Developmental Potential for Endomorphin Opioidmimetic Drugs

Table 4

Functional bioactivities of opioid ligands 51–70.

		GPI		MVD
Nos.	Compounds	IC50 (nM)^a	pA2^b	IC50 (nM)	pA2	Reference
51	Dmt-NH-(CH2)2-NH-Dmt	2,844	—^c	>10,000	5.5	[18]
52	Dmt-NH-(CH2)4-NH-Dmt	5.33	—	>10,000	5.8	[18]
53	Dmt-NH-(CH2)6-NH-Dmt	3.08	—	>10,000	6.1	[18]
54	Dmt-NH-(CH2)8-NH-Dmt	53.7	—	>10,000	6.4	[18]
55	3,6-bis[Dmt-NH-CH2]-5-methyl-2(1H)-pyrazinone	1,695	—	>10,000	6.47	[19]
56	3,6-bis[Dmt-NH(CH2)2]-5-methyl-2(1H)-pyrazinone	12.9	—	>10,000	6.56	[19]
57	3,6-bis[Dmt-NH(CH2)3]-5-methyl-2(1H)-pyrazinone	1.33	—	>10,000	ND^d	[19]
58	3,6-bis[Dmt-NH(CH2)4]-5-methyl-2(1H)-pyrazinone	1.9	—	41.5	ND	[19]
59	3,6-bis[Dmt-Tic-NH-CH2]-5-methyl-2(1H)-pyrazinone	>10,000	ND	>10,000	11.22	[20]
60	3,6-bis[Dmt-Tic-NH(CH2)2]-5-methyl-2(1H)-pyrazinone	>10,000	6.78	>10,000	10.73	[20]
61	3,6-bis[Dmt-Tic-NH(CH2)3]-5-methyl-2(1H)-pyrazinone	7,025	ND	>10,000	10.56	[20]
62	3,6-bis[Dmt-Tic-NH(CH2)4]-5-methyl-2(1H)-pyrazinone	>10,000	ND	>10,000	11.06	[20]
63	3-[Dmt-Tic-NH(CH2)3]-6-[Dmt-Tic-NH(CH2)4]-5-methyl-2(1H)-pyrazinone	>10,000	ND	>10,000	10.6	[20]
64	3-[Dmt-Tic-NH(CH2)4]-6-[Dmt-Tic-NH(CH2)3]-5-methyl-2(1H)-pyrazinone	>10,000	6.95	>10,000	10.47	[20]
65	3-[Dmt-Tic-NH(CH2)2]-6-[Dmt-Tic-NH(CH2)4]-5-methyl-2(1H)-pyrazinone	>10,000	ND	>10,000	10.99	[20]
66	bis[Dmt-Tic-NH]butane	>10,000	6.99	>10,000	10.51	[20]
67	bis[Dmt-Tic-NH]hexane	2,715	ND	>10,000	10.62	[20]
68	bis[Dmt-Tic-NH]decane	5,425	ND	>10,000	10.97	[20]
69	bis[N,N-dimethyl-Dmt-Tic-NH]hexane	>10,000	8.34	>10,000	11.28	[20]
70	3,6-bis[N,N-dimethyl-Dmt-Tic-NH-propyl]-5-methyl-2(1H)-pyrazinone	>10,000	7.71	>10,000	10.42	[20]

^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. ^dNot determined.