Discovery of potent cyclic GMP phosphodiesterase inhibitors. 2-Pyridyl- and 2-imidazolylquinazolines possessing cyclic GMP phosphodiesterase and thromboxane synthesis inhibitory activities.

Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2-phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP-PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme than the well-known inhibitor zaprinast.

Humerus varus: a complication of neonatal, infantile, and childhood injury and infection.

Sixteen cases of humerus varus consequent to proximal humeral fracture and osteomyelitis are described. A similar, but variably severe pattern of progressive deformity occurred in all cases. The medial region of the proximal humeral physis usually either developed slowly or failed to develop, whereas the lateral region developed more normally.

Distraction osteogenesis. A comparison of corticotomy techniques.

The left hindlimbs of 15 adult mongrel dogs were lengthened using the Ilizarov external fixator. Five dogs were assigned to each of three separate groups: (I) corticotomy; (II) osteotomy with multiple drill holes and an osteotome; (III) osteotomy with an oscillating saw. Distraction began on postoperative day seven and continued at a rate of 0.

Antiarthritic profile of BF-389--a novel anti-inflammatory agent with low ulcerogenic liability.

BF-389, dihydro-4-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-methyl-2H-1,2- oxazin-3(4H)-one, is a potent, orally active, antiarthritic and analgesic agent with low ulcerogenic potential. A comparison of the activity profiles of BF-389 and naproxen showed similarities in: (1) suppression of developing and chronic adjuvant arthritis (AA); (2) maximal inhibitory response, as shown by the E(max) values in the developing and established AA models; (3) inhibition of bone degenerative changes associated with chronic adjuvant arthritis; and (4) analgesic activity in the acetic acid and phenylquinone writhing assays. Though BF-389 has been shown to be a potent inhibitor of cyclooxygenase, IC50 = 0.

Computer-automated structure evaluation (CASE) of retinoids in teratogenesis bioassays.

The potential usefulness of the retinoids, a large group of synthetic compounds chemically and structurally related to vitamin A, in the treatment of severe dermatologic diseases and in the prophylaxis and therapy against cancer is severely limited because of their potential teratogenicity. CASE analysis of published retinoid data from the hamster teratogenicity assay and the limb bud "spot" culture system has targeted the hydrophobic region of the retinoids as having the greatest effect on the range of potencies studied. In addition, log p's (as calculated by the CASE program) below a certain value appear to unilaterally result in nonteratogenic retinoids in the in vivo hamster assay system.