- 2,1,3-Benzothiadiazine derivatives: Synthesis and screening versus PDE4 enzyme
-
A series of N-1,3 disubstituted 2,1,3-benzothiadiazine derivatives (BTDs) were synthesized and evaluated for their inhibitory activity versus enzymatic isoform PDE4 extracted from U937 cell line. Some of the tested compounds showed a high PDE4 inhibitory activity at 100:μM and the IC50 value of the most interesting terms were evaluated. The structure-activity relationships of these compounds showed that the 3,5-di-tert-butyl-4-hydroxybenzyl moiety at N-1 position is important to obtain activity at micromolar level as previously reported. For the same compounds the antioxidant activity were evaluated highlighting 14 as the most significative one. The introduction of other bulky substituents in N-1 position is detrimental.
- Tait, Annalisa,Luppi, Amedeo,Avallone, Rossella,Baraldi, Mario
-
p. 653 - 663
(2007/10/03)
-
- Piperidyindoles as serotonin receptor ligands
-
A pharmaceutical compound of the formula (I) in which R1 and R2 are each hydrogen or C1-6 alkyl, R3 is —SR10, —SOR10, —SO2R10, —COR10, —CH2OH or —CONHR11, where R10 is C1-6 alkyl and R11 is hydrogen or C1-6 alkyl, R4, R5, R6 and R7 are each hydrogen or C1-6 alkyl, provided that at least one of R4, R5, R6 and R7 is C1-6 alkyl, R8 and R9 are each hydrogen, halo, C1-6 alkyl or cyano, n is 0 or 1 and m is 2 or 3, x is a (a) or (b), and y is (c) or (d), wherein R12 and R13 are each hydrogen, C1- alkyl, cyclopropyl or cyclopropyl-C1-6 alkyl; and salts thereof.
- -
-
-
- 3-Azabicyclo[3.1.0]hexane derivatives useful in therapy
-
Compounds of formula (I), their salts and prodrugs thereof, where the substituents are as defined herein are disclosed as opiate binding agents useful in the treatment of opiate-mediated conditions. Also described are processes for making such substances.
- -
-
-
- Orally active isoxazoline glycoprotein IIb/IIIa antagonists with extended duration of action
-
Modification of the α-carbamate substituent of isoxazoline GPIIb/IIIa (α(IIb)β3) antagonist DMP 754 (7) led to a series of α-sulfonamide and α-sulfamide diaminopropionate isoxazolinylacetamides which were found to be potent inhibitors of in vitro platelet aggregation. Aryl- and heteroaryl-α- sulfonamide groups, in conjunction with (5R)-isoxazoline (2S)- diaminopropionate stereochemistry, were found to impact a pronounced duration of antiplatelet effect in dogs, potentially due to high affinity for unactivated platelets. Isoxazolylsulfonamide 34b (DMP 802), a highly selective GPIIb/IIIa antagonist, demonstrated a prolonged duration of action after iv and po dosing and high affinity for resting and activated platelets. The prolonged antiplatelet profile of DMP 802 in dogs and the high affinity of DMP 802 for human platelets may be predictive of clinical utility as a once-daily antiplatelet agent.
- Olson, Richard E.,Sielecki, Thais M.,Wityak, John,Pinto, Donald J.,Batt, Douglas G.,Frietze, William E.,Liu, Jie,Tobin, A. Ewa,Orwat, Michael J.,Di Meo, Susan V.,Houghton, Gregory C.,Lalka, George K.,Mousa, Shaker A.,Racanelli, Adrienne L.,Hausner, Elizabeth A.,Kapil, Ram P.,Rabel, Shelley R.,Thoolen, Martin J.,Reilly, Thomas M.,Anderson, Paul S.,Wexler, Ruth R.
-
p. 1178 - 1192
(2007/10/03)
-
- Sulfamates as antiglaucoma agents
-
Sulfamate esters of the formula where A is aryloxyalkyl, p is the number of unreacted hydroxy groups present on the alkyl moiety and may be zero, z is the number of --OS(O)2 NR1 R2 groups attached to carbons of the alkyl moiety and is always at least one; R1 and R2 are selected from hydrogen, loweralkyl, carboxy, and the like are useful in treating glaucoma.
- -
-
-
- Compounds having one or more aminosulfaonyloxy radicals useful as pharmaceuticals
-
Methods of treating chronic arthritis and osteoporosis which utilize both known and novel compounds which would fall under the general formula:(HO)p--A--[--OS(O) 2 NR 1 R 2 ] zwherein A encompasses a wide range of values including but not limited to aryl, loweralkyl, cycloalkyl, and carbohydrates including sucrose and fructose; p is equal to the number of unreacted hydroxy groups contained on the molecule and may be zero; z is the number of --OS(O) 2 NR 1 R 2 groups and is always at least one; R 1 and R 2 are selected from hydrogen, loweralkyl, carboxy and the like; a novel process for preparing the compounds is provided wherein an appropriate sulfamic acid aryl ester is reacted with a hydroxy substituted A radical which may or may not contain thereon protected carboxyl, amino or hydroxy substituents, in an aprotic solvent containing a tertiary amine base. Pharmaceutical compositions for the treatment of chronic arthritis and osteoporosis are also provided.
- -
-
-
- Process for the preparation of 3-isopropyl-benzo-2-thia-1,3-diazinone-(4)-2,2-dioxide
-
The present invention relates to a process for the preparation of 3-isopropyl-benzo-2-thia-1,3-diazinone-(4)-2,2-dioxide which comprises preparing isopropyl sulfamoyl chloride in one step by reacting N,N'-diisopropyl-urea with phosphorus trichloride and chlorine in the presence of oleum and sulfuric acid and condensing the so obtained isopropyl sulfamoyl chloride at room temperature without any solvent in the presence of an excess of N,N-diethyl aniline with anthranylic acid methyl ester and subjecting the thus obtained N-isopropyl-N'-o-carbomethoxy-phenyl-sulfamide to cyclization in the presence of sodium methylate, extracting the obtained crude 3-isopropyl-benzo-2-thia-1,3-diazinone-(4)-2,2-dioxide with a mixture of methanol and water and after adding water to the aqueous-methanolic mixture and sedimenting the contaminations isolating a product of high purity.
- -
-
-
- Preparation of sulfamyl halides
-
Sulfamyl halides are prepared by reacting sulfamic acids with halogen in the presence of phosphorus or of a phosphorus trihalide; the sulfamic acid can first be prepared from an isocyanate or urea and then be reacted as above in a one-vessel method. The compounds obtainable by the process of the invention are valuable starting materials for the preparation of crop protection agents, dyes and drugs.
- -
-
-
- Manufacture of sulfamic acid halides
-
Sulfamic acid halides are produced by reaction of sulfamic acids with phosphorus pentahalide in the presence of phosphorus oxyhalide in specific molar ratios and in the presence of halohydrocarbons. The products, some of which are new compounds, are starting materials for the manufacture of plant protection agents, dyes and pharmaceuticals.
- -
-
-
- N-pyrazinecarbonyl-N'-substituted-sulfamoylguanidine and processes for preparing same
-
The case involves novel N-pyrazinecarbonyl-N'-substituted-sulfamoylguanidine and processes for preparing same. The N-pyrazinecarbonyl-N'-substituted-sulfamoylguanidines are excellent eukalemic agents possessing diuretic and natriuretic properties.
- -
-
-
- Production of sulfamic acid halides
-
The production of sulfamic acid halides by reaction of sulfamic acids with acid halides, and the new sulfamic acid halides. The products are starting materials for the production of plant protection agents, dyes and pharmaceuticals.
- -
-
-
