Cyril O. Usifoh

Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids

In order to study the influence of the length of the amino acid chain of N,N‐phthaloylamino acid amides as analogues of the former anticonvulsant taltrimide on the seizureantagonizing activity glycine, β‐alanine and γ‐aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine‐derived amides showed a higher activity than the β‐alanine and GABA derivatives in the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration. The activity was comparable to the respective taurine derivatives. The N,N‐phthaloyl‐glycine amides were also active in the MES test upon oral administration to rats. No significant activity was noted in the seizure threshold test with subcutaneous pentylenetetrazole. The ED50 of N,N‐phthaloyl‐glycine ethyl amide (4b) in the MES test upon intraperitoneal administration to mice was 19.1 mg/kg. On a molar basis this activity is comparable to the activity of phenytoin with little toxicity in the rotorod test. In conclusion, N,N‐phthaloyl‐glycine amides might represent promising antiepileptic drugs.

Synthesis and Anticonvulsant Activity of Acetylenic Quinazolinone Derivatives

Acetylenic derivatives of quinazolinones and quinazolinediones were synthesized and evaluated for their anticonvulsant activity. Most compounds displayed seizure‐antagonizing activity in the maximal electroshock test (MES test) in most cases associated with little or no acute neurotoxicity determined in the rotorod test. Only three compounds exhibited significant activity in the seizure threshold test with subcutaneous pentylenetetrazole (scMet test). Based on the ED50 in the MES test, 1,3‐bis‐(prop‐2‐ynyl)‐quinazoline‐2,4‐(1H,3H)‐dione (9a) was about ten‐fold less active than phenytoin or carbamazepine but about as active as mesuximide.

Willingness to pay for three hypothetical malaria vaccines in Nigeria

BACKGROUND Unlike some African countries that have reported a approximately 50% reduction in malaria deaths in recent years, Nigeria has shown no evidence of a systematic decline in malaria burden. An important and sustainable reduction in malaria burden cannot be achieved unless an effective and inexpensive malaria vaccine becomes available. OBJECTIVES The goals of this study were to determine the willingness to pay (WTP) for 3 hypothetical malaria vaccines with different levels of protection (in years), effectiveness, and adverse effects; and to identify factors that influence the price that people are willing to pay in Nigeria. METHODS With the aid of a questionnaire, a contingent valuation method using payment cards was used to elicit WTP values for 3 hypothetical malaria vaccines. Payment cards contained both a description of the features of the vaccine being evaluated and price options. The 3 hypothetical vaccines had the following characteristics: vaccine A was 75% effective, protected for 3 years, and was well tolerated; vaccine B was 85% effective, protected for 6 years, and was less well tolerated than vaccine A; and vaccine C was 95% effective and protected for 12 years, but was the least well tolerated. Participants consisted of a convenience sample of individuals who were at the pharmacy waiting area of the state-owned hospitals located in Benin City and Warri, Nigeria. Every third patient or caregiver who was in the pharmacy to fill a prescription was asked to take part in the study as they waited to see the pharmacist. If consent was not granted, the next person in line was approached to be interviewed. Linear multiple regression analysis and nonparametric Kruskal-Wallis, Mann-Whitney, or chi(2) test was applied in inferential analysis, where necessary, to investigate the effects of sociodemographic factors on WTP. Prices on payment cards were expressed in Nigerian naira (NGN 150.00 approximately US

Anticonvulsant activity of reaction products of 5,5-diphenylhydantoin with substituted methylene bromides.

1.00), but study results were expressed in US dollars. RESULTS A total of 359 individuals aged > or =18 years of 500 who were approached agreed to participate in the study, giving a response rate of 71.8%. Most of the participants (216/359; 60.2%) were women, and 48 of them were pregnant. Most respondents (299/359; 83.3%) had at least one malaria attack within the last year, and 27.3% (98/359) were hospitalized for malaria. The mean WTP for vaccine A was

Studies on quinazolines IX:1 Fluorination versus 1,2-migration in the reaction of 1,3-bifunctionalized amino-2-propanol with DAST

6.77 and that for vaccine B was

Acetylenic chemistry, part XXVI: One-pot synthesis of 1,3-dialkylated derivatives of quinazolinone and its aza-analogue via mitsunobu reaction

6.70. Vaccine C was the least well accepted with a mean WTP of

Acetylenic chemistry, part 20: Ring opening of 3-azaisatoic anhydride with acetylenic amines: Synthesis of pyrido[2,3-d]pyrimidinones

5.06. Respondents were willing to pay significantly more for vaccine A (95% CI,

Acetylene chemistry, part 32: Alkinylation and cyclic rearrangement of theophylline with unsaturated alcohols by Mitsunobu reaction

5.96-

Ebola Virus Epidemic in West Africa: Global Health Economic Challenges, Lessons Learned, and Policy Recommendations

7.57); thus, the WTP was significantly different for the 3 hypothetical malaria vaccines (P < 0.001; Kruskal-Wallis statistic [kw] = 84.304). Dunns multiple comparison test also indicated that the WTP values for vaccines A and B were significantly different from each other (P < 0.05). There was also a significant difference between vaccine A or B versus C (P < 0.001). All workers and those with a higher monthly income were willing to pay significantly more for vaccines A and B, but less for C (P < 0.003). Those who preferred vaccine A (198/359; 55.2%) were willing to back their choice with a higher WTP (P < 0.001). CONCLUSIONS It appears that although malaria is a serious disease, the Nigerian people in this sample preferred and were willing to pay more for a vaccine that was well tolerated, even if its effectiveness and duration of protection against malaria were lower than those of a product that caused severe adverse effects. Interpretation of this study should be guided by the knowledge that differences exist between the study sample and the general population.

Dimerization of Acetylenic Amides

Some derivatives of 5,5‐diphenylhydantoin (phenytoin) were synthesized by the alkylation of phenytoin with substituted methylene bromides. The hydantoins were evaluated for possible anticonvulsant activity in the maximal electroshock (MES)‐ and subcutaneous pentylenetetrazole (ScMet)‐induced seizures and for neurotoxicity in the rotorod test in mice and rats.