Developmental Potential for Endomorphin Opioidmimetic Drugs

Table 3

Functional bioactivities of opioid ligands 1, 2, and 19–50.

			GPI		MVD
Nos.	Compounds		IC50 (nM)^a	pA2^b	IC50 (nM)	pA2	Reference
1	H-Tyr-Pro-Trp-Phe-NH2	(EM-1)	4.03	—^c	283	—	[10]
2	H-Tyr-Pro-Phe-Phe-NH2	(EM-2)	6.88	—	344	—	[10]
19	H-Dmt-Pro-Trp-Phe-NH2		0.27	—	>10,000	8.6	[10]
20	H-Dmt-Pro-Phe-Phe-NH2		0.07	—	1.87	—	[9]
21	H-Dmt-Pro-Phe-NH2		2.33	—	113	—	[9]
22	H-Dmt-Pro-Phe-NH-C2H4-Ph		5.03	—	>10,000	7.05	[9]
23	H-Dmt-Pro-Phe-NH-Bzl		22	—	>10,000	7.18	[11]
24	H-Dmt-Pro-Phe-NH-Ph		37.7	—	>10,000	6.94	[11]
25	H-Dmt-Pro-Phe-NH-4-Pyr		11.8	—	>10,000	6.52	[11]
26	H-Dmt-Pro-Phe-NH-3-Pyr		72.8	—	>10,000	6.33	[11]
27	H-Dmt-Pro-Phe-NH-2-Pyr		15	—	>10,000	6.7	[11]
28	H-Dmt-Pro-Phe-NH-1-Nph		0.49	—	5.47	—	[11]
29	H-Dmt-Pro-Phe-NH-3-Qln		9.14	—	>10,000	5.93	[11]
30	H-Dmt-Pro-Phe-NH-5-Qln		0.26	—	0.616	5.88	[11]
31	H-Dmt-Pro-Phe-NH-6-Qln		6.21	—	>10,000	5.41	[11]
32	H-Dmt-Pro-Phe-NH-8-Qln		445	—	2,981	6.14	[11]
33	H-Dmt-Pro-Phe-NH-5-Isq		0.94	—	>10,000	6.12	[11]
34	H-Mmt-Pro-Phe-Phe-NH2		0.924	—	28.7	++^d	[12]
35	H-Emt-Pro-Phe-Phe-NH2		0.623	—	1.08	+^e	[12]
36	H-Imt-Pro-Phe-Phe-NH2		10.6	—	601	+	[12]
37	H-Det-Pro-Phe-Phe-NH2		0.903	—	47.1	+	[12]
38	H-Dit-Pro-Phe-Phe-NH2		299	—	>10,000	ND^f	[12]
39	H-Tmt-Pro-Phe-Phe-NH2		2.31	—	46.4	++	[12]
40	H-Dmt-Pro-Mmp-Phe-NH2		0.16	—	>10,000	6.59	[13]
41	H-Dmt-Pro-^3,5Dmp-Phe-NH2		14.4	—	>10,000	6.77	[13]
42	H-Dmt-Pro-Dmp-Phe-NH2		0.12	—	>10,000	8.15	[13]
43	H-Dmt-Pro-Dmt-Phe-NH2		1.94	—	>10,000	7.06	[13]
44	H-Dmt-Pro-Tmp-Phe-NH2		0.21	—	>10,000	9.05	[13]
45	H-Dmt-Pro-Emp-Phe-NH2		0.17	—	0.51	—	[13]
46	H-Dmt-Pro-Imp-Phe-NH2		0.2	—	5.56	—	[13]
47	[N-allyl-Dmt^1]EM-1		>10,000	8.18	>10,000	7.32	[10]
48	[N-allyl-Dmt^1]EM-2		>10,000	8.59	>10,000	6.32	[10]
49	1,6-bis[N-allyl-Dmt-NH]hexane		>10,000	7.23	>10,000	6.83	[10]
50	3,6-bis[N-allyl-Dmt-NH-propyl]-5-methyl-2(1H)-pyrazinone		>10,000	7.17	>10,000	6.38	[10]

^aIC₅₀ value is the concentration required to 50% inhibition of the electrically induced contraction in a muscle. ^bpA₂ is the negative log of the molar concentration required to double the agonist IC₅₀ value in order to achieve the original response. ^cNot tested. ^d,eAntagonism by CTAP (200 nM) with the percent recovery of electrically evoked contraction: ++, >50%; +, <50%. ^fNot detected.