Table 2. Overview on patent activities in the AC field with emphasis on mAC inhibitors.

Indication	Patent Titles	Key Patents and Applications	Proposed Use of AC-Inhibitors	AC inhibitors/compounds (name listed as written in patent)
Senescence	Signals and molecular species involved in senescence	WO2009139511 US7482134	Detection of cellular senescence Regulation of cellular senescence	2′,5′-Dideoxyadenosine Cis-N-(2-phenylcyclopentyl) azacyclotridec-1-en-2-amine 9-(Tetrahydro-2′-furyl)adenine
Heart Disease	Treatment of cardiac disease including heart attack, myocardial apoptosis, and heart failure, comprises administering type 5 adenylyl cyclase inhibiting compound	WO2009099676	Treatment of cardiac disease including myocardial infarction and heart failure. Regulation of heart rate, contractility, cardiac output and work Regulation of vascular tone Regulation of growth, development or differentiation of vasculature Regulation of growth or character of benign or metastatic neoplasia or tumors	9-Substituted adenine derivatives
	New 9-substituted adenine derivatives are adenylyl cyclase inhibitors used to treat cardiac function and performance and as cytostatics.	WO2002004475 US7045309
Intestinal fluid loss	Treatment of intestinal fluid loss e.g. diarrhea or condition associated with increased 3′-5′-adenosine monophosphate levels involves administering composition comprising e.g. cycloalkenone derivatives, and tricyclic and bicyclic derivatives	WO2001094369 US20020188016 US20020032228 EP1353664	Treating or preventing intestinal fluid loss resulting from bacterial infection (B. anthracis, V. cholerae, E. coli, B. pertussis, Y. pestis) Inhibiting smooth muscle contraction	Cycloalkenone derivatives Tricyclic carboxylic acid derivatives Tricyclic derivatives Bicyclic derivatives Benzene derivatives Biphenyl derivatives 4-{[1-Anthracen-9-yl-meth-(E)-ylidene] -amino} -2-hydroxy-benzoic acid
Fibropro-liferative vasculopathy	New adenine derivatives, used to treat e.g. chronic allograft rejection, vascular restenosis, congestive heart failure, psoriasis, tumor growth, diabetic retinopathy and arteriosclerosis, are adenyl cyclase inhibitors	WO2002040481 US6887880	Prevention of fibroproliferative vasculopathy following vascular injury or a vascular surgical operation Prevention of chronic allograft rejection or vascular restenosis following vascular trauma Measuring the inhibition of adenylyl cyclase activity Treatment of congestive heart failure.	Adenine derivatives
Circadian Rhythm	Use of composition comprising inhibitor of adenylyl cyclase (e.g. purine site inhibitor) for elongation of circadian rhythm and for treating e.g. jet lag, familial advanced sleep phase syndrome and shift lag	WO2007135387	Prolongation of circadian rhythm in Familial Advanced Sleep Phase Syndrome	9-(Tetrahydrofuryl)-adenine 9-(Cyclopentyl) adenine 2′,5′-Dideoxyadenosine
Wound healing	Pharmaceutical composition useful for promoting wound healing in mammals, preferably humans, comprises adenylyl cyclase inhibitor and lysophosphatidic acid inhibitor	WO2010126260	Promotion of wound healing	SQ 22,536 (9-(tetrahydro-2-furanyl)-9H-purin-6-amine)

We performed a keyword search in the Thompson Innovation patent literature databases including the Derwent World Patents Index (http://www.thomsoninnovation.com/ti/contentsets/patents/). The search term was: CTB=((adenylyl or adenylate) cyclase inhibitor*) OR CTB=(ADCY* inhibitor *) and the date of search was June 5^th, 2011. The initial 247 hits were individually reviewed, the patents dealing with mAC inhibitors were identified, and the information contained therein was condensed and compared according to the criteria of the Table. The usefulness of the patents will be critically determined by the selectivity of the compounds for mACs or specific mAC isoforms relative to other targets. As is outlined in the text and Table 1, specificity of nucleoside-based inhibitors among AC isoforms and off-target effects are a great concern. One prominent example in this regard is SQ 22,536 (also referred to as 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (THFA or 9-THF-Ade)), mentioned in several patents. The different nomenclature of this compound in various publications [13-16,65] may have caused some confusion in the literature regarding compound identity.