公开(公告)号：BR6683346D0

公开(公告)日：1973-12-26

申请号：BR18334666

申请日：1966-09-30

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: A61K38/00 ,  C08G69/08 ,  C12N11/08

Abstract: A process for the preparation of water soluble proteins and peptides of high molecular weight, by coupling amino, carboxyl or hydroxyl- containing polaminocarboxylicacids with proteins or peptides. In this way strongly cross-linked products are obtained since the polyaminocarboxylic acids contain several functional groups. The products are suitable for use as antigens in immuno-therapy, or can be used for the determination of insulin and gonadotropin. The preparation of cross-linked proteins with a molecular weight of up to 250,000, which are soluble in water, formed by coupling polyaminocarboxylic acids with suitable proteins.

公开(公告)号：BR6682693D0

公开(公告)日：1973-12-26

申请号：BR18269366

申请日：1966-09-08

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: A61K31/64 ,  C07C67/00 ,  C07C301/00 ,  C07C303/36 ,  C07C303/40 ,  C07C311/54 ,  C07C311/59 ,  C07D333/06 ,  C07D333/32

Abstract: Benzenesulfonylureas of general formula (I): X - CO - - Y - phenylene - SO2 - NH - CO-NH-R' R = H, low alkyl or low phenylalkyl; R' = nortricyclyl or adamantyl; X = a) a phenylgroup carrying at random positions the substituents Z and Z' which may be equal or different. Z = H, halogen, low alkyl, alkenyl, alkoxy, alkenoxy, halogenalkoxy, alkoxyalkoxy, phenalkoxy, phenylalkyl, cycloalkoxy, phenyl, phenoxy, low acyl, benzoyl, trifluoromethyl, hydroxy, low acyloxy, -CN or -NO2; Z' = H, halogen, Low alkyl, alkoxy, alkoxyalkoxy, halogenalkoxy or acyloxy, hydroxy; b) a naphthylgroup possibly mono- or disubstituted with halogen, low alkyl, low alkoxy or hydroxyl; c) a tetrahydronaphthyl- or indanylgroup; d) a thiophenylgroup possibly mono- or disubstituted with low alkyl, phenylalkyl, alkoxy, alkoxyalkoxy, alkenoxy, phenylalkoxy or halogenalkoxy, aryl or halogen; e) a tetramethylene- or trimethylenetenylgroup; Y = a hydrocarbon group with 1-4C-atoms The phenylenegroup in the formula is preferably not substituted, but may be substituted once or more times with low alkyl, halogen, or low alkoxy; the group can connect the other parts of the molecule in ortho-,meta- or preferably para position. The new compounds have a very strong blood sugar lowering activity with very good tolerance and may be used in the treatment of diabetus mellitus.

公开(公告)号：BR6681324D0

公开(公告)日：1973-12-26

申请号：BR18132466

申请日：1966-07-15

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: A61K31/505 ,  C07D239/92

公开(公告)号：BR6680469D0

公开(公告)日：1973-12-26

申请号：BR18046966

申请日：1966-06-16

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: C07D335/02

Abstract: Novel compounds of the formula (wherein R is H, lower alkyl or phenyl lower alkyl; R1 is C2- 8 alkyl, C2- 8 alkenyl, C2- 8 mercaptoalkyl, C4- 8 alkoxyalkyl, C4- 8 alkylmercaptoalkyl, C4- 8 alkylsulphinylalkyl, phenyl lower alkyl, phenylcyclopropyl, cyclohexyl lower alkyl, cycloheptylmethyl, cycloheptyl ethyl, cyclo-octylmethyl, C7- 9 endoalkylenecyclohexyl, C7- 9 endoalkylenecyclohexenyl, C8- 10 endoalkylenecyclohexylmethyl, C8- 10\t endoalkylenecyclohexenylmethyl, lower alkyl cyclohexyl, lower alkoxy cyclohexyl, C5- 8 cycloalkyl, cyclohexenyl, cyclohexenylmethyl, or a C4 or C5 heterocyclic ring containing one O or S atom and up to 2 double bonds and linked directly or via a methylene group to the N atom; X is H, halogen, lower alkyl, lower alkoxy CF3 or NO2; Y is a C1- 4 hydrocarbon chain n is 1, 2 or 3; U is O or S; and Z is an aliphatic or cycloaliphatic hydrocarbon of at most 6 carbon atoms, a phenyl or a benzyl radical; the word "lower" referring to groups containing at most 4 carbon atoms) and salts thereof are prepared (1) by reaction of an appropriate amine R1NH2 or a salt thereof with an appropriately substituted benzenesulphonyl-isocyanate, -carbamic acid ester, -thiocarbamic acid ester, -carbamic acid halide, or -urea; (2) by reaction of an R1-substituted isocyanate, carbamic or thiocarbamic acid ester, carbamic acid halide or urea with the appropriately substituted benzene sulphonamide; (3) by reaction of an R1-substituted urea, isourea or isothiourea ether or parabanic acid with the appropriately substituted benzenesulphonyl halide and hydrolysis of the product; (4) by exchange of the S atom in a correspondingly substituted benzenesulphonyl thiourea for an O atom; (5) by oxidation of a corresponding benzenesulphinyl-urea or benzene sulphenylurea; or (6) by acylation of appropriate RHN-Y-C6H5-SO2NHCONHR1 compound. These methods and variants thereof are described and exemplified. The benzenesulphonyl ureas of the invention, which are stated to have a blood sugar lowering, i.e. hypoglycemic, action, may be incorporated in pharmaceutical compositions for oral administration.

公开(公告)号：BR6680181D0

公开(公告)日：1973-12-26

申请号：BR18018166

申请日：1966-06-03

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: C07C217/62 ,  C07D213/38

Abstract: Compounds of the general Formula (I) (wherein R1 represents a phenyl, methoxyphenyl or 2-pyridyl group, R2 represents a hydrogen atom or a methyl group and R3 and R4 each represent a C1- 4 alkyl group) and their acid addition salts are prepared by standard methods, e.g. reducing a compound of the Formula (II) (wherein R represents a hydrogen atom) or a salt thereof, or condensing a compound of the Formula (III) with a compound of the Formula (IV) (wherein X represents and reducing the product, optionally followed in either case by salt formation. The preparation of starting materials of Formulae (II) and (IV) is described. The compounds of the invention are useful in the treatment of hypertonia, and may be administered in the form of pharmaceutical preparations containing them in association with a carrier.

公开(公告)号：BR7208928D0

公开(公告)日：1973-12-11

申请号：BR892872

申请日：1972-12-19

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: C08G69/26 ,  C08G20/20

公开(公告)号：BR6685071D0

公开(公告)日：1973-12-04

申请号：BR18507166

申请日：1966-12-02

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: A61K31/64 ,  C07D309/14

Abstract: 1,171,935. Benzenesulphonyl ureas. FARBWERKE HOECHST A.G. 1 Dec., 1966 [2 Dec., 1965], No. 53773/66. Heading C2C. The invention comprises compounds of formula wherein R is H, C 1-4 alkyl or phenyl-C 1-4 . alkyl; R 1 is a C 2-8 alkyl, alkenyl or mercaptoalkyl group, a C 4-8 alkoxyalkyl, alkylmercaptoalkyl or alkylsulphinylalkyl group containing at least 2 carbon atoms in the alkylene part, phenyl - C 1-4 - alkyl, phenylcyclopropyl, cyclohexyl - C 1-4 - alkyl, cycloheptylmethyl, cycloheptylethyl, cyclooctylmethyl, an endoalkylenecyclohexyl, -cyclohexenyl, -cyclohexylmethyl or cyclohexenylmethyl group containing 1 or 2 carbon atoms in the endoalkylene part, (C 1-4 alkyl)-cyclohexyl, (C 1-4 alkoxy)-cyclohexyl, C 5-8 cycloalkyl, cyclohexenyl, cyclohexenylmethyl, or a C 4-5 O or C 4-5 S heterocyclic ring optionally containing 1 or 2 ethylenic double bonds and connected to the nitrogen atom either directly or via a CH 2 group: Y is a C 1-4 hydrocarbon chain; Z is C 5-6 aliphatic hydrocarbyl, or a phenyl group optionally substituted by a member selected from C 1-4 alkyl, C 1-4 alkoxy, CF 3 , Cl, Br and F; X is H (provided that Z is optionally substituted phenyl), halogen, C 1-4 alkyl, C 1-4 alkoxy, CF 3 or NO 2 ; and wherein the "phenylene " group is optionally substituted by one or more members selected from C 1-4 alkyl, C 1-4 alkoxy and halogen; and the physiologically tolerable salts of such compounds. These compounds are prepared by (a) reacting R 1 NH 2 or a salt thereof with an appropriately substituted benzenesulphonyl-carbamic acid ester, - thiolcarbamic acid ester, -isocyanate, -urea, - semicarbazide, or -semicarbazone; or (b) reacting an R 1 -substituted isocyanate, carbamic acid ester, thiolcarbamic acid ester, carbamic acid halide or urea with an appropriately substituted benzenesulphonamide; or (c) hydrolysing a correspondingly substituted benzenesulphonyl-isourea ether, -isourea ester, -isothiourea ether, -parabanic acid or -haloformic acid amidine; or (d) hydration of a correspondingly substituted benzenesulphonyl-carbodiimide; or (e) replacing S by O in a correspondingly substituted benzenesulphonyl-thiourea; or (f) by acylating a compound of formula RNH.Y.phenylene.SO 2 .NH.CO.NH.R 1 . Variations of the above methods are also referred to. 4 - [#, - (2 - Phenoxy - benzamido) - ethyl]- benzene-sulphonamide is prepared by reacting 2- phenoxy-benzoyl chloride with 4-(#-aminoethyl)-benzenesulphonamide. N - {4 - [# - (2 - Phenoxy - benzamido) - ethyl]- benzenesulphonyl } - N 1 - cyclohexyl - thiourea is prepared by reacting 4-[#-(2-phenoxy-benzamido) - ethyl] - benzenesulphonamide with cyclohexyl isothiocyanate, and is convertible with mercuric oxide, methanol and K 2 CO 3 into the corresponding isourea methyl ether. N - {4 - [# - (2 - phenoxy - benzamido) - ethyl]- benzenesulphonyl} - urea is prepared by reacting 4 - [# - (2 - phenoxy - benzamido) - ethyl]- benzenesulphonamide with potassium cyanate. N - {4 - [γ - (2 - chloro - 5 - nitro - benzamido)- propyl] - benzenesulphonyl} - N 1 - cyclohexylurea is prepared by reacting 2-chloro-5-nitrobenzoyl chloride with N-[4-(γ-amino-propyl)- benzenesulphonyl} - N 1 - cyclohexyl - urea, the last-named compound being in turn prepared by hydrolysis of the corresponding γ-acetamidopropyl compound. N - {4 - [# - (2 - phenoxy - benzamido)- ethyl] - benzenesulphonyl} - N 1 - (2,5 - endomethylene - cyclohexyl - methyl) - thiourea is prepared by reacting 4 - [# - (2 - phenoxybenzamido) - ethyl] - benzenesulphonamide with 2,5 - endomethylene - cyclohexyl - methyl isothiocyanate. N - {4 - [# - (2 - phenoxy - benzamido) - ethyl]- benzenesulphonyl} - N 1 - cyclohexyl - isothiourea methyl ether is prepared from the corresponding thiourea by reaction with methyl iodide. The benzenesulphonyl-ureas of the invention and their physiologically tolerable salts are stated to possess hypoglemic action and may be made up with carriers into pharmaceutical compositions suitable for oral administration. The salts may be alkali metal or alkaline earth metal salts.

公开(公告)号：BR6678492D0

公开(公告)日：1973-09-18

申请号：BR17849266

申请日：1966-04-05

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: A61K31/38 ,  C07D333/38

Abstract: 1,133,850. Aminothiophene derivatives. FARBWERKE HOECHST A.G. 12 April, 1966 [10 April, 1965], No. 15940/66. Heading C2C. Novel aminothiophene derivatives have the formula where R is a phenyl radical containing one or more substituents which may be a halogen atom, CF 3 , C 1-4 alkyl or C 1-4 alkoxy, phenyl-C 1-4 alkoxy which may be substituted in the phenyl ring by halo, C 1-4 alkyl or C 1-4 alkoxy, and C 5-6 cycloalkyl, or R may represent a tetrahydronaphthalene or indane radical; R 1 is a carboxylic, carbonamide, or carboxylic ester group containing in the ester group (a) an alkyl, dialkyl - amino - alkyl, or alkylene - iminoalkyl radical having 4-5 ring carbons which may be interrupted by O or where each alkyl is C 1-4 ; or (b) a phenyl radical which may be substituted by halo, C 1-4 alkyl or C 1-4 alkoxy; or (c) a phenyl-C 1-4 alkyl radical; and R 2 and R 3 each represents H or C 1-4 alkyl. The novel compounds may be obtained: (1) by condensing a compound of formula where R 4 = R 1 or CN, with R-NH 2 to yield a 3 - amino - 2,5 - dihydrothiophene which is dehydrogenated by known methods and if R 4 = CN it is converted to R 1 ; (2) by condensing a compound of formula with RY, where one of X or Y is amino and the other a halogen atom, and if necessary dehydrogenating and converting R 4 to R 1 ; (3) by de-acylating a compound corresponding to (I) (which may be partially or completely hydrogenated) having an acyl group in place of the H attached to the N atom, and optionally dehydrogenating the product and converting R 4 to R 1 . 4-Cyano-thiophanone is obtained introducing a mixture of acrylonitrile and thioglycolic acid methyl ester into fresh sodium methylate. and refluxing. 3 - (R - substituted - anilino) - 4 - cyano - 2,5- dihydrothiophenea are obtained by reacting 4- cyanothiophane with an R-substituted aniline. 3 - (R - substituted - anilino) - 4 - cyano - thiophenes are obtained by dehydrogenation of the corresponding 2,5-dihydrothiophenes by boiling with tetrachloroquinone. Pharmaceutical compositions having antiphlogistic and anti-pyretic properties comprise compounds of Formula I together with a pharmaceutically suitable carrier in forms such as tablets, dragees, solutions, suppositories, ointments and powders.

公开(公告)号：BR6571355D0

公开(公告)日：1973-09-06

申请号：BR17135565

申请日：1965-07-16

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: A61K31/17 ,  A61K31/64 ,  A61P3/08 ,  C07C67/00 ,  C07C301/00 ,  C07C303/36 ,  C07C303/40 ,  C07C311/54 ,  C07C311/58 ,  C07D335/02

公开(公告)号：BR6456764D0

公开(公告)日：1973-08-14

申请号：BR15676464

申请日：1964-02-07

Applicant: HOECHST AG

Inventor： HOECHST AG

IPC: C07C311/59