US3206501A - (paraacyloxyphenoxy)-benzoic acid derivatives - Google Patents

(paraacyloxyphenoxy)-benzoic acid derivatives Download PDF

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Publication number: US3206501A
Authority: US; United States
Prior art keywords: benzoic acid; diiodo; compounds; iodo; cholesterol level
Prior art date: 1960-11-19
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

US152673A

Other languages

English (en)

Inventor

Masuda Katsutada

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Takeda Pharmaceutical Co Ltd

Original Assignee

Takeda Chemical Industries Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1960-11-19

Filing date

1961-11-15

Publication date

1965-09-14

1961-11-15 Application filed by Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd

1965-09-14 Application granted granted Critical

1965-09-14 Publication of US3206501A publication Critical patent/US3206501A/en

1982-09-14 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

-1 BENZYLCARBONYL Chemical class 0.000 claims description 8
239000005711 Benzoic acid Substances 0.000 claims description 8
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical class C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 28
150000001875 compounds Chemical class 0.000 description 24
239000008280 blood Substances 0.000 description 13
210000004369 blood Anatomy 0.000 description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
125000002252 acyl group Chemical group 0.000 description 8
239000003795 chemical substances by application Substances 0.000 description 8
XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 7
229940034208 thyroxine Drugs 0.000 description 7
XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
239000007858 starting material Substances 0.000 description 6
AXVCIZJRCOHMQX-UHFFFAOYSA-N acetiromate Chemical compound C1=C(I)C(OC(=O)C)=CC=C1OC1=C(I)C=C(C(O)=O)C=C1I AXVCIZJRCOHMQX-UHFFFAOYSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
239000003814 drug Substances 0.000 description 5
229940079593 drug Drugs 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
239000000463 material Substances 0.000 description 4
125000000896 monocarboxylic acid group Chemical group 0.000 description 4
239000002904 solvent Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
UFFBAPYAPOWTEI-UHFFFAOYSA-N 4-(4-hydroxy-3-iodophenoxy)-3,5-diiodobenzoic acid Chemical compound IC1=CC(C(=O)O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 UFFBAPYAPOWTEI-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
206010003210 Arteriosclerosis Diseases 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
208000035150 Hypercholesterolemia Diseases 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000003513 alkali Substances 0.000 description 3
150000001413 amino acids Chemical group 0.000 description 3
208000011775 arteriosclerosis disease Diseases 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000000843 powder Substances 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
235000019441 ethanol Nutrition 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
238000000034 method Methods 0.000 description 2
230000036284 oxygen consumption Effects 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
125000005425 toluyl group Chemical group 0.000 description 2
NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
206010059150 Cerebrosclerosis Diseases 0.000 description 1
208000007530 Essential hypertension Diseases 0.000 description 1
206010020852 Hypertonia Diseases 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
208000034189 Sclerosis Diseases 0.000 description 1
206010039966 Senile dementia Diseases 0.000 description 1
AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000005053 encephalomalacia Diseases 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000011835 investigation Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
230000007721 medicinal effect Effects 0.000 description 1
239000000203 mixture Substances 0.000 description 1
231100000957 no side effect Toxicity 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000012216 screening Methods 0.000 description 1
239000000243 solution Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000005495 thyroid hormone Substances 0.000 description 1
229940036555 thyroid hormone Drugs 0.000 description 1
230000000929 thyromimetic effect Effects 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000002792 vascular Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/62—Halogen-containing esters
- C07C69/63—Halogen-containing esters of saturated acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring

Definitions

the compounds of this invention are O-acyl derivatives of 3,5-diiodo-4-(3'-iodo-4'-hydroxyphenoxy)-benzoic acid.
the most desirable compounds should be one which has a strong effect in lowering blood cholesterol level and does not show any action on the basal metabolism or oxygen consumption.
G. S. Boyd and M. F. Oliver have investigated and compared these properties of variou compounds (Journal of Endocrinology, vol. 2l( 1960- 1961), pp. 25-43) for screening the most desirable compound among them.
3,5-diiodo-4- (4'-hydroxy-3'-iodophenoxy) benzoic acid is acylated.
the non-acylated compound has been reported in such journals as Biochemical Journal, vol. 21 (1927), p. 169, Journal of Biological Chemistry, vol. 179 (1949), p. 423, ibid., vol. 219 (1956), p. 595 and the Journal of the Chemical Society, 1951, p. 2472.
the aforesaid comparative experiment by G. S. Boyd et a1. shows the good results of this compound in lowering blood cholesterol level. In spite of the good results, the compound still has the shortcoming that the lowered blood cholesterol level by this chemical can hardly 'be long-lasting.
the object of this invention is to provide novel compounds which will effect a lower blood cholesterol level and maintain the lowered cholesterol level for a long time. Another object is to provide a method for the production of such compounds. These objects are realized by acylating 3,5-diiodo-4-'(3'iodo-4-hydroxyphenoxy)- benzoic acid.
the acyl group to be substituted for at the 4'-position of the starting material may, for example, be any of lower fatty acid acyl groups such as acetyl, propionyl and butyryl groups, monocyclic aromatic acyl groups such as benzoyl and toluyl groups and aralkyl carboxylic acid acyl groups such as benzyl carbonyl group.
3,5-diiodo-4-(3'-iodo-4'-hydroxyphenoxy)-benzoic acid is acylated.
the acylation may be conducted by action on the starting material of any of conventional acylating agents.
the acylating agent may, for example, be an acid anhydride and acid halide corresponding respectively to the desired acyl group to be introduced.
the action of these acylating agents on the starting material proceeds smoothly under heating with or without use of a suitable solvent.
the solvent if used, may be any inert solvent such as benzene, toluene, ether and petrolic solvent.
a suitable basic material may preferably be used as a deacidating agent.
the basic material any organic or inorganic "basic substances may be employed.
dialkylamine, pyridine, piperidine, alkali hydroxide, alkali carbonate and alkali alcoholate may be used for the purpose.
the former is preferable.
the iodine atom at the 3'-position is sometimes split off under a strong alkalinity.
the product has, in most cases especially where the acyl group is lower fatty acid acyl grou a strong resemblance to the starting material in its behavior, and therefore unreacted material is ditficult to remove if present.
the acylating agent is used in excess so that no unreacted material will remain, and the reaction is conducted until all of the starting material is change to the product.
the end point of the reaction may be observed by utilizing a reagent from the phenolic hydroxyl group such as Paulys reagent, i.e. diazotized sulfanylic acid plus alkali.
a suitable solvent e.g. alcohol and ether gives a highly pure product.
the acute toxicity (LD of 3,5-diiodo-4-(3-iodo-4'- acetyloxyphenoxy)-benzoic acid to mice is 3,000 to 4,000 milligrams per kilogram (per os) or 2,400 milligrams per kilogram (intrapertoneal injecttion).
Other compounds of the present invention also show similar toxicities as the above. Thus, the compounds may safely be administered to living bodies either orally or by injection.
the compounds of this invention are useful for the treatment of various diseases caused from high cholesterol level such as atherosclerosis (cerebrosclerosis, cerebral vascular accident, encephalomalacia, senile dementia, arteriosclerotic parapathy, coronary arteriosclerosis, sclerosis of the aorta, hypertonia) and hypercholesteremia (essential hypercholesteremia)
the compounds may generally be administered orally, but may be administered by injection if desired.
the compounds may be in the form of tablets, granules, powder, internal solution, for instance. formulated with a suitable carrier or suitable carriers.
the administration of the drug may be to 100 milligrams per day per patient as 3,5-diiodo-4- (3'-iodo-4'-acetyloxyphenoxy) benzoic acid.
3,5-diiodo-4- (3'-iodo-4'-acetyloxyphenoxy) benzoic acid 3,5-diiodo-4- (3'-iodo-4'-acetyloxyphenoxy) benzoic acid.
the acyl group at the 4-position is other than acetyl group, the dose, of course, varies with their molecular weights.
the blood cholesterol level of a patient is lowered to a normal level, within 1 to 2 weeks after the start of administration. But, the cholesterol level can not be lowered below the normal level even when the administration is continued.
the total blood cholesterol level of 260 milligrams per deciliter found in a patient of arteriosclerosis (43 years old, female) was lowered to 180 milligrams per deciliter by the administration of 3,5-diiodo-4-(3-iodo-4'-acetyl oxyphenoxy)-benzoic acid (60 milligrams per day) for 100 days.
Another patient (29 years old, female) sufiering from metabolic insufiiciency was given 90 milligrams per day of the same drug as above for days, so that the total blood cholesterol level of 260 milligrams per deciliter was lowered to 154 milligrams per deciliter.
a patient (56 years old, male) with essential hypertension was given 25 to 70 milligrams per day of the same drug as above for 80 days, the total blood cholesterol level of 270 milligrams per deciliter was lowered to 190 milligrams per deciliter.
the administration of the compunds of this invention gives a parallel influence to blood phospholipids with total blood cholesterol level. Just after the start of administration of the drug, the basal metabolic ratio of the patient is slightly heightened, but the heightened ratio slowly drops until a normal ratio is reached. This shows the weak thyromimetic activity of the compounds of this invention.
Example 1 A mixture of 3 parts by Weight of 3,5-diiodo-4-(3'-iodo- 4'-hydroxyphenoxy)-benzoic acid and 10 parts by weight of acetic anhydride is refluxed on an oil bath for a few hours until the reaction to a member from the phenolic hydroxyl group is negative. Then the excess acetic anhydride is removed completely under reduced pressure. After cooling, ether is added to the residue to give a White amorphous powder. Recrystallization of .the powder from glacial acetic acid gives 2.4 parts by weight of 3,5-diiodo- 4-(3'-iodo 4' acetyloxyphenoxy)-benzoic acid as small needles. M.P. 238 C.
the product is slightly soluble in water, glacial acetic acid and ethyl alcohol, and easily soluble in acetone.
Example 2 A process similar to that of Example 1 is conducted employing either normal butyric anhydride or benzoic anhydride instead of acetic anhydride, whereby 3,5-diiodo- 4-(3-iodo-4' normal butyryloxyphenoxy)-benzoic acid (M.P. 225 C.) and 3,5-diiodo-4-(3'-iodo-4-benzoyloxyphenoxy)-benzoic acid (M.P. 148 C.) are obtained respectively.
the analytical values of the products are in accord with the corresponding calculated values.
O-acylv derivatives of 3.5-diiodo 4-(3-iodo-4-hydroxyphenoxy)-benzoic acid wherein the acyl group is a member selected from the group consisting of lower alkanoyl having up to 4 carbon atoms, benzoyl, toluyl, and benzylcarbonyl.

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

US152673A 1960-11-19 1961-11-15 (paraacyloxyphenoxy)-benzoic acid derivatives Expired - Lifetime US3206501A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP4632260		1960-11-19

Publications (1)

Publication Number	Publication Date
US3206501A true US3206501A (en)	1965-09-14

Family

ID=12743912

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
US152673A Expired - Lifetime US3206501A (en)	1960-11-19	1961-11-15	(paraacyloxyphenoxy)-benzoic acid derivatives

Country Status (4)

Country	Link
US (1)	US3206501A (fr)
DE (1)	DE1174327B (fr)
FR (1)	FR1610M (fr)
GB (1)	GB949523A (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3507906A (en) *	1964-08-17	1970-04-21	Allied Chem	Polyesters,intermediates therefor,and processes relating thereto
US3679800A (en) *	1968-04-03	1972-07-25	Ciba Geigy Corp	Bicycloalkyl phenoxyaliphatic acid-compositions
CN108138408A (zh) *	2015-10-01	2018-06-08	朗盛德国有限责任公司	用于生产纤维基质半成品的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2752388A (en) *	1952-08-28	1956-06-26	Strong Cobb And Company Inc	Catalytic mono-acylation of hexylresorcinol and its keto-analog
US2913484A (en) *	1958-05-19	1959-11-17	Dow Chemical Co	Diphenylmethyl 3, 4-dichlorobenzoate
US2970165A (en) *	1957-10-01	1961-01-31	Warner Lambert Pharmaceutical	Sulfate compounds
US2978381A (en) *	1958-06-20	1961-04-04	Freedman Louis	Process and composition for lowering blood serum cholesterol and chylomicron levels
US2980585A (en) *	1958-09-11	1961-04-18	Stambul Rae	Controlling the blood cholesterol level by administration of diiodotyrosine polypeptide

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1078582B (de) *	1958-10-29	1960-03-31	Hoechst Ag	Verfahren zur Herstellung substituierter Thyropropionsaeuren

1961
- 1961-11-15 US US152673A patent/US3206501A/en not_active Expired - Lifetime
- 1961-11-17 DE DET21132A patent/DE1174327B/de active Pending
- 1961-11-17 FR FR879366A patent/FR1610M/fr active Active
- 1961-11-20 GB GB41429/61A patent/GB949523A/en not_active Expired

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2752388A (en) *	1952-08-28	1956-06-26	Strong Cobb And Company Inc	Catalytic mono-acylation of hexylresorcinol and its keto-analog
US2970165A (en) *	1957-10-01	1961-01-31	Warner Lambert Pharmaceutical	Sulfate compounds
US2913484A (en) *	1958-05-19	1959-11-17	Dow Chemical Co	Diphenylmethyl 3, 4-dichlorobenzoate
US2978381A (en) *	1958-06-20	1961-04-04	Freedman Louis	Process and composition for lowering blood serum cholesterol and chylomicron levels
US2980585A (en) *	1958-09-11	1961-04-18	Stambul Rae	Controlling the blood cholesterol level by administration of diiodotyrosine polypeptide

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3507906A (en) *	1964-08-17	1970-04-21	Allied Chem	Polyesters,intermediates therefor,and processes relating thereto
US3679800A (en) *	1968-04-03	1972-07-25	Ciba Geigy Corp	Bicycloalkyl phenoxyaliphatic acid-compositions
CN108138408A (zh) *	2015-10-01	2018-06-08	朗盛德国有限责任公司	用于生产纤维基质半成品的方法
CN108138408B (zh) *	2015-10-01	2020-09-04	朗盛德国有限责任公司	用于生产纤维基质半成品的方法

Also Published As

Publication number	Publication date
DE1174327B (de)	1964-07-23
FR1610M (fr)	1962-12-10
GB949523A (en)	1964-02-12

Publication	Publication Date	Title
DE3219244A1 (de)	1982-12-09	Sulfonatderivate, verfahren zu ihrer herstellung und diese derivate enthaltende arzneimittel
Fried et al.	1950	The hypotensive principles of Veratrum viride
US3636120A (en)	1972-01-18	Prostaglandin e primary alcohols
US3206501A (en)	1965-09-14	(paraacyloxyphenoxy)-benzoic acid derivatives
HU191531B (en)	1987-03-30	Process for the production of /halogen-phenyl/-glyceride esters
JPH0131484B2 (fr)	1989-06-26
US4439366A (en)	1984-03-27	Derivatives of chenodeoxycholic acid
HU192944B (en)	1987-08-28	Process for preparing quinone derivatives
DE2837414C2 (fr)	1987-09-03
CA1040213A (fr)	1978-10-10	Derives de l'acide cycloalkyl phenoxycarboxylique
US4709076A (en)	1987-11-24	Methods, compositions and compounds for the treatment of prostatic adenoma
JPS6246554B2 (fr)	1987-10-02
CA2487165C (fr)	2010-09-21	Dimeres d'acide cinamique, preparation associee et utilisation correspondante dans le traitement des maladies neurodegeneratives
DE1668896C3 (de)	1974-08-29	Phenoxyalkancarbonsäuren ihre Salze und Ester und Verfahren zur Herstellung dieser Verbindungen
US3646122A (en)	1972-02-29	Decahydronaphthyl substituted phenoxyaliphatic acids
US4275068A (en)	1981-06-23	Lipid lowering alkylene glycols and ester derivatives thereof
CH643843A5 (de)	1984-06-29	Phenthiazin-derivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische praeparate.
US3776944A (en)	1973-12-04	Tetraloneoxy acetic acids and esters thereof
FOX	1947	Acyclic enediols. A new method of preparation
US3511871A (en)	1970-05-12	Glycyrrhetinic acid derivatives
US4841097A (en)	1989-06-20	Dialkanoyloxybenzylidene dialkanoate
KR840001838B1 (ko)	1984-10-22	옥시아세트산 유도체의 제조방법
EP0040433B1 (fr)	1984-11-07	Dérivés de l'acide nicotinique de la glucosamine, méthodes pour leur préparation et compositions pharmaceutiques les contenant
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