SOTES
39 1
TABLE I
R n 'CRZCON NR~ R" W R'
R
R=
BP b" or mp, OC
Recrystn solvent or nD ( t , " C P
Yield,
56 ... H Benzyl Xanthyl 169-168 Ale-Ac 71 Benzyl Phenyl H 2 Phenyl 124-126 Et20 93 llethyl Allyl H 3 Phenyl 16.5 ( 2 ) 1.5406(22.5) 54 Methyl mA4myl H 4 Phenyl 174 (0.4.5) 1.3210 (22.3) 7 3 .3 Methyl H n-Heptyld ) n-H ep t yl 172 (0.3) 1.4704(23) 72 Benzyl 6 PhenFl Phenyl OH 186- 188 HJO 74 Benzyl Phenyl C1 I Phenyl 96-98 Et20 46 Methyl Phenyl Methoxy 9 Phen y 1 169- 170 Et20 Low l\lethyl 12 1-Saphthyl ... ... 212 (1.6) 0I Phenyl I1 H e 208-210 13 Phenyl 3lK-Sk Low Phenyl H 99-100 14 Phenyl Methyl' Et20 58 114-115 15 Phenyl Phenyl HQ B 71 a All compounds were analyzed for C, H. C: calcd, 74.38; found, 75.02. The hydrochloride had mp 280-285". Anal. Calcd: C, 66.08; H, 6.59. Found: C, 65.78; H, 6.60. We are indebted to Dr. Roger Adams for a supply of n-diheptylacetic acid. e derivative of 2,2-dimethyl-3-ketopiperazine. f A derivative of homopiperazine. 9 A morpholinyl derivative. h 1 l e - A ~= XIeOH;\le?CO, MK = butanone, Sk = Skellysolve B, B = benzene. NO.
R3
1
-
--
TABLEI1
0Lf-m u R
NO.
b
BP (mm) or mp, O C
Recrystn solventC
Yield,
R
Formula
Analyses
16 Cyanomethyl" EA 17 Amhoethyla 18 CHlCOXH, methylene carbamyl 156-158 DbIF 66 Ci IH22C1NS0 C, H 19 COCKI 144-146 Et20 Low CigHjiClNiO .HC1 s 20 C0CHjC1 1.58-160 EtOII-Et20 CigHmCl,. €IC1 C, H 21 COCsHi 126-128 Sk 72 C~~H,SC~NOI C, H 22 CHlCOOC2Hj 222-230(2) T 50 C?iH2,,ClN?02 C, H 23 CHI 110-112 Sk 71 CisH20N,0b C, H 24 CHlCH=CIICeHj 111-112 Sk 54 C,sH,,C1?;2 C , 1% 5 The preparation and physical constants of compounds 16 and 17were reported by 11.Freifelder, J . Am. Chem. SOC., 82, 2386 (1960). Compound 23 contains the xanthyl radical. EA = EtOH, D h I F = dimethylformamide, T = toluene, Sk = Skellysolve B.
T.IBLE111. DECRE:.~SE OF BLOOD CHOLESTEROL Compd
1
2 3 4
5 6 7 15 16 17
18 20 21 24
Calcd dose, mg/kg/day
400 400 87.5 43,s 6 % .i
300 37.5 500 173 200 200 62.3 62. -5 31.2 62.5 62.5 112.3 5 00 500
Triparanol
100
Chlorocyclizine 23
40
10 26
Response,
% increase
%
in liver mt
redn
31 17 17 13 20 41 ,5d 59 8 33 38 53 44 20 21 27 20 8 47 49 27 33 44
.. 8 24 30
..
.. 16 24
25 46 33 2 10 18
..
28
(@-Diethylaminoe thox y) phenyl 1- 1-(p-tolyl) -2- (p-chloropheny1)ethanol (triparanol), a known hypocholesteremic agent, was included in Table I11 as a control. The compounds are reported in Tables 1-111 and were screened by a method previously d e ~ c r i b e d . ~ Experimental Section4 Table 1.-The compounds in this table xere prepared by the acylation of a monosubstituted piperazine by the appropriate acid chloride in a conventional manner. They were purified by distillation or recrystallization from a suitable solvent. Table 11.-These compounds were prepared by the alkylation of a monosubstituted piperazine by a standard procedure. They were purified by distillation or recrystallization from a solvent.
Acknowledgment.-We are indebted to Orville Kolsto and the microanalytical staff for analytical data.
.. 33
.. 4
.. 31
1'3
( 3 ) H. B. Wright, D . A . Dunnipan, and U.Biermacher, J . M e d . Chem.. 7, 113 (1964). (4) Llelting points were taken on a calibrated Hoover capillary melting point apparatus. Where analyses w e indicated only by symbols of the elements analytical results obtained for those elements were within i0.470 of the theoretical I alues.
