US2901478A - Phenothiazine compounds - Google Patents
Phenothiazine compounds Download PDFInfo
- Publication number
- US2901478A US2901478A US639208A US63920857A US2901478A US 2901478 A US2901478 A US 2901478A US 639208 A US639208 A US 639208A US 63920857 A US63920857 A US 63920857A US 2901478 A US2901478 A US 2901478A
- Authority
- US
- United States
- Prior art keywords
- melting point
- piperidyl
- phenothiazine
- compounds
- boiling point
- Prior art date
- 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
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- 125000001484 phenothiazinyl group Chemical class C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 10
- -1 PIPERIDYL Chemical group 0.000 claims description 9
- 229950000688 phenothiazine Drugs 0.000 claims description 5
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- 238000009835 boiling Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 9
- 229940075930 picrate Drugs 0.000 description 7
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- IOIRMOPBZLQITN-UHFFFAOYSA-N 10-(1-ethylpiperidin-3-yl)phenothiazine Chemical compound C1N(CC)CCCC1N1C2=CC=CC=C2SC2=CC=CC=C21 IOIRMOPBZLQITN-UHFFFAOYSA-N 0.000 description 1
- IIJDSJZZKCXQAY-UHFFFAOYSA-N 10-(1-ethylpiperidin-3-yl)phenothiazine;hydrochloride Chemical compound Cl.C1N(CC)CCCC1N1C2=CC=CC=C2SC2=CC=CC=C21 IIJDSJZZKCXQAY-UHFFFAOYSA-N 0.000 description 1
- SHIGCOJUQXBINS-UHFFFAOYSA-N 10-(1-methylpiperidin-4-yl)phenothiazine Chemical compound C1CN(C)CCC1N1C2=CC=CC=C2SC2=CC=CC=C21 SHIGCOJUQXBINS-UHFFFAOYSA-N 0.000 description 1
- SRXWLOLJJPXKDX-UHFFFAOYSA-N 10-[(1-methylpiperidin-2-yl)methyl]phenothiazine Chemical compound CN1CCCCC1CN1C2=CC=CC=C2SC2=CC=CC=C21 SRXWLOLJJPXKDX-UHFFFAOYSA-N 0.000 description 1
- SYFXKKWUEQDOCH-UHFFFAOYSA-N 2-chloro-10-(1-methylpiperidin-3-yl)phenothiazine Chemical compound C1N(C)CCCC1N1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 SYFXKKWUEQDOCH-UHFFFAOYSA-N 0.000 description 1
- NNQMLVRKLTZEOA-UHFFFAOYSA-N 2-chloro-10-(1-methylpiperidin-4-yl)phenothiazine Chemical compound C1CN(C)CCC1N1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 NNQMLVRKLTZEOA-UHFFFAOYSA-N 0.000 description 1
- DLYKFPHPBCTAKD-UHFFFAOYSA-N 2-methoxy-10H-phenothiazine Chemical compound C1=CC=C2NC3=CC(OC)=CC=C3SC2=C1 DLYKFPHPBCTAKD-UHFFFAOYSA-N 0.000 description 1
- KOMRAQHGFHMGRF-UHFFFAOYSA-N 2-methyl-10-(1-propylpiperidin-3-yl)phenothiazine Chemical compound C(CC)N1CC(CCC1)N1C2=CC=CC=C2SC=2C=CC(=CC12)C KOMRAQHGFHMGRF-UHFFFAOYSA-N 0.000 description 1
- LUEVNSVASOZCPK-UHFFFAOYSA-N 3-methoxy-10-(1-methylpiperidin-3-yl)phenothiazine Chemical compound C12=CC=CC=C2SC2=CC(OC)=CC=C2N1C1CCCN(C)C1 LUEVNSVASOZCPK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Definitions
- the compounds of this invention may readily be prepared by reacting a compound having the formula with a compound having the formula A Y-Ofi ⁇ N-R1 ⁇ B/ III wherein R R A and B are as above defined, and Y is halogen.
- the reaction is carried out in the presence of a basic condensing agent such as sodamide, lithium amide, sodium, sodium alcoholate, sodium hydride, and the like, and in the presence of an inert solvent such as benzene, toluene, xylene, cyclohexane, tetralin, decalin, and the like.
- a basic condensing agent such as sodamide, lithium amide, sodium, sodium alcoholate, sodium hydride, and the like
- an inert solvent such as benzene, toluene, xylene, cyclohexane, tetralin, decalin, and the like.
- EXAMPLE 1 10-(1-ethyl-3-piperidyl) phenothiazine hydrochloride A mixture of 0.25 mole of phenothiazine and 0.31 mole of lithium amide in 250 ml. of tetralin is heated at -175 C. for about two hours, then 0.25 mole of lethyl-3-bromopiperidine in- 150 ml. of tetralin is added over a period of two hours at -175" C. After the addition has been completed, heating is continued at 170-175 C. for three to four hours. After cooling, the product is extracted with aqueous acetic acid and the organic layer is removed.
- the aqueous layer is made strongly alkaline with sodium hydroxide and the organic base is extracted with ether.
- the ether is removed, yielding 10-(l-ethyl-3-piperidyl)phenothiazine which distills at 220-225 C./2-3 mm.
- the hydrochloride is prepared by heating the free base in aqueous hydrochloric acid and allowing the resulting liquid to cool, whereupon the desired substance is obtained, M.P. 230-231 C.
- l0-(l-n-butyl-3-piperidyl)phenothiazine Boiling point 235-240 C./2-3 mm.; the hydrochloride is hygroscopic, and the melting point thereof cannot be determined.
- a piperidyl substituted phenothiazine compound selected from the group consisting of compounds of the formula wherein R is lower alkyl and R is selected from the group consisting of hydrogen, halogen, lower alkyl and lower alkoxy, and the non-toxic acid addition salts thereof.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Description
United States Patent PHENOTHIAZINE COR/[POUNDS Wilhelm Alfons Schuler, Bad Hamburg vor der Hohe, Germany, assignor to Chemische Fabrik Promonta, G.m.b.H.
No Drawing. Application February 11, 1957 Serial No. 639,208
6 Claims. (Cl. 260-243) wherein R denotes lower alkyl, R denotes hydrogen, halogen, lower alkyl or lower alkoxy. A denotes methylene or ethylene, B denotes ethylene or propylene, the sum of the number of carbon atoms contained in the radicals A and B being four. Also included in this invention are the nontoxic acid addition salts of the compounds having the above structural formula.
It is an object of this invention to provide compounds which generally depress the vital body functions such as the blood pressure and the pulse and breathing rates. Further, these compounds potentiate the physiological action of narcotics-a property which renders them extremely valuable in surgery.
The compounds of this invention may readily be prepared by reacting a compound having the formula with a compound having the formula A Y-Ofi \N-R1 \B/ III wherein R R A and B are as above defined, and Y is halogen.
The reaction is carried out in the presence of a basic condensing agent such as sodamide, lithium amide, sodium, sodium alcoholate, sodium hydride, and the like, and in the presence of an inert solvent such as benzene, toluene, xylene, cyclohexane, tetralin, decalin, and the like. The free bases obtained by the reaction described above, are converted to nontoxic acid addition salts thereof with inorganic acids or organic acids, in the usual manner.
The following example will serve to illustrate this invention:
EXAMPLE 1 10-(1-ethyl-3-piperidyl) phenothiazine hydrochloride A mixture of 0.25 mole of phenothiazine and 0.31 mole of lithium amide in 250 ml. of tetralin is heated at -175 C. for about two hours, then 0.25 mole of lethyl-3-bromopiperidine in- 150 ml. of tetralin is added over a period of two hours at -175" C. After the addition has been completed, heating is continued at 170-175 C. for three to four hours. After cooling, the product is extracted with aqueous acetic acid and the organic layer is removed. The aqueous layer is made strongly alkaline with sodium hydroxide and the organic base is extracted with ether. The ether is removed, yielding 10-(l-ethyl-3-piperidyl)phenothiazine which distills at 220-225 C./2-3 mm. The hydrochloride is prepared by heating the free base in aqueous hydrochloric acid and allowing the resulting liquid to cool, whereupon the desired substance is obtained, M.P. 230-231 C.
In a corresponding manner, the following compounds were prepared:
10-(1-methyl-4-piperidyl)phenothiazine: Boiling point.
196 C./2-3 mm.; melting point of hydrochloride 244-246 C.
10-( l-methyl-3 -piperidyl) -2-chlorophenothiazine: Boiling point 191/ 0.1 mm.; melting point of hydrochloride 203-206" C.
10( 1-methyl-3 -piperidyl -4-chlorophenothiazine: Boiling point 187-189 C./0.l8 mm.; melting point of picrate 181-183 C. (dec); melting point of hydrochloride 227-230 C. (dec).
10-(1-n-propyl-3-piperidyl)-2-methylphenothiazine: Boiling point -178 C./0.075 mm.; melting point of picrate l69-l71 C.; melting point of oxalate 178- C.
10-( l-n-propyl-3piperidyl) -3-methylphenothiazine: Boiling point 178-179 C./0.10 mm.; melting point of picrate 153-154 C.; melting point of oxalate 164- 166 C.
10( 1-n-propyl-3 -piperidyl) -4-methylphenothiazine: Boiling point 174-175 C./0.l mm.; melting point of picrate 141-143 C. (dec); melting point of oxalate 180-182 C. (dec).
10 (l propyl 3 piperidyl) 2 methoxyphenothiazine: Boiling point 208-210 C./0.4 mm.; melting point of picrate 168-171 C.
10-(l-methyl-3-piperidyl)-3-methoxyphenothiazine: Boiling point -186 C./0.06 mm.; melting point of picrate l94-196 C. (dec).
10-( 1-methyl-4-piperidyl) -2-chlorophenothiazine: Boiling point 198-200 C./2-3 mm.; hydrochloride is bygroscopic, and the melting point thereof could not be determined.
l0( 1-methyl-4-piperidyl) -4-chloropl1enothiazine: Boiling point 194-198 C./ 0.3 mm.; melting point of picrate 180-182" C. (dec); melting point of oxalate 217- 220 C. (dec).
10( 1-methyl-3 -piperidyl phenothiazine:
of hydrochloride 236-238 C.
l0-(l-n-butyl-3-piperidyl)phenothiazine: Boiling point 235-240 C./2-3 mm.; the hydrochloride is hygroscopic, and the melting point thereof cannot be determined.
Melting point Since certain changes may be made in the compounds above described without departing from the scope of this invention, it is intended that all matter contained in the above description shall be interpreted as illustrative, and not in a limiting sense.
I claim:
1. A piperidyl substituted phenothiazine compound selected from the group consisting of compounds of the formula wherein R is lower alkyl and R is selected from the group consisting of hydrogen, halogen, lower alkyl and lower alkoxy, and the non-toxic acid addition salts thereof.
References Cited in the file of this patent UNITED STATES PATENTS Robinson et al. Mar. 25, 1952 Schuler Mar. 5, 1957 OTHER REFERENCES Nieschulz et aL: Arzneimittel Forsch, vol. 4, Apr. 1954, pp. 232, 233, 234 and 241.
Viaud: J. Pharm. Pharmacol, vol. 6 (1954), pp. 361 and 364.
Claims (1)
1. A PIPERIDYL SUBSTITUTED A PHENOTHIAZINE COMPOUND SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS OF THE FORMULA
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US639208A US2901478A (en) | 1957-02-11 | 1957-02-11 | Phenothiazine compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US639208A US2901478A (en) | 1957-02-11 | 1957-02-11 | Phenothiazine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2901478A true US2901478A (en) | 1959-08-25 |
Family
ID=24563166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US639208A Expired - Lifetime US2901478A (en) | 1957-02-11 | 1957-02-11 | Phenothiazine compounds |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2901478A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3239514A (en) * | 1956-04-18 | 1966-03-08 | Sandoz Ltd | Phenothiazine derivatives substituted by a monovalent sulfur function in 3-position |
| WO2002057244A1 (en) * | 2001-01-19 | 2002-07-25 | Cytokinetics, Inc. | Phenothiazine kinesin inhibitors |
| US20030054038A1 (en) * | 2001-06-22 | 2003-03-20 | Crew Marshall D. | Pharmaceutical compositions of drugs and neutralized acidic polymers |
| US20050009860A1 (en) * | 2003-06-27 | 2005-01-13 | Carson John R. | Tricyclic delta-opioid modulators |
| US20060030585A1 (en) * | 2004-08-05 | 2006-02-09 | Scott Dax | Tricyclic delta-opioid modulators |
| US20060135524A1 (en) * | 2004-12-22 | 2006-06-22 | Carson John R | Tricyclic delta-opioid modulators |
| US20060135763A1 (en) * | 2004-12-22 | 2006-06-22 | Coats Steve J | Tricyclic delta-opioid modulators |
| US20060135522A1 (en) * | 2004-12-22 | 2006-06-22 | Carson John R | Tricyclic delta-opioid modulators |
| US20060148823A1 (en) * | 2005-01-06 | 2006-07-06 | Coats Steven J | Tricyclic delta-opioid modulators |
| US20060287297A1 (en) * | 2005-06-16 | 2006-12-21 | Decorte Bart | Tricyclic opioid modulators |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2590125A (en) * | 1952-03-25 | Quaternary-ammonium alkyl | ||
| US2784185A (en) * | 1953-03-27 | 1957-03-05 | Promonta Chem Fab | Phenothiazine compounds |
-
1957
- 1957-02-11 US US639208A patent/US2901478A/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2590125A (en) * | 1952-03-25 | Quaternary-ammonium alkyl | ||
| US2784185A (en) * | 1953-03-27 | 1957-03-05 | Promonta Chem Fab | Phenothiazine compounds |
Cited By (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3239514A (en) * | 1956-04-18 | 1966-03-08 | Sandoz Ltd | Phenothiazine derivatives substituted by a monovalent sulfur function in 3-position |
| WO2002057244A1 (en) * | 2001-01-19 | 2002-07-25 | Cytokinetics, Inc. | Phenothiazine kinesin inhibitors |
| US20040132719A1 (en) * | 2001-01-19 | 2004-07-08 | Finer Jeffrey T | Phenothiazine kinesin inhibitors |
| US20060014736A1 (en) * | 2001-01-19 | 2006-01-19 | Cytokinetics, Inc. | Phenothiazine kinesin inhibitors |
| US6992082B2 (en) | 2001-01-19 | 2006-01-31 | Cytokinetics, Inc. | Phenothiazine kinesin inhibitors |
| US7119089B2 (en) | 2001-01-19 | 2006-10-10 | Cytokinetics, Inc. | Phenothiazine kinesin inhibitors |
| US20060204577A1 (en) * | 2001-06-22 | 2006-09-14 | Crew Marshall D | Pharmaceutical Compositions of Drugs and Neutralized Acidic Polymers |
| US20030054038A1 (en) * | 2001-06-22 | 2003-03-20 | Crew Marshall D. | Pharmaceutical compositions of drugs and neutralized acidic polymers |
| US8147872B2 (en) | 2001-06-22 | 2012-04-03 | Bend Reseach, Inc. | Pharmaceutical compositions of drugs and neutralized acidic polymers |
| US20060003011A1 (en) * | 2001-06-22 | 2006-01-05 | Pfizer Inc | Pharmaceutical compositions of drugs and neutralized acidic polymers |
| US8173142B2 (en) | 2001-06-22 | 2012-05-08 | Bend Research, Inc. | Pharmaceutical compositions of drugs and neutralized acidic polymers |
| US8350041B2 (en) | 2003-06-27 | 2013-01-08 | Janssen Pharmaceutica, Nv | Tricyclic δ-opioid modulators |
| US20050009860A1 (en) * | 2003-06-27 | 2005-01-13 | Carson John R. | Tricyclic delta-opioid modulators |
| US7982042B2 (en) | 2003-06-27 | 2011-07-19 | Janseen Pharmacautica NV | Thiozanthene derivatives as delta-opioid modulators |
| US7589103B2 (en) | 2003-06-27 | 2009-09-15 | Janssen Pharmaceutica N.V. | Tricyclic-bridged piperidinylidene derivatives as 8-opioid modulators |
| US8106207B2 (en) | 2003-06-27 | 2012-01-31 | Janssen Pharmaceutica, Nv | Tricyclic δ-opioid modulators |
| US20090291979A1 (en) * | 2004-08-05 | 2009-11-26 | Scott Dax | Tricyclic-bridged piperidinylidene derivatives as delta opioid modulators |
| US20060030585A1 (en) * | 2004-08-05 | 2006-02-09 | Scott Dax | Tricyclic delta-opioid modulators |
| US7553850B2 (en) | 2004-08-05 | 2009-06-30 | Janssen Pharmaceutica Nv | Tricyclic-bridged piperidinylidene derivatives as δ-opioid modulators |
| US20060135524A1 (en) * | 2004-12-22 | 2006-06-22 | Carson John R | Tricyclic delta-opioid modulators |
| US20080306111A1 (en) * | 2004-12-22 | 2008-12-11 | Carson John R | Tricyclic delta- opioid modulators |
| US7439239B2 (en) | 2004-12-22 | 2008-10-21 | Janssen Pharmaceutica N.V. | Tricyclic δ- opioid modulators |
| US7589104B2 (en) | 2004-12-22 | 2009-09-15 | Janssen Pharmaceutica Nv | Tricyclic-bridged piperidinyline derivatives as §-opioid modulators |
| US20100093709A1 (en) * | 2004-12-22 | 2010-04-15 | Coats Steven J | Tricyclic delta opioid modulators |
| US20060135763A1 (en) * | 2004-12-22 | 2006-06-22 | Coats Steve J | Tricyclic delta-opioid modulators |
| US20060135522A1 (en) * | 2004-12-22 | 2006-06-22 | Carson John R | Tricyclic delta-opioid modulators |
| US7652005B2 (en) | 2004-12-22 | 2010-01-26 | Janssen Pharmaceutica N.V. | Tricyclic δ-opioid modulators |
| US7432257B2 (en) * | 2005-01-06 | 2008-10-07 | Janssen Pharmaceutica N.V. | Piperdinyl-phenoxazine and phenothiazine derivatives as δ-opioid modulators |
| US20080318937A1 (en) * | 2005-01-06 | 2008-12-25 | Coats Steven J | Tricyclic delta-opioid modulators |
| US20060148823A1 (en) * | 2005-01-06 | 2006-07-06 | Coats Steven J | Tricyclic delta-opioid modulators |
| US20090275610A1 (en) * | 2005-06-16 | 2009-11-05 | Decorte Bart | Tricyclic opioid modulators |
| US7582650B2 (en) | 2005-06-16 | 2009-09-01 | Janssen Pharmaceutica N.V. | Tricyclic opioid modulators |
| US20060287297A1 (en) * | 2005-06-16 | 2006-12-21 | Decorte Bart | Tricyclic opioid modulators |
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