Design, synthesis, and biological evaluation of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-pyridyl)carboxamido]morphinan derivatives as peripheral selective μ opioid receptor Agents.

Peripheral selective μ opioid receptor (MOR) antagonists could alleviate the symptoms of opioid-induced constipation (OIC) without compromising the analgesic effect of opioids. However, a variety of adverse effects were associated with them, partially due to their relatively low MOR selectivity. NAP, a 6β-N-4'-pyridyl substituted naltrexamine derivative, was identified previously as a potent and highly selective MOR antagonist mainly acting within the peripheral nervous system.

Structure selectivity relationship studies of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-pyridyl)carboxamido]morphinan derivatives toward the development of the mu opioid receptor antagonists.

Mu opioid receptor antagonists have been applied to target a variety of diseases clinically. The current study is designed to explore the structure selectivity relationship (SSR) of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-pyridyl)carboxamido]morphinan (NAP), a lead compound identified as a selective mu opioid receptor antagonist based on the previous study. Among a series of NAP derivatives synthesized, compounds 6 (NMP) and 9 (NGP) maintained comparable binding affinity, selectivity and efficacy to the lead compound.

Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease and conditions such as ischemic stroke affect millions of individuals annually and exert an enormous financial burden on society. A hallmark of these conditions is the abnormal loss of neurons. Currently, there are no effective strategies to prevent neuronal death in these pathologies.

(Z)-3-[(E)-3-Phenyl-allyl-idene]indolin-2-one.

The title compound, C(17)H(13)NO, synthesized to be tested for neuroprotective activities, consists of an indoline and a phenyl-allyl-idene unit with a dihedral angle of 9.0 (1)° between the two ring systems. There are two independent mol-ecules in the asymmetric unit which are connected into a dimer by inter-molecular N-H⋯O hydrogen bonds.

(E)-5-Bromo-3-(2,6-dichloro-benzyl-idene)indolin-2-one.

The title compound, C(15)H(8)BrCl(2)NO, crystallizes with two independent mol-ecules in the asymmetric unit. The dihedral angles between the two aromatic rings are 62.74 (9) and 63.

Synthesis and structure-activity relationship studies of 3-substituted indolin-2-ones as effective neuroprotective agents.

Neurodegenerative diseases are a major health problem particularly among the elderly. Drugs to prevent or slow down the death of neurons are urgently needed but are currently unavailable. We previously reported that the c-Raf inhibitor, GW5074 {5-iodo-3-[(3',5'-dibromo-4'-hydroxyphenyl) methylene]-2-indolinone}, is protective in tissue culture and in vivo paradigms of neurodegeneration.

(Z)-5-Fluoro-3-[(1H-pyrrol-2-yl)methyl-ene]indolin-2-one.

The title compound, C(13)H(9)FN(2)O, a potential neuroprotective agent, consists of an indolinone and a pyrrolyl unit [dihedral angle between the ring planes = 4.9 (1)°]. An intra-molecular hydrogen bond between the carbonyl O atom and the NH group of pyrrole correlates with the Z arrangement of the substituents at the C=C bond.

(E)-5-Chloro-3-(2,6-dichloro-benzyl-idene)-indolin-2-one.

There are two independent mol-ecules of the title compound, C(15)H(8)Cl(3)NO, in the asymmetric unit. Both form inversion dimers via pairs of hydrazide-carbonyl N-H⋯O hydrogen bonds.