Table 1.

Interactions of representative adenosine derivatives with receptors and transporters. This simplified table indicates the typical contributions of each structural feature to the overall affinity of these nucleosides at the indicated target, with the beneficial gain in binding affinity indicated as +++ > ++ > + > −. Values were determined from several examples and are not necessarily general to all examples.

Structural feature	hA1AR	hA3AR	mA3AR	h5HT2B/2C	hDAT	hNET
References:	62, 35, 72	62, 35, 72	62	58, 62	35, 72	35, 72
Ribose modifications (A vs. B), R1 at 5′
A (N)-methanocarba	+++	+++	+++	+++	+++	+
5′-CONHCH3	+++	+++	+++	++	+++	+
5′-COOMe or 5′-COOEt	++	++a	−	++	+++	+
5′-COOPr	ND	++	+	+	+++	−
5′-COO-i-Pr	ND	+	−	+ (2C)	−	−
5′-COOH	ND	+	−	+	+	−
5′-CONH-(CH2)2-NH2	−	−	−	+	+	−
4′-truncated	+	++a	+	+	−	ND
B 9-riboside (CH2OH)	+++	++	+	++	++	+
Adenine modifications: R2 at C2; R3 at N6
C2-Cl	+++	+++	+++	++	−	−
C2-C≡C-(5-Cl-thien-2-yl)	−	+++	++	+	+++	+
N6-Me	++	+++	++	+	+++	+
N6-Pr	++	+++	++	ND	++	−
N6-CH(cPr)2	+++	++	ND	+++	−	−
N6-CH2Ph	++	+++	+++	++	−	−
N6-(Me)2	−	+	+	++	−	−
1-deaza	+++	+++	++	+	−	−

ND, not determined.

^areduces agonist efficacy.