. Author manuscript; available in PMC: 2017 Sep 23.

Published in final edited form as: Chem Rev. 2015 Nov 9;115(22):12546–12629. doi: 10.1021/acs.chemrev.5b00434

Table 17.

Multiple examples of caspase-1 peptidomimetic inhibitors based on various P3-P2 scaffolds.

Structure	R =	No.	Casp-1 IC₅₀, nM	Casp-3 IC₅₀, nM	Casp-8 IC₅₀, nM	THP-1 IC₅₀, nM	Ref
Reference - PRALNACASAN
	-	77	3.6	1 300	40	190	286

UNSATURATED CAPROLACTAMS
	- H	137	14	> 10000	2160	100	284
	- Me	138	19	> 10000	2688	153
	- CH₂OH	139	22	> 10000	2110	543
	- CH₂NHCOPh	140	2	1698	1085	466
	- CH₂NHCO-3-OMePh	141	1	1079	448	243
	- CH₂NHCO-4-OMePh	142	1	1128	471	95

MONOCYCLIC 8-MEMBERED LACTAMS
	- Ph(2-OMe)	143	38	> 10000	> 10000	246	283
	- Ph(3-OMe)	144	15	> 10000	> 10000	229
	- Ph(3-F)	145	22	> 10000	> 10000	397
	- Piperonyl	146	24	> 10000	> 10000	285
	- N-morpholine	147	44	> 10000	> 10000	224

8,5-FUSED BICYCLIC PEPTIDOMIMETICS
	- Phenyl	148	3.6	1300	40	190	286
	- 3-Chlorophenyl	149	2.3	> 10000	2900	200
	- 1-Naphthyl	150	1	> 10000	66	3
	- 2-Naphthyl	151	< 1	> 10000	390	32
	- 1-Isoquinolyl	152	< 1	> 10000	160	54

8,6-FUSED BICYCLIC PEPTIDOMIMETICS
	- H	153	10	> 10000	384	245	287
	- Me	154	5	> 10000	247	1820
	- COPh	155	7	8070	38	1420
	- SO₂Me	156	6	> 10000	384	174
	- SO₂Ph	157	2	> 10000	106	159
	-H	158	1	> 10000	506	75
	-SO₂Me	159	1	> 10000	283	46
	-SO₂Ph	160	1	> 10000	50	153

THIAZEPINES
	- Phenyl	161	2 300	> 10000	> 10000	3200	285
	- 3-CF₃Phenyl	162	-	-	-	3400
	- 2-Benzo[b]thiphene	163	320	> 10000	8500	1700
	- 1-Isoquinolyl	164	130	> 10000	5000	1400
	- 2-Naphthyl	165	150	> 10000	> 10000	1100

1-(2-ACYLHYDRAZINOCARBONYL)-CYCLOALKYL CARBOXAMIDES
	- m-Methylphenyl	166	430	-	3120	≥2500	178
	- 1-Naphthyl	167	40	-	420	690
	- 2-Naphthyl	168	30	-	2100	500