This invention relates to compounds of Formula I ##STR1## which are useful in association with a pharmaceutical carrier as antiatherosclerotic agents. In addition, various compounds of Formula I are useful inhibitors of cell proliferation.

BACKGROUND OF THE INVENTION 
The present specification provides methods for use of pharmacologically 
active substances. Further the present specification provides novel 
compositions of matter and novel methods of their preparation. 
Atherosclerosis in mammals is a disease characterized by the deposition of 
atherosclerotic plaque on arterial walls. While atherosclerosis exhibits 
many varied forms and consequences, typical consequences of 
atherosclerotic diseases include angina pectoris, myocardial infarction, 
stroke and transient cerebral ischemic attacks. Other forms of 
atherosclerotic diseases include certain peripheral vascular diseases and 
other ischemias (e.g., bowel and renal). 
Medical science now recognizes that certain forms of atherosclerosis may be 
preventable or reversible. Agents capable of preventing or reversing 
atherosclerosis are characterized as exhibiting antiatherosclerotic 
activity. Since serum lipids have a recognized association with 
atherogenesis, an important class of antiatherosclerotic agents are those 
with serum lipid-modifying effects. Serum lipids implicated in 
atherogenesis include serum cholesterol, serum triglycerides, and serum 
lipoproteins. 
With respect to serum lipoproteins, at least three different classes of 
these substances have been characterized; high density lipoproteins 
(HDL's), low density lipoproteins (LDL's), and very low density 
lipoproteins (VLDL's). HDL's are often referred to as alphalipoproteins, 
while LDL's and VLDL's are referred to as betalipoproteins. The 
enhancement of HDL levels (hyperalphalipoproteinemic activity) is 
postulated to have direct antiatherosclerotic effects. See Eaton, R. P., 
J. Chron. Dis 31:131-135 (1978). In contrast, agents which reduce serum 
LDL's and serum VLDL's (hypobetalipoproteinemic agents) are also 
associated with antiatherogenic effects. See Haust, M. D., "Reaction 
Patterns of Intimal Mesenchyme to Injury and Repair in Atherosclerosis", 
Adv. Exp. Med. Biol. 43:35-57 (1974), which postulates that serum LDL is a 
factor in atherosclerotic lesion formation. 
Numerous animal models have been developed for assessing 
antiatherosclerotic activity. Principal among these are models for 
assessing hypolipoproteinemic activity in the rat and antiatherosclerotic 
activity in the Japanese quail. For a description of the operation of the 
hypobetalipoproteinemic rat model, refer to the known methods of Schurr, 
P. E., et al., "High Volume Screening Procedure for 
Lypobetalipoproteinemia Activity in Rats", Adv. Exp. Med. Biol. 67: 
Atherosclerotic Drug Discovery, pp. 215-229, Plenum Press (1975). For a 
description of the Japanese quail model, see Day, C. E. et al., "Utility 
of a Selected Line (SEA) of the Japanese Quail (Corturnic Corturnix 
japonica) for the Discovery of New Anti-Atherosclerosis Drugs", Laboratory 
Animal Science 27:817-821 (1977). 
2-Aminochromones (4H-1-benzopyran-4-ones) are known in the literature. For 
example, the antiallergic activity of 2-aminochromones has been described 
in the literature by Mazzei, Balbi, Ermili, Sottofattori and Roma (Mazzei, 
M., Ballbi, A., Ernili, A., Sottofattori, E., Roma, G., Farmaco. Ed. Sci., 
(1985) 40, 895 and Mazzei, M., Ermili, A., Balbi, A., Di Braccio, M., 
Farmaco. Ed. Sci., (1986), 41, 611; CA 106:18313w). The CNS activity of 
2-aminochromones has also been described (Balbi, A., Roma, G., Ermili, A., 
Farmaco. Ed. Sci., (1982) 37, 582; Ermili, A., Mazzei, M., Roma, G., 
Cacciatore, C., Farmaco. Ed. Sci., (1977), 32, 375 and 713). The nitro 
derivatives of various 2-aminochromones have recently been described 
(Balbi, A., Roma, G., Mazzei, M., Ermili, A., Farmaco. Ed. Sci., (1983) 
38, 784) and Farmaco. Ed. Sci., 41(7), 548-57. 2-Amino-3-hydroxychromones 
are described in DE 2205913 and GB 1389186. 
U.S. Pat. No. 4,092,416 (see also DE 2555290 and CA 87:102383r) discloses 
various benzopyrone derivatives exhibiting anti-allergic activity, 
including 
2-{2-4-(2-methoxyphenyl)-piperazinyl-1!-ethyl}-5-methoxy-4-oxo-4H-1-benzo 
pyran and 
2-{2-4-(2-methoxyphenyl)-piperazinyl-1!-ethyl}-5-(2-hydroxypropoxy)-4-oxo 
-4H-1-benzopyran. 
JA-025657 and JP-259603 descrive various 2-amino-3-carboxamide derivatives 
and 3-phenyl (optionally substituted)-2-aminochromone derivatives as 
useful as oncostatic and immunosuppressive agents. 
The pharmacomodulation of .alpha.-adrenergic blocking agents by a series of 
benzopyrans, including 2-(1-piperidinylmethylene) -4H-1-benzopyran-4-one, 
is described in Eur. J. Med. Chem., 1987, 22(6), 539-44; CA 109:92718k. 
Structurally, the closest compounds in the literature to 
2-(4-morpholinyl)-4H-1-benzopyran-4-one (Cpd 2) is believed to be the 
3-hydroxy, 3-methoxy and 3-acetyloxy analogues (i.e., 
2-(4-morpholinyl)-3-hydroxychromone, 2-(4-morpholinyl) -3-methoxychromone 
and 3-(acetyloxy)-2-(4-morpholinyl)chromone) reported by Eiden and Docher 
(Eiden, F., Dolcher, D., Arch. Pharm. (Weinheim Ger.) (1975) 308, 385) and 
DE 2205913; CA 83(11):96942w and CA79(19):1154408. 
6,7-dimethoxy-2-(4-morpholinyl)chromone is disclosed in J. Chem. Soc., 
Perkins Trans. 1, (2), 173-4; CA78(9);58275v. 
3-Acetyl-2-(4-morpholinyl)chromone is disclosed in Arch. Pharm. 316(1), 
34-42; CA98(15):12915 g. 3-hydroxy-2-4-(2-hydroxyethyl) 
-1-piperazinyl!-4H-1-benzopyran-4-one and 3-hydroxy-2-(4-methyl 
-1-piperazinyl)-4H-1-benzopyran-4-one are disclosed in Arch. Pharm 308(5), 
385-8; CA83(11):96942w. 5,8-dimethoxy-2-(4-methyl 
-1-piperazinyl)-4H-1-benzopyran-4-one is disclosed in J. Heterocycl. 
Chem., 18(4), 679-84; CA95(17):150348v. 
The synthesis of 2-aminochromones from the corresponding 2-sulphonyl and 
2-sulphinyl analogues has been reported by Bantick and Suschitzky 
(Bantick, J. R., Suschitzky, J. L., J. Heterocyclic Chem., (1981) 18, 
679). Also described in this report is the preparation of the HCL and 
H.sub.2 SO.sub.4 salts of several 2-aminochromones. 
The anti-platelet activity of some 2-(dialkylamino)chromones, namely: 
2-(diethylamino)-5,6-dimethyl-4H-1-benzopyran-4-one,2-(diethylamino)-6,7-d 
imethyl-4H-1-benzopyran-4-one,2-(diethylamino)-7-hydroxy-5-methyl-4H-1-benz 
opyran-4-one, 2-(diethylamino)-5-hydroxy-7-methyl-4H-1-benzopyran-4-one, 
2-(diethylamino)-6-chloro-8-isopropyl-4H-1-benzopyran-4-one, 
2-(diethylamino)-5,7-methoxy-4H-1-benzopyran-4-one, 
2-(ethylamino)-5-hydroxy-4H-1-benzopyran-4-one, 
2-(ethylamino)-7-hydroxy-4H-1-benzopyran-4-one, 
2-(diethylamino)-7-hydroxy-6-nitro-4H-1-benzopyran-4-one, 
2-(diethylamino)-4H-1-benzopyran-4-one,2-(dimethylamino)-7-methoxy-4H-1-be 
nzopyran-4-one, 2-(diethylamino)-7-methoxy-4H-1-benzopyran-4-one, 
2-(1-pyrrolidinyl)-7-methoxy-4H-1-benzopyran-4-one, 
2-(1-piperidinyl)-7-methoxy-4H-1-benzopyran-4-one, 
2-(diethylamino)-7-hydroxy-4H-1-benzopyran-4-one, 
2-(1-piperdinyl)-7-hydroxy-4H-1-benzopyran-4-one, 
2-(ethylamino)-7-methoxy-4H-1-benzopyran-4-one, 
2-(diethylamino)-5-hydroxy-4H-1-benzopyran-4-one, 
2-(diethylamino)-5-methyl-8-isopropyl-4H-1-benzopyran-4-one, and 
2-(diethylamino)-3-(4-morpohoinomethyl)-7-methoxy-4H-1-benzopyran-4-one, 
was reported by Mazzei et al. in Eur. J. Med. Chem. 23, 237-242 (May-June 
1988); CA 110:75246h. 
The literature on the use of an ynamine in the synthesis of a 
2-aminochromones has been reported by Tronchet, Bachler and Bonenfant 
(Tronchet, J. M. J., Bachler, B., Bonenfant, A., Helv. Chim. Acta. (1976), 
59, 941). In this report, a 2-amino-3-glycosylchromone was prepared. 
2-Amino-1,3-benzoxazin-4-ones are also known in the literature. 
Specifically, 2-morpholinyl-4H-1,3-benzoxazin-4-one (Cpd98) and 
8-methyl-2-(4-morpholinyl) -4H-1,3-benzoxazin-4-one (Cpd84) are described 
in Netherlands patent application 6,412,966 (see also U.S. Pat. No. 
3,491,092), and in the literature (Grigat, E., Putter, R., Schneider, K., 
Wedemeyer, K., Chem. Ber., (1964) 97, 3036). 
The fungicide and analgesic activity of 2-amino-1,3-benzoxazin-4-ones are 
also claimed by Sankyo in Japn. Tokkyo Koho 79 20,504 (CA 91:157755b) and 
in Japan (Kokai 72, 17,781 (CA 77:140107e). These patents appear to cover 
2-(4-morpholinyl) -4H-1,3-benzoxazin-4-one (Cpd 98) and 6,7-substituted 
-2-(4-morpholinyl) analogues for the above indications. 
The synthesis of 2-dialkylamino-1,3-benzoxazin-4-ones has been described by 
Kokel et al (see Tet. Letters (1984) 3837). 
2-N-Alkyl and 2-N-aryl-1,3-benzoxazin-4-ones have been described by Palazzo 
and Giannola (Palazzo, S., Giannola, L. I., Atti. Accad. Sci. Lett. Arti 
Palermo, Parte 1, (1976) 34(2), 83-7). 
2-Benzamidino-1,3-benzoxazin-4-one have been described by Brunetti, H., and 
Luthi, C. E. (in Helv. Chim. Acta., (1972) 55, 1566). 
PCT/US89/05526, filed 15 Dec. 1989 (published 28 Jun. 1990) discloses 
various 1-benzopyran-4-ones and 2-amino-1,3-benzoxazines-4-ones, including 
2-(4-morpholinyl) -4H-1-benzopyran-4-one, 8-Methyl-2-(4-morpholinyl) 
-(7-phenylmethoxy)-4H-benzopyran-4-one, 7-(1-cyclohexyl 
-1H-tetrazol-5-yl)methoxy!-8-methyl-2-(4-morpholinyl)-4H-1-benzopyran-4-on 
e, 8-Methyl-2-(4-morpholinyl)-7-(2-(1-piperidinyl)ethyl)oxy 
-4H-1-benzopyran-4-one, 
8-Methyl-2-(4-morpholinyl)-7-(2-(1-pyrrolidinyl)ethyl)oxy-4H-1-benzopyran- 
4-one, 7-2-(ethylphenylamino)ethoxy!-8-methyl-2-(4-morpholinyl) 
-4H-1-Benzopyran-4-one, as well as their antiatherosclerotic, 
antithrombotic activity, cell proliferation (inhibitive) and/or inhibitive 
of platelet aggregation. 
BRIEF DESCRIPTION OF THE INVENTION 
This invention relates to compounds of the Formula I which are useful in 
association with a pharmaceutical carrier as antiatherosclerotic agents. 
In addition, various compounds of the Formula I are useful inhibitors of 
cell proliferation and/or platelet aggregation.