Etoxeridine (Carbetidine or Wy2039), a piperidine derivative, is a narcotic analgetic.

Epinine or deoxyepinephrine is an active form of Ibopamine, which is used as a cardiovascular agent in congestive heart failure. Epinine is a stimulant of alpha-adrenoceptor activities: alpha-1 and alpha-2. Experiments on pig’s eyes have shown that epinine can be a promising candidate substance for intraoperative (e.g., cataract surgery) intracameral use in humans.

Pentopril (CGS 13945) is a member of a series of l-glutarylindoline-2(S)-carboxylic acid derivatives. Pentopril was evaluated as an inhibitor of a cell-free preparation of angiotensin-converting enzyme (ACE) isolated from rabbit lung. Intravenous administration of incremental doses of pentopril to anesthetized normotensive rats produced a dose-related inhibition of angiotensin I (AI) pressor responses. The onset of inhibition of the A1 pressor response was rapid, and substantial inhibition occurred at 5 min after administration of the ACE inhibitors. Pentopril hydrolyzed in vivo to the biologically active free-acid form of CGS 13934. It was well tolerated in normal volunteers and hypertensive patients. Pentopril was developed for the treatment of both hypertension and congestive heart failure. Pentopril produced little clinical improvement and no biochemical improvement in a patients with rheumatoid arthritis.

Neladenoson bialanate (BAY1067197) is the first oral partial and highly selective A1R agonist that has entered clinical development for the treatment of heart failure. Neladenoson bialanate maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist. Of particular importance in this clinical development is the potential influence of concomitant use of β-blockers as they have the potential to increase the risk of AV conduction abnormalities with A1R agonist treatment. Two small phase 2a pilot studies evaluating the short-term safety of neladenoson bialanate in patients with HFrEF pretreated with β-blockers have recently completed, and the results are pending (ClinicalTrials.gov identifiers: NCT02040233 and NCT01945606). In a small phase 1 trial in healthy volunteers pretreated with the β-blocker metoprolol succinate, a single 50 mg oral dose of neladenoson bialanate administered together with metaprolol succinate was found to be well tolerated. Notably, no higher degree AV block, prolongation of the PR interval, or relevant decreases in heart rate or systemic blood pressure were observed.

Pinometostat, also known as EPZ-5676, is a small molecule inhibitor of histone methyltransferase with potential antineoplastic activity. Upon intravenous administration, EPZ-5676 specifically blocks the activity of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic genes. Epizyme is developing pinometostat, a small molecule inhibitor of DOT1L, for the treatment of patients with MLL-r, a genetically defined acute leukemia. Epizyme is conducting a phase 1 clinical trial in pediatric patients. Epizyme is evaluating preclinical combinations of pinometostat with other anti-cancer agents in MLL-r leukemia. Pinometostat is being developed in collaboration with Celgene. Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the U.S.

Losoxantrone is an anthrapyrazole that induces both single and double strand breaks in DNA and is a potent inhibitor of DNA synthesis. The drug is in clinical trials for the treatment of breast cancer and of prostate cancer that is refractory to androgen ablation. Acute toxicity is negligible. Losoxantrone may be less cardiotoxic than doxorubicin. Up to 40% of patients encounter alopecia. 3% of patients develop congestive heart failure. Losoxantrone had been in phase II clinical trial for the treatment of breast and prostate cancer. However, this development was discontinued.

Furofenac (also known as SAS 650), a drug that has antiplatelet-aggregation activity and anti-inflammatory activity combined with low ulcerogenic power. It was shown that the furofenac mechanism of action involved the modulation of the platelet cyclooxygenase pathway.

Furofenac (also known as SAS 650), a drug that has antiplatelet-aggregation activity and anti-inflammatory activity combined with low ulcerogenic power. It was shown that the furofenac mechanism of action involved the modulation of the platelet cyclooxygenase pathway.