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Biomedical subjects

R W Fleming

Publications and source records attributed to R W Fleming.

At least 19 recordsLinked to original sources
PubMed1991

Synthesis and antiarrhythmic activity of alpha-[(diarylmethoxy)methyl]-1-piperidineethanols.

A series of alpha-[(diarylmethoxy)methyl]-1-piperidineethanols was evaluated for antiarrhythmic activity in the coronary artery ligated dog model. Structure-activity relationship studies indicated that the 2,6-dimethylpiperidine group afforded the best antiarrhythmic agents in this series and was essential for long duration of action. This investigation indicated that quaternary ammonium salts were not essential for a long duration of action. It was also shown that the antiarrhythmic activity could be separated from the tachycardia frequently caused by this type of agent.

Animals↗
PubMed1991

Synthesis and antiarrhythmic activity of cis-2,6-dimethyl-alpha,alpha-diaryl-1-piperidinebutanols.

A series of alpha,alpha-diaryl-1-piperidinebutanols was evaluated for antiarrhythmic activity in the coronary ligated dog model. Structure-activity relationship studies indicated that the 2,6-dimethylpiperidine group yielded compounds with the best antiarrhythmic profiles in this series. The length of the methylene chain separating the diarylcarbinol and the amino group was not crucial. Substitution of a hydrogen or a number of functional groups for the hydroxyl group had little effect on efficacy or duration but yielded compounds that produced severe tachycardias. Replacement of one of the aryl groups by hydrogen or a pyridinyl or cyclohexyl group had little effect on efficacy but decreased the duration of action. Compound 18 (pirmenol) was ultimately chosen for further studies and is now being investigated in man.

Animals↗
PubMed1986

Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity relationships for non-sulfhydryl and sulfhydryl types.

The synthesis and angiotensin converting enzyme (ACE) inhibiting activities of quinapril (CI-906, 22), its active diacid (CI-928, 33), and its dimethoxy analogue (CI-925, 25) are reported. These tetrahydro-3-isoquinolinecarboxylic acid derivatives possess equivalent in vitro potency and in vivo efficacy to enalapril. Sulfhydryl analogues with the same structural variation are also highly potent. In contrast, tetrahydro-1-isoquinolinecarboxylic acid and homologous isoindoline-1-carboxylic acid analogues show a striking divergence in potency between the two types, sulfhydryl analogues being essentially inactive, while non-sulfhydryl analogues are equipotent with the proline prototype. This is the first evidence suggesting that alternate binding modes may exist for the two major structural classes of small molecule ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Antihypertensive activity of 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives. 2. 7-Acyl amide analogues.

The effect of acylation with a variety of acids on the antihypertensive activity of 6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidine-7-amine (1) is reported, and structure-activity relationships are discussed. Although several of the compounds show good oral antihypertensive activity in the conscious, spontaneously hypertensive rat (SHR), their activity profile appears to differ from 1 in that the onset of action is shortened at comparable blood pressure lowering doses, and the magnitude of effect is considerably greater at higher doses. A variety of urea, thiourea, guanidine, and amidine analogues also were prepared. Although many of these derivatives showed some antihypertensive effects when dosed orally to SHR, this activity was weaker and of shorter duration than that obtained with 1. Aqueous solubilities and hydrolytic stabilities for four of the more active compounds were measured and suggest that these do not function as prodrugs of 1.

Animals↗
PubMed1981

Short vs long scalp flaps in the treatment of male pattern baldness.

Hair transplantation has been used to restore the bald pate for 25 years. The dissatisfaction of some physicians and patients with the difficulty in obtaining natural density and the length of time necessary to achieve cosmetically acceptable coverage has been a stimulus to the development of scalp flap surgery. The flaps have the advantage of transferring large amounts of hair that give immediate and continuous coverage, normal density, and an improved hairline. Surgeons have applied this technique to areas affected by disease and trauma, as well as male pattern baldness. There are differences between the short temporoparietal flaps and the larger Juri flaps with regard to patient selection, planning, design, technique, complications, and most importantly, results.

Age Factors↗
PubMed1981

Antihypertensive activity of 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives.

A series of 51 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives was prepared and evaluated for antihypertensive activity in the conscious spontaneously hypertensive rat. A number of these compounds, notably 6-(2,6-dichlorophenyl)-2-methylpyrido[2,3-d]pyrimidin-7-amine (36), lowered blood pressure in these rats in a gradual and sustained manner to normotensive levels at oral doses of 10-50 mg/kg. Normalized blood pressure levels could then be maintained by single daily oral doses. The effect of structural variation in the 6-aryl group and in the 2 and 4 positions of the pyridopyrimidine ring on activity is reported and discussed.

Animals↗
PubMed1979

Rhinoplasty record and retrieval system.

The rhinoplastic surgeon must vary technique to fit the anatomic variations of nose and face. Our system to record and correlate preoperative findings with surgical methods could help accomplish this. It includes three forms to record pertinent findings of the history and physical examination, operative findings and techniques, and postoperative evaluations. These forms are numerically coded, and data can be transferred to a punch card system or computer cards for quick and easy retrieval and statistical analysis. The system tries to simplify the many anatomic and surgical variations, yet remain complete. We hope that this system, which has been used in other disciplines, can be applied to rhinoplasty. In this way, more scientific statistical data can be used to support surgical approaches.

Adult↗
PubMed1977

Bis-basic-substituted polycyclic aromatic compounds. A new class of antiviral agents. 8. Bis-basic derivatives of carbazole, dibenzofuran, and dibenzothiophene.

A series of bisalkamine esters, bis-basic ethers, and bis-basic ketones of carbazole, N-ethylcarbazole, dibenzofuran, and dibenzothiophene was synthesized and evaluated for antiviral activity. The series also included two bis-basic alkanes of N-ethylcarbazole and one bis-basic carboxamide of dibenzofuran. Structure-activity relationships indicated that within the carbazole and N-ethylcarbazole series the bisalkamine esters gave the most active derivatives while the bis-basic ketone derivatives of dibenzofuran and dibenzothiophene afforded the more potent compounds within the respective series. The [6,5,6]heterocyclic nuclei were compared with the [6,5,6] aromatic nuclei (fluroene and fluoren-9-one) including tilorone with respect to antiviral activity against encephalomyocarditis (EMC) virus. Maximum activity was associated with the bis-basic ketone side chain and fluoren-9-one nucleus.

Animals↗
PubMed1976

Bis-basic-substituted polycyclic aromatic compounds. A new class of antiviral agents. 7. Bisalkamine esters of 9-oxoxanthene-2,7-dicarboxylic acid, 3,6-bis-basic ethers of xanthen-9-one, and 2,7-bis(aminoacyl)xanthen-9-ones-xanthenes, and -thioxanthenes.

3,6-Bis[2-(dimethylamino)ethoxy]-9H-xanthen-9-one dihydrochloride (4, RMI 10874DA) and 1,1'-(9H-xanthene 2,7-diyl)bis[2-(dimethylamino)ethanone] dihydrochloride (16, RMI 11513DA) were found to prolong survival of mice infected with lethal challenges of encephalomyocarditis (EMC) virus. They were effective by oral as well as subcutaneous administration and showed broad-spectrum antiviral activity. They were selected for preclinical evaluation from the five series of compounds named in the title that were synthesized in analogy to tilorone and related fluorenone derivatives, described earlier. In addition to 4 and 16, compounds 11, 12, 17, and 18 showed high antiviral activity on oral as well as subcutaneous administration. High antiviral activity on subcutaneous admistration was found in the bisalkamine esters 1,2, and 14, the bis(aminoacyl)xanthenes 23 and 26, the bis(aminoalkylene)xanthene 31, the bis(aminoacyl)thioxanthenes 34-40, and the bis-basic ethers of 9-benzylide-nexanthenes 41 and 42. Structure-activity relationships showed a decrease of oral activity with increased length of side chains and increased molecular weight of dialkylamino substituents of 3,6-bis-basic ethers of xanthen-9-one and of 2,7-bis(aminoacyl)xanthenes and-xanthen-9-ones. At least one carbonyl or alkenyl function in conjugation to the xanthene nucleus either at the 9 position of the nucleus or in the side chains is required for high antiviral activity.

Administration, Oral↗
PubMed1975

Participation by internists in primary care; Results of a survey of Mayo clinical alumni.

In late 1972, a survey of Mayo Graduate School alumni was undertaken to determine if changes were needed to make the internal medicine residency program more relevant to such medical practice in the 1970s. Responses were obtained from 783 of the 1,109 former residents in internal medicine to whom questionnaries were sent. Althought nearly half of the responders indicated a subspecialty component to their practice,73% indicated they spend more than half of their time in the delivery of parimary car; and additional 15% reported that primary care occupied from 20% to 50% of their professional time. There was agreement that more general internists are needed and that better geographic distribution of physicians would improve health care delivery.

Delivery of Health Care↗