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Chemistry

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Also known as: 569-57-3, Tace, Chlortrianizen, Chlortrianisestrol, Chlorotrianisine, Chlorestrolo
Molecular Formula
C23H21ClO3
Molecular Weight
380.9  g/mol
InChI Key
BFPSDSIWYFKGBC-UHFFFAOYSA-N
FDA UNII
6V5034L121

Chlorotrianisene
A powerful synthetic, non-steroidal estrogen.
1 2D Structure

Chlorotrianisene

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
1-[1-chloro-2,2-bis(4-methoxyphenyl)ethenyl]-4-methoxybenzene
2.1.2 InChI
InChI=1S/C23H21ClO3/c1-25-19-10-4-16(5-11-19)22(17-6-12-20(26-2)13-7-17)23(24)18-8-14-21(27-3)15-9-18/h4-15H,1-3H3
2.1.3 InChI Key
BFPSDSIWYFKGBC-UHFFFAOYSA-N
2.1.4 Canonical SMILES
COC1=CC=C(C=C1)C(=C(C2=CC=C(C=C2)OC)Cl)C3=CC=C(C=C3)OC
2.2 Other Identifiers
2.2.1 UNII
6V5034L121
2.3 Synonyms
2.3.1 Depositor-Supplied Synonyms

1. 569-57-3

2. Tace

3. Chlortrianizen

4. Chlortrianisestrol

5. Chlorotrianisine

6. Chlorestrolo

7. Chlorotrianizen

8. Chlortrianisen

9. Chloortrianisestrol

10. Clorotrisin

11. Hormonisene

12. Khlortrianizen

13. Clorestrolo

14. Merbentul

15. Anisene

16. Metace

17. Rianil

18. Chlortrianisoestrolum

19. Chlortrianisene

20. Chlorotrisin

21. Tri-p-anisylchloroethylene

22. Chlortrianisenum

23. Tace-fn

24. Tris(p-methoxyphenyl)chloroethylene

25. Clorotrianiseno

26. Trianisestrol

27. Chlorotrianisenum [inn-latin]

28. Chlorotrianisenum

29. Tace (pharmaceutical)

30. Chlorotris(p-methoxyphenyl)ethylene

31. Clorotrianiseno [inn-spanish]

32. Nsc-10108

33. Ethylene, Chlorotris(p-methoxyphenyl)-

34. Cta

35. 1-[1-chloro-2,2-bis(4-methoxyphenyl)ethenyl]-4-methoxybenzene

36. 1,1',1''-(1-chloro-1-ethenyl-2-ylidene)-tris(4-methoxybenzene)

37. Benzene, 1,1',1''-(1-chloro-1-ethenyl-2-ylidene)tris(4-methoxy)-

38. Chlorotrianisene (inn)

39. 4,4',4''-(2-chloroethene-1,1,2-triyl)tris(methoxybenzene)

40. Mls000028625

41. Chebi:3641

42. Clorotrianisene

43. Triagen

44. Ncgc00016511-02

45. Cas-569-57-3

46. Smr000058658

47. 1-[2-chloro-1,2-bis(4-methoxyphenyl)ethenyl]-4-methoxybenzene

48. 6v5034l121

49. 1,1',1''-(2-chloroethene-1,1,2-triyl)tris[4-(methyloxy)benzene]

50. Dsstox_cid_1299

51. Clorotrianisene [dcit]

52. Dsstox_rid_76067

53. Dsstox_gsid_21299

54. Chlorotrianisene [inn]

55. Benzene, 1,1',1''-(1-chloro-1-ethenyl-2-ylidene)tris(4-methoxy-

56. Benzene, 1,1',1''-(1-chloro-1-ethenyl-2-ylidene)tris[4-methoxy-

57. Ccris 4769

58. Hsdb 3302

59. Sr-01000721940

60. Einecs 209-318-6

61. Tace (tn)

62. Brn 1891845

63. Chlorotrianisene [nonsteroidal Oestrogens]

64. Chlorotrianisene [usp:inn:ban]

65. Prestwick_22

66. Unii-6v5034l121

67. Spectrum_000136

68. 1,1',1''-(2-chloroethene-1,1,2-triyl)tris(4-methoxybenzene)

69. Chlorotrianisene, ~95%

70. Opera_id_1728

71. Prestwick0_000757

72. Prestwick1_000757

73. Prestwick2_000757

74. Prestwick3_000757

75. Spectrum2_000704

76. Spectrum3_000343

77. Spectrum4_000954

78. Spectrum5_000711

79. Schembl8225

80. Bspbio_000774

81. Bspbio_002005

82. Chlorotrianisene [mi]

83. Kbiogr_001568

84. Kbioss_000596

85. 4-06-00-07650 (beilstein Handbook Reference)

86. Mls002415722

87. Spectrum1500181

88. Spbio_000887

89. Spbio_002713

90. Chlorotrianisene [hsdb]

91. Bpbio1_000852

92. Gtpl7146

93. Chlorotrianisene [vandf]

94. Chembl1200761

95. Chlorotrianisene [mart.]

96. Dtxsid1021299

97. Kbio2_000596

98. Kbio2_003164

99. Kbio2_005732

100. Kbio3_001225

101. Chlorotrianisene [who-dd]

102. Hms1570g16

103. Hms1920k17

104. Hms2091c20

105. Hms2097g16

106. Hms2230l03

107. Hms3371e11

108. Hms3714g16

109. Amy40000

110. Bcp13708

111. Hy-b2158

112. Nsc10108

113. Zinc1530598

114. Tox21_110466

115. Tox21_202361

116. Tox21_302897

117. Benzene, 1,1',1'-(1-chloro-1-ethenyl-2-ylidene)tris(4-methoxy)-

118. Ccg-40079

119. S4629

120. Chlorotrianisene [orange Book]

121. Wln: 1or Dyguyr Do1&r Do1

122. Akos015960863

123. Tox21_110466_1

124. Db00269

125. Ncgc00016511-01

126. Ncgc00016511-03

127. Ncgc00016511-04

128. Ncgc00016511-05

129. Ncgc00016511-06

130. Ncgc00016511-08

131. Ncgc00091333-01

132. Ncgc00091333-02

133. Ncgc00091333-03

134. Ncgc00256381-01

135. Ncgc00259910-01

136. Ac-12512

137. Bs-17089

138. Sbi-0051309.p003

139. Db-052990

140. Ab00051941

141. B5912

142. Cs-0020308

143. Ft-0632409

144. A16446

145. C75668

146. D00269

147. 569c573

148. A899783

149. Q5103213

150. Sr-01000721940-2

151. Sr-01000721940-3

152. 1,1',1''(1-chloro-1-ethenyl-2-ylidene)tris[4-methoxybenzene]

153. 1-[2-chloro-1,2-bis(4-methoxyphenyl)vinyl]-4-methoxybenzene #

154. Benzene,1',1''-(1-chloro-1-ethenyl-2-ylidene)tris[4-methoxy-

2.4 Create Date
2005-03-26
3 Chemical and Physical Properties
Molecular Weight 380.9 g/mol
Molecular Formula C23H21ClO3
XLogP36.4
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count3
Rotatable Bond Count6
Exact Mass380.1179222 g/mol
Monoisotopic Mass380.1179222 g/mol
Topological Polar Surface Area27.7 Ų
Heavy Atom Count27
Formal Charge0
Complexity442
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Antineoplastic Agents, Hormonal; Estrogens, Non-Steroidal

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


...REPORTED RELIEF OF DYSMENORRHEA BY INHIBITING OVULATION WITH ESTROGEN. ... USE OF ESTROGENS IN TREATMENT OF ENDOMETRIOSIS... FAILURE OF OVARIAN DEVELOPMENT...IS TREATED WITH ESTROGEN... COMMON FORM OF ACNE IS FEATURE OF PUBERTY... TREATMENT WITH ESTROGEN IS EFFECTIVE... /ESTROGENS/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1432


SENILE OR ATROPHIC VAGINITIS, OFTEN ASSOC WITH CHRONIC INFECTION OF ATROPHIC STRUCTURES, RESPONDS WELL TO ESTROGEN. KRAUROSIS VULVAE, DISTRESSINGLY ITCHY CONDITION DUE IN PART TO DEFICIENCY IN ESTROGEN...IS FAVORABLY INFLUENCED BY ESTROGEN SUPPLEMENTED BY LOCAL TREATMENT... /ESTROGENS/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1432


...UNIQUE IN THAT ITS POTENCY IS GREATER BY ORAL THAN BY ANY OTHER ROUTE...

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 918


For more Therapeutic Uses (Complete) data for CHLOROTRIANISENE (7 total), please visit the HSDB record page.


4.2 Drug Warning

...LONG DURATION OF ACTION MAKES THIS DRUG UNSUITABLE FOR TREATMENT OF MENSTRUAL DISORDERS & OTHER CONDITIONS IN WHICH CYCLIC THERAPY IS DESIRED.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 918


...PREGNANT PT SHOULD NOT BE GIVEN ESTROGENS, PARTICULARLY DURING 1ST TRIMESTER-TIME WHEN FETAL REPRODUCTIVE TRACT IS DEVELOPING & MAY BE INFLUENCED BY EXOGENOUS ESTROGENS. /ESTROGENS/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1429


...IS RELATED TO TRIPARANOL & TO CLOMIPHENE, BOTH OF WHICH CAN PRODUCE CATARACTS IN CERTAIN CIRCUMSTANCES. THIS SEEMS TO BE REASON FOR WATCHING FOR CATARACTS WHEN USING CHLOROTRIANISENE, BUT SO FAR THIS DRUG HAS NOT BEEN DEMONSTRATED TO PRODUCE THEM.

Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 281


4.3 Drug Indication

Used to treat symptoms of menopause, deficiencies in ovary function (including underdevelopment of female sexual characteristics and some types of infertility), and in rare cases, prostate cancer. Chlorotrianisene may also be used to prevent breast engorgement following childbirth.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Chlorotrianisene is a nonsteroidal synthetic estrogen. After menopause, when the body no longer produces estrogen, chlorotrianisene is used as a simple replacement of estrogen. The estrogen-stimulated endometrium may bleed within 48-72 hours after discontinuance of estrogen therapy. Paradoxically, prolonged estrogen therapy may cause shrinkage of the endometrium and an increase in size of the myometrium. Estrogens have a weak anabolic effect and may cause sodium retention with associated fluid retention and edema. Estrogens may also decrease elevated blood cholesterol and phospholipid concentrations. Estrogens affect bone by increasing calcium deposition and accelerating epiphyseal closure, following initial growth stimulation. During the preovulatory or nonovulatory phase of the menstrual cycle, estrogen is the principal determinant in the onset of menstruation. A decline of estrogenic activity at the end of the menstrual cycle also may induce menstruation; however, the cessation of progesterone secretion is the most important factor during the mature ovulatory phase of the menstrual cycle. The benefit derived from estrogen therapy in the prevention of postpartum breast engorgement must be carefully weighed against the potential increased risk of puerperal thromboembolism associated with the use of large doses of estrogens.


5.2 MeSH Pharmacological Classification

Estrogens, Non-Steroidal

Non-steroidal compounds with estrogenic activity. (See all compounds classified as Estrogens, Non-Steroidal.)


Antineoplastic Agents, Hormonal

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079) (See all compounds classified as Antineoplastic Agents, Hormonal.)


5.3 ATC Code

G - Genito urinary system and sex hormones

G03 - Sex hormones and modulators of the genital system

G03C - Estrogens

G03CA - Natural and semisynthetic estrogens, plain

G03CA06 - Chlorotrianisene


5.4 Absorption, Distribution and Excretion

Absorption

Absorption following oral administration is rapid.


...LONG-ACTING...BECAUSE OF SEQUESTRATION IN ADIPOSE TISSUE &, THEREFORE, IS NOT WIDELY USED.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1431


...SUGGESTS THAT DRUG IS CONVERTED IN LIVER TO MORE ACTIVE FORM. ... IT IS STORED IN FAT, FROM WHICH IT IS SLOWLY RELEASED TO GIVE SUSTAINED ACTION.

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 918


ESTROGENIC ACTIVITY HAS BEEN FOUND IN ADIPOSE TISSUE UP TO MONTH AFTER CESSATION OF THERAPY.

American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 562


5.5 Metabolism/Metabolites

Metabolized principally in the liver, although the kidneys, gonads, and muscle tissues may be involved to some extent. The metabolic fate of the synthetic estrogens has not been fully elucidated.


RATE OF O-DEMETHYLATION WAS MAXIMAL AT 0.4 MMOLAR NADPH. ALTHOUGH NADH DID NOT CATALYZE REACTION ALONE, IT HAD SYNERGISTIC EFFECT IN PRESENCE OF EQUIMOLAR AMT OF NADPH. EXTRACTS FROM INCUBATION MIXT CONTAINED 1 MAJOR (MONO-O-DEMETHYLATED) & A MINOR (BIS-O-DEMETHYLATED) METAB.

RUENITZ PC; DRUG METAB DISPOS 6(6) 631 (1978)


5.6 Mechanism of Action

Chlorotrianisene binds to the estrogen receptor on various estrogen receptor bearing cells. Target cells include cells in the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.


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