2026-03-07_00000005|ligand|10MW

N-Alkyl & N-Aryl Aminopyrazole Spirocarbamates: A Two-Pronged Lead Optimization Strategy to Identify Orally Bioavailable Plasma Kallikrein Inhibitors compound 25 ((3'R)-1'-{(1P)-5-amino-1-[2-(trifluoromethoxy)phenyl]-1H-pyrazole-4-carbonyl}-6-chloro-5-fluorospiro[[3,1]benzoxazine-4,3'-piperidin]-2(1H)-one); X-ray diffraction 1.62Å
Protein #1 275 residues (85% resolved)

KREAEANTGDNSVSTTKTSTRIVGGTNSSWGEWPWQVSLQVKLTAQRHLCGGSLIGHQWVLTAAHCFDGLPLQDVWRIYSGILNLSDITKDTPFSQIKEIIIHQNYKVSEGNHDIALIKLQAPLNYTEFQKPISLPSKGDTSTIYTNCWVTGWGFSKEKGEIQNILQKVNIPLVTNEECQKRYQDYKITQRMVCAGYKEGGKDACKGDSGGPLVCKHNGMWRLVGITSWGEGCARREQPGVYTKVAEYMDWILEKTQSSDGKAQMQSPAHHHHHH

KREAEANTGDNSVSTTKTSTRIVGGTNSSWGEWPWQVSLQVKLTAQRHLCGGSLIGHQWVLTAAHCFDGLPLQDVWRIYSGILNLSDITKDTPFSQIKEIIIHQNYKVSEGNHDIALIKLQAPLNYTEFQKPISLPSKGDTSTIYTNCWVTGWGFSKEKGEIQNILQKVNIPLVTNEECQKRYQDYKITQRMVCAGYKEGGKDACKGDSGGPLVCKHNGMWRLVGITSWGEGCARREQPGVYTKVAEYMDWILEKTQSSDGKAQMQSPAHHHHHH
Non polymer #2 A1C6Z

InChI=1S/C23H18ClF4N5O4/c24-13-6-7-14-17(18(13)25)22(37-21(35)31-14)8-3-9-32(11-22)20(34)12-10-30-33(19(12)29)15-4-1-2-5-16(15)36-23(26,27)28/h1-2,4-7,10H,3,8-9,11,29H2,(H,31,35)/t22-/m0/s1

c1ccc(c(c1)n2c(c(cn2)C(=O)N3CCC[C@]4(C3)c5c(ccc(c5F)Cl)NC(=O)O4)N)OC(F)(F)F
Non polymer #3 MES

InChI=1S/C6H13NO4S/c8-12(9,10)6-3-7-1-4-11-5-2-7/h1-6H2,(H,8,9,10)

C1COCC[NH+]1CCS(=O)(=O)[O-]
Non polymer #4 NAG

InChI=1S/C8H15NO6/c1-3(11)9-5-7(13)6(12)4(2-10)15-8(5)14/h4-8,10,12-14H,2H2,1H3,(H,9,11)/t4-,5-,6-,7-,8-/m1/s1

CC(=O)N[C@@H]1[C@H]([C@@H]([C@H](O[C@H]1O)CO)O)O
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Reference