methyl)-2-ethoxybenzamide Molecular Weight: 246.27 87.14 1.025 g 122 3-(benzyloxy)-4-(difluoromethoxy)benzamide 88.43 456 mg 123 4-(3-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(2H-tetrazol-2-yl)propyl)bicyclo[1.1.1]pentan-1-yl)phenol 83.68 419 mg 124 methyl 5-cyanoquinoline-6-carboxylate 98.97 1.298 g 125 6-aminoquinoline-5-carbonitrile 98.09 2.017 g 126 2-ethoxy-N-(prop-2-yn-1-yl)benzamide 99.04 6.228 g 127 7a,9,10,11,12,12a-hexahydro-8H-[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one 100 466 mg 128 (2-fluoro-6-methoxypyridin-3-yl)boronic acid 94.8 1080 mg 129 3-bromo-5-(naphthalen-1-yl)pyridine 96.3 1010 mg 130 ethyl 2-(7-methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl)oxazole-5-carboxylate 97.3 165 mg 131 4-bromo-2-ethoxyphenol 92.71 3470 mg 132 2-(7-methoxy-3H-spiro[benzofuran-2,1'-cyclopentan]-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 97.28 12.182 g 133 2-(8-methoxy-2,2-dimethylchroman-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 87.42 1.372 g 134 5-bromo-2-methoxyphenol 100 2.171 g 135 5-iodo-7-methoxy-3-methyl-3H-imidazo[4,5-b]pyridine 96 168 mg 136 2-bromo-6-fluoro-4-(trifluoromethyl)benzoic acid 100 1.9 g 137 tert-butyl (4-bromo-2,2,5-trifluoro-1-oxido-3-oxo-2,3-dihydro-1l4-benzo[b]thiophen-1-ylidene)carbamate 100 2.2 g 138 5-bromo-8-methoxy-2-(trifluoromethyl)quinoline 96.32 25.961 g 139 5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-amine 95 4.3 g 140 2-(5-amino-3-methyl-1H-pyrazol-1-yl)-6-propylpyrimidin-4(3H)-one 95 1.2 g 141 6-chloro-N-cyclohexyl-2-(pyridin-2-yl)pyrimidin-4-amine 95 4.1 g 142 N-(5-bromoquinolin-8-yl)-4-methylbenzenesulfonamide 90 640 mg 143 3-chloro-6-(methylthio)-N-(tetrahydro-2H-pyran-4-yl)pyrazine-2-carboxamide 95 360 mg 144 3-chloro-N-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)-N-methylbenzamide 95 70 mg 145 N-(3-methyl-1-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-yl)-1H-pyrazol-5-yl)thiazole-2-carboxamide 95 188 mg 146 5-(2-methoxyphenyl)-N-(1-methyl-1H-benzo[d]imidazol-2-yl)-1,3,4-oxadiazol-2-amine 93 132 mg 147 N-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)tetrahydro-2H-pyran-4-carboxamide 95 50 mg 148 N-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)isobutyramide 94 134 mg 149 N-(5-bromoquinolin-8-yl)tetrahydro-2H-pyran-4-sulfonamide 95 72 mg 150 2-(pyridin-2-yl)pyrimidine-4,6-diol 90 4.1 g 151 5-bromo-6-nitroquinoline 90 1.3 g 152 6,7-dimethoxy-2-methylquinazolin-4-ol 100 11.3 g 153 7-(benzyloxy)-6-methoxy-2-methylquinazolin-4-ol 75 3.2 g 154 tert-butyl (S)-3-((7-methoxy-2-methyl-4-(((R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)amino)quinazolin-6-yl)oxy)pyrrolidine-1-carboxylate 97 4.6 g 155 (S)-tetrahydrofuran-3-yl methanesulfonate \ 3.5 g 156 tert-butyl (R)-3-((methylsulfonyl)oxy)pyrrolidine-1-carboxylate \ 28.3 g 157 4-(benzyloxy)-5-hydroxy-2-nitrobenzoic acid 85 9.5 g 158 2-(3-azido-2-hydroxypropyl)isoindoline-1,3-dione 100 1.2 g 159 2-hydroxy-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide 94 136 mg 160 4-(bis(4-methoxybenzyl)amino)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one 99 110 mg 161 4-amino-1-(3-fluoro-4-(pyrrolidin-1-ylmethyl)benzyl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one 98 105 mg 162 4-(2-(dimethylamino)ethoxy)benzonitrile 93 171 mg 163 2-(ethylthio)-1-(4-(pyrrolidin-1-ylmethyl)benzyl)-1H-imidazo[4,5-c]quinolin-4-amine 97 75 mg 164 tert-butyl 4-((5-cyanothiophen-2-yl)methyl)piperazine-1-carboxylate 99 105 mg 165 6-butoxy-1-(4-(pyrrolidin-1-ylmethyl)benzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 100 110 mg 166 ethyl (Z)-4-((phenyldiazenyl)methyl)benzoate 93 135 mg 167 2-(chloromethyl)isoindoline-1,3-dione 90 4.5 g 168 2-(chloromethyl)isoindoline-1,3-dione 90 8.0 g 169 2-(chloromethyl)isoindoline-1,3-dione 90 6.9 g 170 2,2'-(pyridin-2-ylmethylene)diphenol 98 7.4 g 171 2,2'-(pyridin-2-ylmethylene)diphenol 98 1.5 g 172 benzyl(2-bromoethyl)sulfane 90 5.7 g 173 2-(chloromethyl)-1H-benzo[d]imidazole 90 4.28 g 174 5-fluoro-3-nitropicolinonitrile 95 9.7 g 175 5-bromo-3-(1,3-dioxolan-2-yl)-2-fluoropyridine 94 2.28 g 176 4-fluoroquinoline 94 2.9 g 177 2-cyclobutylacetonitrile \ 8.24 g 178 methyl (E)-4-bromo-3-((2-methyl-3-phenylallyl)oxy)benzoate \ 4.295 g 179 (Z)-N-((methylsulfonyl)oxy)acetimidoyl chloride \ 8.44 g 180 3-benzyl-3-methyl-2,3-dihydrobenzofuran-6-carboxylic acid 96 556 mg 181 2-((5-bromo-2-nitrophenyl)amino)-N-(2-hydroxyethyl)acetamide 95 110 mg 182 tert-butyl 4-(cyanomethylene)piperidine-1-carboxylate 95 100 mg 183 potassium (3,5-dimethylisoxazol-4-yl)trifluoroborate 95 19 g 184 methyl 2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindoline-5-carboxylate 90 219.84 mg 185 ethyl (E)-3-(3,5-dichlorophenyl)acrylate 90 1986.44 mg 186 3-(1-oxo-5-vinylisoindolin-2-yl)piperidine-2,6-dione 90 831.19 mg 187 3-(4-methoxybenzyl)imidazolidine-2,4-dione 90 4484.23 mg 188 5-(4-chlorophenyl)-1,3,4-oxadiazol-2-amine 90 39.13 mg 189 2-oxo-2-(pyridin-3-yl)acetic acid 90 1428.28 mg 190 2,2,5-tribromo-2,3-dihydro-1H-inden-1-one 90 1622.07 mg 191 2,5-dibromo-2,3-dihydro-1H-inden-1-one 90 3929.72 mg 192 3-bromopiperidine-2,6-dione 90 321.23 mg 193 (E)-2-styrylthiophene 90 3319.16 mg 194 1-oxo-2,3-dihydro-1H-indene-5-carbonitrile 90 1328.26 mg 195 2-chloro-1-(3-hydroxyazetidin-1-yl)ethan-1-one 95 2.73 g 196 2-((2-cyclopropyl-8-fluoro-6-(4-(2-oxopropyl)piperazin-1-yl)quinolin-4-yl)(ethyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile 95 140 mg 197 2-((2-cyclopropyl-8-fluoro-6-(4-(2-hydroxypropyl)piperazin-1-yl)quinolin-4-yl)(ethyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile 97 75 mg 198 6-bromo-2-cyclopropyl-8-fluoro-N-methylquinolin-4-amine 97 566 mg 199 (9H-fluoren-9-yl)methyl (4-(chloromethyl)-2-methoxybenzyl)carbamate 93 410 mg 200 tert-butyl (R)-(3-(benzyloxy)-2-hydroxypropyl)(2,4-dimethoxybenzyl)carbamate 95 150 mg 201 tert-butyl (R)-(3-(benzyloxy)-2-hydroxypropyl)(2,4-dimethoxybenzyl)carbamate 95 4.28 g 202 N-((4-bromophenyl)sulfonyl)-3-methylbutanamide 95 12.0 g 203 methyl 5-(chloromethyl)-4'-(N-(3-methylbutanoyl)sulfamoyl)-[1,1'-biphenyl]-3-carboxylate 99 1.35 g 204 methyl 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-oxo-4,5-dihydrothiophene-3-carboxylate 98 370 mg 205 methyl 4-(benzyloxy)-2,2-dimethylbutanoate 91 8.65 g 206 N-(3-(((2-chloro-5-iodopyrimidin-4-yl)amino)methyl)pyrazin-2-yl)-N-methylmethanesulfonamide 72 1.44 g 207 benzyl 3,3-difluorocyclobutane-1-carboxylate 80 17.4 g 208 1-chloro-7-methoxyisoquinoline-6-carbonitrile 95 1.36 g 209 methyl 3-bromo-5-(hydroxymethyl)benzoate 98 51.45 g 210 2-methoxybenzyl carbamimidothioate hydrochloride 95 22.13 g 211 tert-butyl 7-(methyl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-azaspiro[3.5]nonane-2-carboxylate 93 1000 mg 212 methyl 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate 100 210 mg 213 2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)aniline 97 900 mg 214 2-methoxy-3-(1-methyl-1H-1,2,4-triazol-5-yl)aniline 95.7 500 mg 215 N-(3-methoxy-1,2,4-thiadiazol-5-yl)-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.5]nonane-1-carboxamide 99 700 mg 216 6-bromo-2-(2,6-dimethylpyridin-4-yl)-3-methyl-1H-indole 95 8.14 g 217 6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine hydrochloride 95 1.05 g 218 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide 93 1.27 g 219 6-bromo-3-(piperidin-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridine 96 648 mg 220 tert-butyl (2-((4-(1-(1-oxo-1,2-dihydroisoquinolin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamido)-6-(trifluoromethyl)pyridin-2-yl)oxy)ethyl)carbamate 95 295 mg 221 tert-butyl (1R,5S)-3-(7-bromo-6-chloro-8-fluoroquinazolin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate 99 780 mg 222 methyl 2-(1,4-dioxaspiro[4.5]decan-8-yl)-5-(6-(trifluoromethyl)picolinamido)-2H-indazole-6-carboxylate 95 35 mg 223 N-(6-(2-hydroxypropan-2-yl)-2-(4-oxocyclohexyl)-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide 90 550 mg 224 tert-butyl 4-hydroxy-2-(methylthio)-5,8-dihydropyrido[3,4-d]pyrimidine-7(6H)-carboxylate \ 6.85 g+8.05 g 225 tert-butyl (5-bromo-2-chloro-4-methylpyridin-3-yl)(tert-butoxycarbonyl)carbamate \ 8.23 g+5.10 g 226 2-((4-chloropyrimidin-5-yl)oxy)-5-fluoro-N,N-diisopropylbenzamide \ 9.62 g 227 tert-butyl (S)-10-bromo-11-chloro-8-(2-isopropylphenyl)-7-oxo-3,4,7,8,13,13a-hexahydropyrazino[2',1':3,4][1,4]oxazepino[5,6,7-de]quinazoline-2(1H)-carboxylate \ 1.47 g 228 tert-butyl (5-bromo-4-chloropyridin-3-yl)(tert-butoxycarbonyl)carbamate \ 5.93 g 229 7-fluoro-8-methylnaphthalen-1-yl trifluoromethanesulfonate \ 13.79 g 230 methyl 2-((4-chloropyrimidin-5-yl)oxy)-5-fluorobenzoate \ 2.87 g 231 7-bromo-5-fluoro-1-(2-isopropylphenyl)quinazoline-2,4(1H,3H)-dione \ 1.1 g 232 6-amino-4-bromo-3-chloro-2-fluorobenzonitrile \ 2.55 g 233 6-amino-4-bromo-3-chloro-2-fluorobenzonitrile \ 2.72 g 234 2-amino-4-bromo-6-fluorobenzonitrile \ 6.2 g 235 2-amino-4-bromo-6-fluorobenzonitrile \ 3 g 236 (R)-(1-((3-methylpyrrolidin-1-yl)methyl)cyclopropyl)methanol \ 0.72 g 237 (1-(morpholinomethyl)cyclopropyl)methanol \ 0.88 g 238 (1-(pyrrolidin-1-ylmethyl)cyclopropyl)methanol \ 9.83 g 239 (E)-1-(4-chloro-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)-1H-benzo[d][1,2,3]triazol-6-yl)-3-(dimethylamino)prop-2-en-1-one \ 0.26 g 240 tert-butyl (tert-butoxycarbonyl)(4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)carbamate \ 1 g 241 7-fluoro-8-methylnaphthalen-1-yl trifluoromethanesulfonate \ 1.7 g 242 methyl 2-((2S,6S)-6-methyl-4-((4-nitrophenyl)sulfonyl)piperazin-2-yl)acetate \ 17 g 243 1-benzyl 4-(tert-butyl) (S)-2-(cyanomethyl)piperazine-1,4-dicarboxylate \ 3.8 g 244 methyl 2-((2S,6S)-6-methyl-4-((4-nitrophenyl)sulfonyl)piperazin-2-yl)acetate \ 5.2 g 245 (S)-1-((benzyloxy)carbonyl)-4-(tert-butoxycarbonyl)piperazine-2-carboxylic acid \ 180 mg 246 benzyl (S)-2-(cyanomethyl)piperazine-1-carboxylate \ 3.7 g 247 2-amino-4-bromo-6-fluorobenzonitrile \ 6.2 g 248 4-bromo-2,6-difluorobenzamide \ 5 g 249 2-amino-3-methyl-5-propylpyrazolo[1,5-a]pyrimidin-7(4H)-one \ 6.8 g 250 1-bromo-8-chloronaphthalene \ 5.18 g 251 8-benzyl-1,3,8-triazaspiro[4.5]decane-2,4-dione \ 1.7 g 252 4-bromo-2,6-difluoro-N-((2-isopropylphenyl)carbamoyl)benzamide \ 3.3 g 253 benzyl (2-chloro-9-isopropyl-9H-purin-6-yl)glycinate \ 0.86 g 254 tert-butyl 4-(3,3-dimethylpiperazin-1-yl)benzoate \ 37.7 g 255 4-(3,3-dimethylpiperazin-1-yl)benzoic acid \ 10 g 256 6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amine \ 15 g 257 methyl 4-(benzyloxy)-5-methoxy-2-nitrobenzoate \ 10 g 258 tert-butyl 4-(4-((benzyloxy)carbonyl)piperazin-1-yl)-2-(methylsulfonyl)-5,8-dihydropyrido[3,4-d]pyrimidine-7(6H)-carboxylate \ 12 g 259 2-(4-fluorobenzyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid \ 25 g 260 benzyl (4-bromo-2-cyanophenyl)carbamate \ 20 g 261 methyl 2-((2R,6R)-6-methyl-4-((4-nitrophenyl)sulfonyl)piperazin-2-yl)acetate \ 75 g 262 methyl 2-((2R,6R)-6-methyl-4-((4-nitrophenyl)sulfonyl)piperazin-2-yl)acetate \ 23 g 263 4-bromo-2,6-difluorobenzamide \ 21.6 g 264 tert-butyl (2-bromo-9-isopropyl-9H-purin-6-yl)glycinate \ 50.5 g 265 6-chloro-2-fluoro-9-isopropyl-9H-purine \ 31.6 g 266 tert-butyl (2-chloro-9-isopropyl-9H-purin-6-yl)glycinate \ 130 g 267 tert-butyl (2-bromo-9-isopropyl-9H-purin-6-yl)glycinate \ 164 g 268 methyl (E)-3-(2-([1,1'-biphenyl]-3-yl)vinyl)-6-bromo-1H-indole-2-carboxylate 90 116 mg 269 3-(carboxymethyl)benzofuran-2-carboxylic acid 90 1.2 g 270 2'-methyl-[1,1'-biphenyl]-3-amine 90 150 mg 271 methyl 3-(2-methoxy-2-oxoethyl)benzofuran-2-carboxylate 90 300 mg 272 4-(o-tolyl)pyridin-2-amine 90 150 mg 273 methyl (E)-6-bromo-3-(4-phenoxystyryl)-1H-indole-2-carboxylate 90 108 mg 274 3-vinyl-1,1'-biphenyl 90 155 mg 275 2-methyl-3'-vinyl-1,1'-biphenyl 90 190 mg 276 1-phenoxy-2-vinylbenzene 101 mg 277 4-(([1,1'-biphenyl]-2-yloxy)methyl)-2-bromobenzoic acid 95 120 mg 278 methyl 3-(2-hydroxyethyl)-1H-indole-2-carboxylate 100 130 mg 279 methyl 2'-amino-[1,1'-biphenyl]-4-carboxylate 95 130 mg 280 3-(carboxymethyl)-1-ethyl-1H-indole-2-carboxylic acid 100 100 mg 281 2-nitro-5-phenoxypyridine 99 130 mg 282 1-(2-bromo-4-((2'-methyl-[1,1'-biphenyl]-3-yl)oxy)phenyl)ethan-1-one 95 100 mg 283 methyl 6-benzyl-1H-indole-2-carboxylate 96 100 mg 284 2-(methoxycarbonyl)-1H-indole-6-carboxylic acid 90 121 mg 285 2-phenoxybenzaldehyde 100 221mg 286 methyl 2-(2-([1,1'-biphenyl]-3-ylamino)-2-oxoethyl)-4-aminobenzoate 90 125 mg 287 methyl 6-hydroxy-3-(2-methoxy-2-oxoethyl)-1H-indole-2-carboxylate 90 140 mg 288 tert-butyl (6-(4-(hydroxymethyl)phenoxy)hexyl)carbamate 90 164 mg 289 tert-butyl (4-(4-(hydroxymethyl)phenoxy)butyl)carbamate 90 329 mg 290 6-((4-((8-aminooctyl)oxy)benzyl)oxy)-3-(4-phenoxyphenethyl)-1H-indole-2-carboxylic acid 90 45 mg 291 6-((4-((8-aminooctyl)oxy)benzyl)oxy)-3-(2-oxo-2-((4-phenoxyphenyl)amino)ethyl)-1H-indole-2-carboxylic acid 90 127 mg 292 5-methyl-2-nitrobenzenediazonium 90 500 mg 293 4'-nitro-[1,1'-biphenyl]-4-ol 94.5 593 mg 294 MC21-1687-033 90 111 mg 295 MC-4034-118 90 122 mg 296 MC211417-126 90 110 mg 297 MC21-1702-023 90 106mg 298 MC21-1702-027 90 110mg 299 MC21-1686-048 90 137mg 300 MC21-1686-033 90 106mg 301 MC21-1659-012 90 105mg 302 MC21-1659-040 90 103mg 303 ((benzyloxy)carbonyl)glycine 100 3 g 304 2-chloro-3-nitro-N-(4-(pyrrolidin-1-ylmethyl)benzyl)quinolin-4-amine 92.7 1 g 305 1-(4-aminobutyl)-2-(methylthio)-1H-imidazo[4,5-c]quinolin-4-amine 99 200 mg 306 ethyl glycinate 98 1.5 g 307 2-(methylthio)-1-((5-(pyrrolidin-1-ylmethyl)quinolin-8-yl)methyl)-1H-imidazo[4,5-c]quinolin-4-amine 98.3 89 mg 308 5-methylquinoline-8-carbonitrile 100 383 mg 309 2-butoxy-6-chloro-N,N-bis(4-methoxybenzyl)-5-nitropyrimidin-4-amine 100 337 mg 310 8-bromo-5-methylquinoline 96.2 314 mg 311 2-(butylthio)-6-chloro-N4,N4-bis(4-methoxybenzyl)pyrimidine-4,5-diamine 94.3 209 mg 312 (2-amino-4-(methoxycarbonyl)phenyl)boronic acid 98.8 157 mg 313 N-(4-(4-amino-2-(methylthio)-1H-imidazo[4,5-c]quinolin-1-yl)butyl)-4-((2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl)cyclohexane-1-carboxamide 91.6 55mg 314 methyl 4-carbamoyl-2-nitrobenzoate 99 185 mg 315 tert-butyl 1-(9H-fluoren-9-yl)-3,7-dioxo-2,11,14-trioxa-4,8-diazaheptadecan-17-oate 98.7 210mg 316 3-nitroquinoline-2,4-diol 99.6 250mg 317 (6-(4-methylpiperazin-1-yl)pyridin-3-yl)methanamine 99.6 200mg 318 tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate 88 141 mg 319 methyl 4-(([1,1'-biphenyl]-3-yloxy)methyl)-2-bromobenzoate 98 350 mg 320 4-(([1,1'-biphenyl]-3-yloxy)methyl)-2-bromo-N-methoxy-N-methylbenzamide 100 300 mg 321 3-(carboxymethyl)-6-(trifluoromethyl)-1H-indole-2-carboxylic acid 94 50 mg 322 6-benzyl-3-(1-carboxyethyl)-1H-indole-2-carboxylic acid 95 60 mg 323 9H-benzo[4,5]imidazo[2,1-c][1,2,4]triazol-3-amine 93 213mg 324 1-(2,4-bis(methoxymethoxy)phenyl)ethan-1-one 95 221 mg 325 (S)-2-((naphthalen-1-yloxy)methyl)oxirane 97 221 mg 326 (R)-2-((naphthalen-1-yloxy)methyl)oxirane 77 206 mg 327 2-allyl-4-nitrophenol 99 210 mg 328 pyrido[2,3-d]pyridazin-8(7H)-one 85 202 mg 329 2-chloro-1H-benzo[d]imidazole-1-carbonitrile 99 221 mg 330 3-(benzylamino)-1,1,1-trifluoropropan-2-ol \ 7.2 g 331 methyl N-(tert-butoxycarbonyl)-O-(tert-butyldiphenylsilyl)-D-serinate \ 8.9 g 332 methyl O-benzyl-N-(tert-butoxycarbonyl)-D-serinate \ 3.6 g 333 2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine \ 6.5 g 334 (tert-butoxycarbonyl)-L-proline \ 8 g 335 tert-butyl piperidin-4-ylcarbamate \ 4.8 g 336 4-(2-fluoropyridin-3-yl)-2-(methylthio)pyrimidine 100 110 mg 337 2-methoxy-5-methyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)aniline 100 200 mg 338 tert-butyl (S)-4-(2-hydroxyquinoxalin-6-yl)-2-methylpiperazine-1-carboxylate 91 115 mg 339 4-methylbenzyl carbamimidothioate 93 120 mg 340 5-bromo-7-methoxy-2-methyl-2H-indazole 100 105 mg 341 2,7-dimethylpyrazolo[1,5-a]pyridine-5-carbonitrile 100 103 mg 342 (S)-6-(3-methylpiperazin-1-yl)benzo[d]thiazole 98 110 mg 343 5-bromo-7-methoxy-1-methyl-1H-indazole 99 102 mg 344 6-bromo-2-methylimidazo[1,2-a]pyrazine 95 150 mg 345 tert-butyl (S)-4-(benzo[d]thiazol-6-yl)-2-methylpiperazine-1-carboxylate 90 202 mg 346 5-bromopyrazin-2-amine 98 150 mg 347 tert-butyl (S)-4-(6-aminopyridazin-3-yl)-2-methylpiperazine-1-carboxylate 99 100 mg 348 7-methoxy-3-nitroquinolin-4-ol 94 105mg 349 2-bromo-6-chloro-4-methylpyridin-3-amine 98 100 mg 350 ethyl 4-chloro-6-fluoro-7-methoxyquinoline-3-carboxylate 98 110 mg 351 N-(4-bromo-2,6-difluorobenzyl)-7-methoxy-3-nitroquinolin-4-amine 100 110 mg 352 6-chloro-2,8-dimethylimidazo[1,2-b]pyridazine 99 113 mg 353 tert-butyl (4-methoxypyridin-2-yl)carbamate 97 100 mg 354 5-bromo-7-methoxy-2-methyl-2H-pyrazolo[3,4-c]pyridine 99 116 mg 355 4-chloro-7-methoxy-3-nitroquinoline 98 150 mg 356 N2-(4-chlorophenyl)-N6-cyclopropyl-3-nitropyridine-2,6-diamine 100 3.0g 357 3-(4-(benzyloxy)phenyl)-4-iodo-1H-pyrazole 100 3.1g 358 ethyl 5-morpholinopyrazolo[1,5-a]pyrimidine-3-carboxylate 91 2.9g 359 6-chloro-2-iodo-N-(4-methoxybenzyl)pyrimidin-4-amine 91.27 4.8g 360 2-methoxy-4-methylbenzoic acid 100 3.1g 361 benzyl 4-(tosyloxy)piperidine-1-carboxylate 100 4.4g 362 5-morpholinopyrazolo[1,5-a]pyrimidine-3-carboxylic acid 100 0.9g 363 3-aminopicolinonitrile 100 1.3g 364 5-bromo-2-methoxy-3-nitrobenzamide 74.48 2.1g 365 ethyl 5-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate 100 1.3g 366 2-(5,6-dichloropyridin-3-yl)acetonitrile 83.61 2.1g 367 2-hydroxy-3-nitrobenzamide 98.9 8.1g 368 4-iodo-3-(4-phenoxyphenyl)-1H-pyrazole 76.69 4.3g 369 5-bromopicolinamide 100 4.6g 370 2-chloro-5-nitropyridin-4-amine 100 4.5g 371 3-aminopicolinamide 97.42 4.9g 372 5-nitroisothiazole-3-carboxylic acid 100 5.2g 373 tert-butyl 3-(2,5-dioxo-4-(pyridin-2-yl)imidazolidin-4-yl)propanoate 100 0.9g 374 7-chloro-1,3,4,5-tetrahydro-2H-benzo[d]azepin-2-one 100 2.6g 375 methyl 6-chloro-4-((3-((2,2,2-trifluoroacetamido)methyl)phenyl)thio)pyridazine-3-carboxylate 100 0.3g 376 3-aminopicolinamide 100 1.0g 377 N-(5-bromo-8-(methylamino)-4a,8a-dihydropyrido[3,4-c]pyridazin-3-yl)cyclopropanecarboxamide 100 0.2g 378 ethyl 5-amino-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate 100 0.8g 379 4-bromo-2-ethoxy-6-nitroaniline 100 2.9g 380 tert-butyl (5-(4-aminopyrimidin-2-yl)thiazol-2-yl)(pent-4-en-1-yl)carbamate 100 2.0g 381 N4-(1-methylpiperidin-4-yl)-5-(trifluoromethyl)benzene-1,2,4-triamine 94 0.9g 382 5-bromo-2-hydroxy-4-methoxynicotinonitrile 84 0.2g 383 1H-indol-4-amine 97.76 5.1g 384 tert-butyl (1-(pyrimidin-2-yl)butyl)carbamate 100 3.0g 385 1-(4-amino-5-nitropyridin-2-yl)piperidin-4-ol 100 0.6g 386 tert-butyl (5-(4-aminopyridin-2-yl)thiazol-2-yl)(pent-4-en-1-yl)carbamate 94 0.6g 387 5-(hydroxymethyl)-2-methylphenol 100 1.7g 388 1-(2-chloro-5H-pyrrolo[2,3-d]pyrimidin-5-yl)propan-1-one 100 0.9g 389 tert-butyl (5-(4-aminopyrimidin-2-yl)thiazol-2-yl)(pent-4-en-1-yl)carbamate 100 2.1g 390 methyl 2-acrylamido-4-((tert-butoxycarbonyl)(2-(tosyloxy)propyl)amino)benzoate 100 0.6g 391 N-(1-(4-bromobenzoyl)piperidin-4-yl)acetamide 100 0.6g 392 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridin-2(1H)-one 100 2.5g 393 4-chloro-3-(6-(2-methyl-6-methylenemorpholino)-1H-imidazo[4,5-c]pyridin-2-yl)-3,4-dihydroquinolin-2(1H)-one 40 1.2g 394 2-methoxy-1-(pyrimidin-2-yl)ethan-1-amine 100 1.3g 395 tert-butyl (2-methyl-1-(pyrimidin-2-yl)propyl)carbamate 100 1.0g 396 cyclohexyl(pyrimidin-2-yl)methanamine 85 3g 397 2,6-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol 85 1.2g 398 8-(aminomethyl)-3-benzyl-2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one 100 0.1g 399 N-(3-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)ureido)pyrimidin-4-yl)amino)-1-methyl-2,3-dihydro-1H-pyrazol-4-yl)acrylamide 100 0.5g 400 2-Aminothiazole 100 1.4g 401 4-(4-cyclohexylpiperazin-1-yl)benzene-1,2-diamine 75 1.1g 402 4-(4-bromo-3-methoxyphenyl)-1-methyl-1H-pyrazole 100 5.0g 403 1-(3-bromopyridin-2-yl)piperidine-4-carbohydrazide 100 1.4g 404 (4-bromophenyl)(3-(hydroxymethyl)cyclopentyl)methanone 100 1.6g 405 3-(3-bromo-2-methoxyphenyl)-1-methyl-1H-1,2,4-triazole 100 5.5g 406 7-bromo-3-methylene-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine 100 1.5g 407 (4-chloro-3-nitrophenyl)dimethylphosphine oxide 100 4.3g 408 4-bromo-9H-pyrido[3,4-b]indole 84 4.4g 409 2-((3-amino-4-nitrophenyl)amino)ethan-1-ol 100 3.9g 410 tert-butyl (1-(3-methylpyridin-2-yl)ethyl)carbamate 100 0.8g 411 2-nitro-5-(2,2,6-trimethylmorpholino)aniline 100 4.2g 412 1-(4-amino-5-nitropyridin-2-yl)azetidin-3-ol 100 0.8g 413 5-(3-bromo-2-methoxyphenyl)-4,5-dihydrooxazole 100 3.7g 414 2-methoxy-5-nitropyridin-4-amine 100 2.9g 415 5-(4-chloro-2-fluoro-5-methoxyphenyl)-1-(difluoromethyl)-2-methyl-1,2-dihydro-3H-pyrazol-3-one 100 2.7g 416 2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenol 100 1.5g 417 N-(4-(1-methoxyvinyl)phenyl)acrylamide 100 1.2g 418 8-(trifluoromethyl)quinazolin-4-ol 59 4.7g 419 ethyl 4-bromothiazole-5-carboxylate 98 3.9g 420 2-methoxy-4-morpholinobenzoic acid 100 108g 421 2-carbamoyl-1-(4-chloro-2-methylphenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate 100 8.1g 422 3-(trifluoromethyl)benzohydrazide 100 8.9g 423 N-(4-bromobenzyl)-2,2,2-trifluoroacetamide 100 10.9g 424 methyl 6-chloro-4-((2-(methylthio)phenyl)amino)nicotinate 100 2.6g 425 4-iodo-2-methoxynicotinaldehyde 78 9.2g 426 2-bromo-3,4-dichloro-5-methyl-6-nitroaniline 100 7.3g 427 4-fluoro-5-morpholinobenzene-1,2-diamine 100 8g 428 7-chloro-4-(4-methoxybenzyl)-2-methyl-5-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-b]pyridine-6-carbaldehyde 93.4 102.1g+37.5g 429 5-bromo-2-methoxy-3-nitrobenzamide 88.5 15.42g 430 4-(benzyloxy)-2-naphthoic acid 92.79 115.1g+52.4g 431 4-bromophenol 100 41.4g 432 7-chloro-2-ethyl-4-(4-methoxybenzyl)-5-oxo-4,5-dihydro-2H-[1,2,3]triazolo[4,5-b]pyridine-6-carbaldehyde 78 161.1g+88.9g 433 methyl 6-chloro-4-((2-(methylthio)phenyl)amino)nicotinate 100 3.9g 434 tert-butyl 3-carbamoylazetidine-1-carboxylate 100 7.6g 435 N-(3-bromobenzyl)-2,2,2-trifluoroacetamide 100 7.5g 436 5-bromothiazol-2-amine 100 43.8g 437 5-bromo-4-iodo-2-methoxynicotinaldehyde 91 6.3g 438 1-(2-chloro-7-(pent-4-en-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)propan-1-one 100 15.1g 439 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- 99 4.4g 440 7-nitro-1-tosyl-1H-indole 95 8.5g 441 methyl 5-methyl-1H-pyrazole-3-carboxylate 100 142.5g 442 2-(4-hydroxy-3-nitrophenyl)acetic acid 100 27.2g 443 7-chloro-2-ethyl-4-(4-methoxybenzyl)-5-oxo-4,5-dihydro-2H-pyrazolo[4,3-b]pyridine-6-carbaldehyde 100 3.4g 444 6-chloro-4-methylpyridazin-3(2H)-one 100 3.6g 445 N-(3-chloro-4-methoxy-2-nitrophenyl)acetamide 100 3g 446 2-fluoro-3-morpholino-6-nitroaniline 80.7 10.7g 447 ethyl 5-morpholinopyrazolo[1,5-a]pyrimidine-3-carboxylate 100 7.4g 448 4-nitro-1H-indole 93 45.3g 449 5-(1-methoxyvinyl)-4-nitro-1H-pyrazole 100 28g 450 tert-butyl (2-methyl-1-(pyridin-2-yl)propyl)carbamate 100 16.9g 451 5-([1,4'-bipiperidin]-1'-yl)-2-nitroaniline 100 7.9g 452 tert-butyl (E)-3-(4-morpholinophenyl)acrylate 99 1753mg 453 2-(5-fluoro-1H-indol-3-yl)-2-oxoacetic acid 99 982mg 454 2-(7-chloro-1H-indol-3-yl)-2-oxoacetic acid 99 484mg 455 2-(7-fluoro-1H-indol-3-yl)-2-oxoacetic acid 99 1006mg 456 2-(5-methoxy-1H-indol-3-yl)-2-oxoacetic acid 99 2001mg 457 tert-butyl (E)-3-(4-(4-methylpiperazin-1-yl)phenyl)acrylate 99 2187mg 458 2-(5-methyl-1H-indol-3-yl)-2-oxoacetic acid 99 807mg 459 2-(7-methyl-1H-indol-3-yl)-2-oxoacetic acid 99 2089mg 460 2-(6-methoxy-1H-indol-3-yl)-2-oxoacetic acid 99 1877mg 461 2-(6-methyl-1H-indol-3-yl)-2-oxoacetic acid 99 924mg 462 2-(5-chloro-1H-indol-3-yl)-2-oxoacetic acid 99 297mg 463 4-(piperidin-1-yl)benzaldehyde 99 1657mg 464 4-morpholinobenzaldehyde 99 1786mg 465 2-(4-methoxy-1H-indol-3-yl)-2-oxoacetic acid 99 2231mg 466 2-(4-chloro-1H-indol-3-yl)-2-oxoacetic acid 99 1729mg 467 5-phenyl-3,4-dihydronaphthalen-1(2H)-one 99 103 mg 468 methyl 6-(benzyloxy)-1H-indole-2-carboxylate 95 121 mg 469 methyl 3-(4-(cyclohexyloxy)phenethyl)-6-methoxy-1H-indole-2-carboxylate 95 100 mg 470 1-allyl-3-(cyclohexyloxy)benzene 90 115 mg 471 methyl 6-phenoxy-1H-indole-2-carboxylate 90 125 mg 472 methyl 6-(3-((tert-butyldimethylsilyl)oxy)propyl)-1H-indole-2-carboxylate 95 130 mg 473 3-vinyl-1,1'-biphenyl 99 105 mg 474 2-(2,6-difluoro-4-(methylthio)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 90 480 mg 475 (3,5-difluorophenyl)(methyl)sulfane 90 220 mg 476 3-(2-bromo-3-methylphenyl)propan-1-ol 90 350 mg 477 3'-bromo-2-methyl-1,1'-biphenyl 90 587 mg 478 methyl 3-(2-hydroxyethyl)-6-methyl-1H-indole-2-carboxylate 90 113 mg 479 1-(benzyloxy)-4-(4-vinylphenoxy)benzene 90 133 mg 480 1-(4-vinylphenyl)piperidine 125 mg 481 phenyl(2-vinylphenyl)methanone 95 265 mg 482 3-(2-(2'-methyl-[1,1'-biphenyl]-3-yl)ethyl)-1H-indole-2-carboxylic acid 98 50 mg 483 3-(3-fluorophenyl)-1-vinylbenzene 90 131 mg 484 2-chloro-1-(3-vinylphenyl)benzene 90 153 mg 485 4-fluoro-1-(3-vinylphenyl)benzene 90 204 mg 486 4-(phenyloxy)-1-(prop-2-enyl)benzene 90 134 mg 487 4-{[3-(benzyloxy)phenyl]oxy}benzene-1-carbaldehyde 90 143 mg 488 phenyl(4-vinylphenyl)methanone 90 118mg 489 methyl 3-[(1E)-2-[3-(3-fluorophenyl)phenyl]vinyl]-1H-indole-2-carboxylate 90 104mg 490 methyl 3-[(1E)-2-[3-(2-chlorophenyl)phenyl]vinyl]-1H-indole-2-carboxylate 90 106mg 491 methyl 3-[(1E)-2-(4-{[3-(benzyloxy)phenyl]oxy}phenyl)vinyl]-1H-indole-2-carboxylate 90 105mg 492 3-[3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propan-1-ol 90 105mg 493 3-(4-bromo-3-methylphenyl)prop-2-yn-1-ol 90 120mg 494 3'-methoxy-2,3,4,5-tetrahydro-1,1'-biphenyl 90 101 mg 495 3-cyclohexylphenol 98 156 mg 496 4-((3-cyclohexylphenoxy)methyl)benzaldehyde 90 182 mg 497 3-cyclohexylaniline 93 156mg 498 ethyl 2-(4-acetylphenyl)acetate 98 186 mg 499 4-(4-cyclohexylphenoxy)benzaldehyde 96 203 mg 500 4-(4-fluorophenoxy)benzaldehyde 99 197 mg 501 methyl (E)-6-(3-((tert-butyldimethylsilyl)oxy)propyl)-3-(2-(2'-methyl-[1,1'-biphenyl]-3-yl)vinyl)-1H-indole-2-carboxylate 95 169 mg 502 2-bromo-5-phenyl-1,2,3,4-tetrahydronaphthalen-1-ol 97 143 mg 503 methyl (E)-3-(3-bromostyryl)-1H-indole-2-carboxylate 99 102 mg 504 methyl (E)-2-azido-3-(4-((3-cyclohexylphenoxy)methyl)phenyl)acrylate 96 118 mg 505 2-methyl-1-nitro-4-phenoxybenzene 96 243 mg 506 methyl 3-(2-(2'-methyl-4-(3-((methylsulfonyl)oxy)propyl)-[1,1'-biphenyl]-3-yl)ethyl)-1H-indole-2-carboxylate 90 56 mg 507 (R)-4-benzyl-3-((S)-2-(3-chloropropyl)pent-4-enoyl)oxazolidin-2-one 90 135 mg 508 (S)-2-(3-chloropropyl)pent-4-en-1-ol 90 110 mg 509 5-allyl-1,3-dioxane 90 120 mg 510 (S)-2-(tetrahydro-2H-pyran-3-yl)acetic acid 90 65 mg 511 methyl 3-(2-(6-(3-hydroxypropyl)-2'-methyl-[1,1'-biphenyl]-3-yl)ethyl)-1H-indole-2-carboxylate 95 100mg 512 methyl 6-bromo-3-(2-ethoxy-2-oxoethyl)-1H-indole-2-carboxylate 100 110mg 513 3'-ethynyl-4-fluoro-2-methyl-1,1'-biphenyl 95 120mg 514 tert-butyl (4-(4-formylphenoxy)butyl)carbamate 100 110mg 515 methyl 6-(3-(3-hydroxypropyl)phenoxy)-1H-indole-2-carboxylate 98 140mg 516 3-(3-hydroxypropyl)phenol 95 120mg 517 4-(4-phenoxyphenoxy)benzaldehyde 96 110mg 518 methyl 6-methyl-1H-indole-2-carboxylate 98 100mg 519 methyl 6-([1,1'-biphenyl]-3-yloxy)-1H-indole-2-carboxylate 100 150mg 520 4-(3-(3-hydroxypropyl)phenoxy)benzaldehyde 94 150mg 521 4-((2'-methyl-[1,1'-biphenyl]-4-yl)oxy)benzaldehyde 100 150mg 522 5-bromo-N-(3-nitrophenyl)pentanamide 95 120mg 523 1-(3-nitrophenyl)piperidin-2-one 100 100mg 524 methyl 6-(4-phenoxyphenoxy)-1H-indole-2-carboxylate 100 100mg 525 3-(carboxymethyl)-7-methyl-1H-indole-2-carboxylic acid 95 100mg 526 1-(3-aminophenyl)piperidin-2-one 95 200mg 527 2-([1,1'-biphenyl]-4-yloxy)-4-fluorobenzaldehyde 95 100mg 528 N-(5-bromo-2,3-dihydro-1H-inden-4-yl)pivalamide 100 100 mg 529 3-(6-chloro-5-((R)-3-methylmorpholino)pyridazin-3-yl)-8-oxa-3-azabicyclo[3.2.1]octane 95 230 mg 530 3-(6-chloro-5-(3,3-dimethylmorpholino)pyridazin-3-yl)-8-oxa-3-azabicyclo[3.2.1]octane 96 220 mg 531 5-(2-fluoropyridin-4-yl)-2,3-dihydro-1H-inden-4-amine 85 372 mg 532 (R)-4-(7-iodopyrazolo[1,5-a]pyrimidin-5-yl)-3-methylmorpholine 93 100 mg 533 4-bromo-3,6-dichloropyridazine 99 515 mg 534 3,6-dichloro-4-(piperidin-1-yl)pyridazine 98 204 mg 535 3-ethyl 5-methyl 6-bromoimidazo[1,2-a]pyridine-3,5-dicarboxylate 91 151 mg 536 (1R,5S)-3-(pyrazolo[1,5-a]pyrimidin-5-yl)-8-oxa-3-azabicyclo[3.2.1]octane 96 136 mg 537 3-ethyl 5-methyl 8-bromoimidazo[1,2-a]pyridine-3,5-dicarboxylate 95 313 mg 538 N-(2,3-dihydro-1H-inden-4-yl)pivalamide 100 100 mg
