cas 16133-25-8, PYRIDINE-3-SULFONYL CHLORIDE HYDROCHLORIDE

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Regioselective Lithiation of 3-Pyridylsulfonic Acid Derivatives: A Convenient Route to Various New 4-Substituted 3-Pyridylsulfonamides
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Breant, P.,Marsais, F.,Queguiner, G.
p. 822 - 824
(1983)
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Synthesis and biological evaluation of N-(7-indolyl)-3-pyridinesulfonamide derivatives as potent antitumor agents.
We herein report the synthesis and antitumor activity of E7070 analogues containing a 3-pyridinesulfonamide moiety. E7070 was selected from our sulfonamide-based compound collections, currently undergoing Phase II clinical trials because of its tolerable toxicity profile and some antitumor responses in the Phase I setting. Of the analogues examined, ER-35745, a 6-amino-3-pyridinesulfonamide derivative, demonstrated significant oral efficacy against the HCT116 human colon carcinoma xenograft in nude mice.
Owa, Takashi,Yoshino, Hiroshi,Okauchi, Tatsuo,Okabe, Tadashi,Ozawa, Yoichi,Hata Sugi, Naoko,Yoshimatsu, Kentaro,Nagasu, Takeshi,Koyanagi, Nozomu,Kitoh, Kyosuke
p. 2097 - 2100
(2002)
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Synthetic method of pyridine-3-sulfonyl chloride
The invention provides a synthetic method for synthesizing pyridine-3-sulfonyl chloride. The synthesis of pyridine-3-sulfonyl chloride comprises the following steps: taking 3-amino pyridine as an initial raw material, separating out an intermediate fluoboric acid diazonium salt, and then carrying out sulfonyl chlorination reaction. The method is low in cost, high in product content, convenient to operate, few in three wastes and suitable for industrial large-scale production.
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Paragraph 0028-0032

(2021/05/26)

SUBSTITUTED QUINOLINES AND METHODS FOR TREATING CANCER
Substituted quinoline compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or ameliorate cancer are provided.
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Paragraph 0310

(2018/05/24)

Environment-friendly chemical synthetic method for 3-pyridine sulfonyl chloride
The invention provides an environment-friendly chemical synthetic method for 3-pyridine sulfonyl chloride. The method comprises the steps of carrying out diazo-reaction, substitution reaction, extraction and distillation on 3-aminopyridine as a starting material, so as to obtain 3-pyridine sulfonyl chloride. By virtue of the method, acylation reagents such as pentachloride phosphorus oxychloride is not used, and reaction conditions are mild, so that the method for producing 3-pyridine sulfonyl chloride belongs to green chemistry, meanwhile, the reaction time is greatly shortened, the yield of the product is increased to be above 80%, and the production cost is greatly lowered.
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Paragraph 0052; 0054-0083

(2017/04/03)

Production of -3 - pyridine sulfonyl chloride
[Problem] to various kinds of synthetic materials or as intermediates for the synthesis of pyridine sulfonyl chloride hydrochloride can be obtained in high purity -3 - useful, easily industrially applicable to the production of -3 - pyridine sulfonyl chloride process. [Solution] pyridine sulfonyl chloride hydrochloride salt in a nonaqueous solvent was prepared by dispersing -3 - dispersion, the dispersion is prepared, for example, atmospheric pressure or under pressure conditions, 75 c 130 °C heating process for preparation of sulfonyl chloride in pyridine sulfonyl chloride with pyridine -3 - -3 -. [Drawing] no
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Paragraph 0019

(2017/10/05)

Systematic variation of the benzenesulfonamide part of the GluN2A selective NMDA receptor antagonist TCN-201
GluN2A subunit containing N-methyl-D-aspartate receptors (NMDARs) are highly involved in various physiological processes in the central nervous system, but also in some diseases, such as anxiety, depression and schizophrenia. However, the role of GluN2A subunit containing NMDARs in pathological processes is not exactly elucidated. In order to obtain potent and selective inhibitors of GluN2A subunit containing NMDARs, the selective negative allosteric modulator 2 was systematically modified at the benzenesulfonamide part. The activity of the test compounds was recorded in two electrode voltage clamp experiments using Xenopus laevis oocytes expressing exclusively NMDARs with GluN1a and GluN2A subunits. It was found that halogen atoms in 3-position of the benzenesulfonamide part result in high GluN2A antagonistic activity. With an IC50 value of 204?nM the 3-bromo derivative 5i (N-{4-[(2-benzoylhydrazino)carbonyl]benzyl}-3-bromobenzenesulfonamide) has 2.5-fold higher antagonistic activity than the lead compound 2 and represents our new lead compound.
Müller, Sebastian L.,Schreiber, Julian A.,Schepmann, Dirk,Strutz-Seebohm, Nathalie,Seebohm, Guiscard,Wünsch, Bernhard
supporting information
p. 124 - 134
(2017/02/23)

Selective IKur Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide
We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent IKur current blocker with selectivity versus hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further characterization in vivo, compound 1 demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2′ position for a series of close analogues by employing hydrogen bond donors. As a result, 5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide (25) was identified as the lead compound in this series. Compound 25 showed robust effects in rabbit and canine pharmacodynamic models and an acceptable cross-species pharmacokinetic profile and was advanced as the clinical candidate. Further optimization of 25 to mitigate pH-dependent absorption resulted in identification of the corresponding phosphoramide prodrug (29) with an improved solubility and pharmacokinetic profile.
Gunaga, Prashantha,Lloyd, John,Mummadi, Somanadham,Banerjee, Abhisek,Dhondi, Naveen Kumar,Hennan, James,Subray, Veena,Jayaram, Ramya,Rajugowda, Nagendra,Umamaheshwar Reddy, Kommuri,Kumaraguru, Duraimurugan,Mandal, Umasankar,Beldona, Dasthagiri,Adisechen, Ashok Kumar,Yadav, Navnath,Warrier, Jayakumar,Johnson, James A.,Sale, Harinath,Putlur, Siva Prasad,Saxena, Ajay,Chimalakonda, Anjaneya,Mandlekar, Sandhya,Conder, MaryLee,Xing, Dezhi,Gupta, Arun Kumar,Gupta, Anuradha,Rampulla, Richard,Mathur, Arvind,Levesque, Paul,Wexler, Ruth R.,Finlay, Heather J.
p. 3795 - 3803
(2017/05/19)

METHOD FOR MANUFACTURING PYRIDINE-3-SULFONYL CHLORIDE
PROBLEM TO BE SOLVED: To provide a method for manufacturing pyridine-3-sulfonyl chloride easily applicable to an industrial process and capable of providing pyridine-3-sulfonyl chloride by using inexpensive and easily available raw materials with higher yields than conventional ones. SOLUTION: There is provided a method for manufacturing pyridine-3-sulfonyl chloride having a process for adding hydrochloric acid aqueous solution of 3-aminopyridine and an aqueous solution of nitrite to an acidic aqueous solution at a temperature of -30 to -10°C at same time to obtain an aqueous solution of pyridine-3-diazonium salt and a process for adding the resulting aqueous solution of pyridine-3-diazonium salt to a water-insoluble reaction liquid containing sulfurous acid gas, a copper catalyst and a water insoluble organic solvent under stirring to obtain pyridine-3-sulfonyl chloride, where an amount of nitrite based on the amount of 3-aminopyridine is 1 mol equivalent or less. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0023; 0025; 0026

(2017/06/02)

SULFONAMIDE DERIVATIVES, COMPOSITIONS AND METHODS OF USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
Herein, compounds of formula (I), compositions and methods for modulating inclusion formation and stress granules in cells related to the onset of neurodegenerative diseases, musculoskeletal diseases, cancer, ophthalmological diseases, and viral infections are described.
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Page/Page column 73

(2016/06/28)

METHOD FOR PRODUCING SULFONYL CHLORIDE COMPOUND
An object of the present invention is to provide a production method of an intermediate used in the production method of a sulfonylpyrrole compound useful as a pharmaceutical product. The present invention relates to a method of producing sulfonylpyrrole compound (VI) by reacting a pyridine-3-sulfonic acid compound with phosphorus pentachloride in a solvent of chlorobenzene or trifluoromethylbenzene to give a pyridine-3-sulfonyl chloride compound, reacting the compound without isolation with compound (III) to give compound (IV), and subjecting the compound (IV) to a reductive amination reaction. wherein R2 is a hydrocarbon group etc. and R3 and R4 are each a hydrogen atom etc., wherein R1 is an optionally substituted pyridin-3-yl group, and the other symbols are as defined above, wherein R5 is an alkyl group and the other symbols are as defined above.
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Paragraph 01410; 0141; 0145

(2016/01/25)

Method of manufacturing fluorosulfonyl diazidosulfochloride polypyridine-3-
Provided is a pyridine-3-sulfonyl chloride production method which can be applied to industrial processes readily, undergoes the production of a byproduct in a reduced amount, and makes it possible to produce pyridine-3-sulfonyl chloride with higher yield compared with the conventional methods. A pyridine-3-sulfonyl chloride production method comprising the steps of: adding phosphorus pentachloride to a reaction solution containing pyridine-3-sulfonic acid in an amount of less than 1 molar equivalent relative to the amount of pyridine-3-sulfonic acid in multiple divided portions (i) stepwise or (ii) continuously, thereby causing the sequential reaction of pyridine-3-sulfonic acid with phosphorus pentachloride to produce pyridine-3-sulfonyl chloride; and subjecting the reaction solution to distillation under a reduced pressure to purify pyridine-3-sulfonyl chloride.
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Paragraph 0046; 0047

(2016/10/09)

SULFONYLINDOLE DERIVATIVES AND METHOD FOR PREPARING THE SAME
Disclosed are a sulfonylindole derivative useful for the prevention or treatment of pepetic ulcer, gastritis or reflux esophagitis, a method of preparing the same, and a pharmaceutical composition containing the same.
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Paragraph 558; 559; 561; 562; 563

(2015/04/22)

PIPERIDINYL NAPHTHYLACETIC ACIDS
The invention is concerned with the compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and X are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds of formula I are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Paragraph 0194; 0195

(2013/06/27)

Identification of a sirtuin 3 inhibitor that displays selectivity over sirtuin 1 and 2
As part of an effort to identify novel selective modulators of sirtuins, we synthesized and tested several isosteres and constrained analogues of nicotinamide. Biological data suggest that compound 2 is selective for Sirt3 over Sirt1 and Sirt2.
Galli, Ubaldina,Mesenzani, Ornella,Coppo, Camilla,Sorba, Giovanni,Canonico, Pier Luigi,Tron, Gian Cesare,Genazzani, Armando A.
p. 58 - 66,9
(2020/07/31)

Novel Sulfonaminoquinoline Hepcidin Antagonists
The present invention relates to novel hepcidin antagonists, pharmaceutical compositions comprising them and the use thereof as medicaments for the use in the treatment of iron metabolism disorders, such as, in particular, iron deficiency diseases and anemias, in particular anemias in connection with chronic inflammatory diseases.
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Page/Page column 125

(2012/09/05)

Crystal structures of pyridine sulfonamides and sulfonic acids
Despite the widespread occurrence of pyridinesulfonic acid and pyridinesulfonamide functional groups in drugs and pharmaceuticals, and their use as ligands in metal-organic frameworks, a systematic structural study of their hydrogen bonding and molecular packing is lacking. We discuss crystal structures of 2-, 3-, and 4-pyridinesulfonic acids/amides in terms of N +-H???O- hydrogen bonds, N-H???O dimer/catemer synthons, and graph set notations. This model study provides a background for polymorph screening and solid form hunting of pharmacologically active sulfonamides.
Akiri, Kalyanachakravarthi,Cherukuvada, Suryanarayan,Rana, Soumendra,Nangia, Ashwini
p. 4567 - 4573
(2012/11/13)

Efficient and scalable synthesis of pyridine sulfonamides
Short-step and scalable transformations from 2,6-dibromopyridine to 6-bromopyridine-2-sulfonamide by means of halogen-metal exchange and subsequent reaction with sulfuryl chloride followed by amidation are established. Application of the method for the synthesis of various pyridine sulfonamides is also described. Georg Thieme Verlag Stuttgart - New York.
Emura, Takashi,Yoshino, Hitoshi,Tachibana, Kazutaka,Shiraishi, Takuya,Honma, Akie,Mizutani, Akemi,Muraoka, Terushige
experimental part
p. 1117 - 1120
(2011/06/20)

DABCO-bis (sulfur dioxide), DABSO, as a convenient source of sulfur dioxide for organic synthesis: Utility in sulfonamide and sulfamide preparation
The charge-transfer complex generated from the combination of DABCO and sulfur dioxide, DABSO, is a bench-stable colorless solid suitable for use in organic synthesis as a replacement for gaseous sulfur dioxide. The complex can be combined with Grignard reagents to form sulfinates, which can then be converted in situ to a series of sulfonamides. Alternatively, reaction with anilines and iodine leads to the formation of a series of sulfamides. Cheletropic addition between DABSO and 2,3-dimethylbutadiene provides the corresponding sulfolene.
Woolven, Holly,Gonzalez-Rodriguez, Carlos,Marco, Isabel,Thompson, Amber L.,Willis, Michael C.
supporting information; experimental part
p. 4876 - 4878
(2011/12/05)

Directed ortho -metalation-cross-coupling strategies. One-pot Suzuki reaction to biaryl and heterobiaryl sulfonamides
A general synthesis of stable ortho-boropinacolato aryl and heteroaryl sulfonamides by directed ortho-metalation (DoM) and either MeOBPin or i-PrOBpin electrophile quench, 3 → 4, is described. A one-pot metalation-Suzuki cross-coupling procedure for the synthesis of biaryls and heterobiaryls, 3 → 5, and a complementary DoM-Ir-catalyzed boronation sequence (Scheme 6) are delineated.
Schneider, Cedric,Broda, Ellen,Snieckus, Victor
supporting information; experimental part
p. 3588 - 3591
(2011/10/03)

Ring opening of pymisyl-protected aziridines with organocuprates
The pyrimidine-2-sulfonyl (pymisyl) group is introduced as a new protecting group that can be used to activate aziridines towards ring opening. It is readily introduced and removed under mild conditions. Regioselective ring opening of pymisyl-protected 2-methyl-aziridine with organocuprates gives the corresponding sulfonamides in high yields, and the pymisyl group can subsequently be removed upon treatment with a thiolate. The versatility of this new nitrogen protecting group is illustrated with a new synthesis of Selegiline, a monoamine oxidase-B inhibitor marketed for the treatment of Parkinson's disease. Easy on'easy off: The pymisyl group is introduced as a new protecting group for the activation of aziridines towards ring opening with organocuprates (see scheme). It is readily removed under very mild conditions with thiolates. The versatility of the approach is illustrated in a new synthesis of Selegiline, a drug marketed for the treatment of Parkinson's disease.
Bornholdt, Jan,Felding, Jakob,Clausen, Rasmus P.,Kristensen, Jesper L.
supporting information; experimental part
p. 12474 - 12480
(2010/12/25)

Aqueous process chemistry: The preparation of aryl sulfonyl chlorides
The use of aqueous acidic conditions for the preparation of arylsulfonyl chlorides from diazonium salts in the presence of copper salts, preferably CuCl, together with thionyl chloride as the sulfur dioxide source, has considerable advantages over recommended literature procedures, whereby reactions are carried out in acetic acid with minimisation of water content of the solvent. The method has been shown to be successful for a wide range of electron-deficient and electron-neutral aryl substrates. The sulfonyl chlorides are protected from hydrolysis by their low solubility in water, which results in their direct precipitation from the reaction mixture in good yields (>70%) and high strength (>98% w/w). The aqueous process, which is additionally safer and more robust, can be readily scaled up and has significant environmental benefits.
Hogan, Philip J.,Cox, Brian G.
experimental part
p. 875 - 879
(2010/04/22)

8-SULFONYL-L, 3, 4, 8-TETRAHYDR0-2H- [1, 4] OXAZEPINO [6, 7-E] INDOLE DERIVATIVES AND THEIR USE AS 5-HT6 RECEPTOR LIGANDS
The present invention relates to compounds of the formula (I) wherein A, X and R1 to R9 are as described herein; to pharmaceutical compositions comprising the said compounds; to processes for their preparation; and to the use of the compounds as medicaments against 5-HT6 receptor-related disorders.
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Page/Page column 90

(2008/12/05)

2- [ (2-SUBSTITUTED) -IND0LIZIN-3-YL] -2-OXO-ACETAMIDE DERIVATIVES AS ANTIFUNGAL AGENTS
The invention provides compounds of formula (I), and pharmaceutically acceptable salts thereof wherein: Rl, R2, R3, R4, R5, R6, R7, X and X1 are as defined herein. These compounds are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
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Page/Page column 114

(2008/12/05)

From haloquinolines and halopyridines to quinoline- and pyridinesulfonyl chlorides and sulfonamides
The action of sodium methanethiolate (in boiling DMF) towards haloazines (i.e. chloro- or bromo-pyridines and quinolines) (1) (with halogen substituent in non-aza-activated position) causes sequentially halogen ipso-substitution to methylthioazines (2) and then S-demethylation to azinethiolates (3A), which were: i) subjected to S-methylation, ii) oxidized to diazinyl disulfides (4) and iii) oxidatively chlorinated to azinesulfonyl chlorides (5). α- and γ-pyridine- and quinolinesulfonyl chlorides (5a, 5c, 5d and 5f) were prepared by oxidative chlorination of respective disulfides (4) performed in conc. hydrochloric acid and characterized by 1H and 13C NMR spectra. All azinesulfonyl chlorides (5) were effectively converted to corresponding azinesulfonamides (6).
Maslankiewicz, Andrzej,Marciniec, Krzysztof,Pawlowski, Maciej,Zajdel, Pawel
p. 1975 - 1990
(2008/09/16)

Acetylenyl-pyrazolo-pyrimidine derivatives
The present invention relates to compounds of formula (I): wherein R1 to R3, A, M, L, E, G, and J are as defined in the description and claims. The invention also relates to a process for the manufacture of such compounds, pharmaceutical compositions containing them, and methods for treating CNS disorders.
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Page/Page column 25

(2008/06/13)

Multimeric VLA-4 antagonists comprising polymer moieties
Disclosed are conjugates which bind VLA-4. Certain of these conjugates also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such conjugates are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The conjugates can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.
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Page/Page column 55

(2010/02/15)

IMIDAZOLONE PHENYLALANINE DERIVATIVES AS VLA-4 ANTAGONISTS
Disclosed are compounds of the f ormula : and the pharmaceutically acceptable salts thereof wherein the variables A, n, R5, R21-R24 and Q are defined herein. These compounds bind VLA-4. Certain of these compound also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.
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Page/Page column 60; 75-77

(2010/11/25)

Acetyl-CoA carboxylase inhibitors
Acetyl Coenzyme A Carboxylase inhibitors, pharmaceutical compositions containing such compounds and the use of such compounds to treat for example, Metabolic Syndrome including atherosclerosis, diabetes and obesity.
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(2008/06/13)

Facile one-pot synthesis of aromatic and heteroaromatic sulfonamides
A series of arene and heteroarene sulfonamides were prepared in one vessel from aryl and heteroaryl bromides via conversion into the corresponding Grignard reagents using either magnesium or isopropylmagnesium chloride and subsequent reaction with sulfur dioxide, sulfuryl chloride, and an amine.
Pandya, Rina,Murashima, Takashi,Tedeschi, Livio,Barrett, Anthony G. M.
p. 8274 - 8276
(2007/10/03)

4-AMINOPYRROLOPYRIMIDINES AS KINASE INHIBITORS
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(2008/06/13)

Substituted anilides
The invention is directed to physiologically active compounds of formula (I): wherein: R1is hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy; X1, X2and X6independently represent N or CR10; and one of X3, X4and X5represents CR11and the others independently represents N or CR10; where R10is hydrogen, amino, halogen, hydroxy, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulphinyl, lower alkylsulphonyl, nitro or trifluoromethyl; and R11represents a group —L1—Ar1—L2—Y; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (α4β1).
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(2008/06/13)

3-AMINOPIPERIDINE DERIVATIVES AS INTEGRIN γ(a)vγ(b)3 ANTAGONISTS
An object of the present invention is to provide novel derivatives having integrin αvβ3 antagonistic activity wherein a basic atomic group has been attached to the 3-position of a piperidine ring either directly or through various atomic groups. The derivatives according to the present invention are compounds represented by formula (I) or pharmaceutically acceptable salts or solvates thereof, which are useful for the treatment or prevention of cardiovascular diseases, angiogenesis-related diseases, cerebrovascular diseases, cancers and metastasis thereof, immunological diseases, osteopathy and other diseases: wherein A represents an optionally substituted heterocyclic group containing at least one nitrogen atom, a bicylic group or the like; D represents a bond, >NR4, >CR5R6, O, S, or -NR4-CR5R6-; Z represents CH or N; R7 and R8 represent hydroxyl, alkyl or the like; Q represents >C=O or the like; R9 represents hydrogen, alkyl or the like; J represents a bond or alkylene; R10 represents optionally substituted hydroxyl, amino or the like; R11 represents hydrogen, alkyl or the like; m is 0 to 5; n is 0 to 4; p is 3 or 4; and q is 0 to 3.
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(2008/06/13)

Bispiperidines as antithrombotic agents
Novel compounds which are inhibitors of the binding of fibrinogen to the Gp IIb/IIIa platelet receptors, and which can be used therepeutically as antithrombotic agents
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(2008/06/13)

Non-peptide GPIIb/IIIa inhibitors. 20. Centrally constrained thienothiophene α-sulfonamides are potent, long acting in vivo inhibitors of platelet aggregation
The synthesis and pharmacology of 4, a potent thienothiophene non- peptide fibrinogen receptor antagonist, are reported. Compound 4 inhibited the aggregation of human gel-filtered platelets with an IC50 of 8 nM and demonstrated an 8-fold improvement in affinity for isolated GPIIb/IIIa receptors over analogues possessing an isoindolinone backbone. Flow cytometry studies revealed that the binding of 4 to resting platelets is a diffusion- controlled process (k(on) = 3.3 x 106 M-1 s-1) and that 4 binds to dog and human platelets with comparable affinity (K(d) = 0.04 and 0.07 nM, respectively). Ex vivo platelet aggregation in dogs was completely inhibited by an iv dose of 5 mg/kg, and an oral dose of 50-90 mg/kg followed by low daily doses of 10 mg/kg was sufficient to maintain ~80% inhibition of ex vivo platelet aggregation over several days. Inhibition of ADP-induced platelet aggregation in anesthetized dogs at 77 ± 7% resulted in a moderate 2.5-fold increase in bleeding time, while complete inhibition (100%) resulted in an approximately 10-min bleeding time. Additional doses were required to increase the bleeding time to the maximum time allowed in the protocol (15 min), thus indicating a potentially useful and safe separation of efficacy and bleeding time.
Egbertson, Melissa S.,Cook, Jacquelynn J.,Bednar, Bohumil,Prugh, John D.,Bednar, Rodney A.,Gaul, Stanley L.,Gould, Robert J.,Hartman, George D.,Homnick, Carl F.,Holahan, Marie A.,Libby, Laura A.,Lynch Jr., Joseph J.,Lynch, Robert J.,Sitko, Gary R.,Stranieri, Maria T.,Vassallo, Laura M.
p. 2409 - 2421
(2007/10/03)

Alpha IC adrenergic receptor antagonists
This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as selective alpha-1C adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hypertrophy. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha1C receptor subtype without at the same time inducing orthostatic hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.
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(2008/06/13)

Compounds and methods for identifying activated platelets
The invention is directed to a series of novel compounds, and their pharmaceutically acceptable salts, of the formula STR1 wherein R is C0-6 alkyl substituted with R5 or a mono or polycyclic aromatic or heteroaromatic system comprised of 5 or 6-membered aromatic or heteroaromatic rings that are either unsubstituted or substituted with one or more of R1 and R2 ; R1 and R2 are independently C1-6 alkyl, carboxyl, hydroxyl, azido, nitro, amino, C1-6 alkylamino, C1-6 dialkylamino, arylamino, aryl C1-6 alkylamino, hydroxysulfonyl or arylazo; aryl is a phenyl or naphthyl ring which is unsubstituted or substituted with one or more of R3 and R4 ; R3 and R4 are independently C1-6 alkyl, azido, nitro, amino, C1-6 dialkylamino or hydroxysulfonyl; R5 is STR2 provided that when R is an unsubstituted monocyclic ring, the monocyclic ring is not phenyl or pyridyl. Such compounds are useful as fluorescent probes for identifying antiplatelet agents which selectively bind to activated platelets.
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(2008/06/13)

4-HYDROXY-BENZOPYRAN-2-ONES AND 4-HYDROXY-CYCLOALKYL[B]PYRAN-2-ONES USEFUL TO TREAT RETROVIRAL INFECTIONS
The present invention relates to compounds of formula I which are 4-hydroxy-benzopyran-2-ones and 4-hydroxy-cycloalkyl[b]pyran-2-ones useful for inhibiting a retrovirus in a mammalian cell infected with said retrovirus. STR1 Wherein R 10 and R 20 taken together are: STR2
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(2008/06/13)

Fibrinogen receptor antagonists
Fibrinogen receptor antagonists having the formula STR1 for example STR2
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(2008/06/13)

Fibrinogen receptor antagonists
Fibrinogen receptor antagonists of the formula: STR1 are disclosed for use in inhibiting the aggregation of blood platelets. wherein G is: STR2
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(2008/06/13)

Symmetrical and unsymmetrical quadruply Aza bridged closely interspaced cofacial Bis(5,10,15,20-tetraphenylporphyrin)s. 2. Synthesis, characterization, and conformational effects of solvents
Several water- and non-water-soluble symmetrical and unsymmetrical quadruply aza bridged closely interspaced cofacial bis(5,10,15,20-tetraphenylporphyrin)s have been synthesized and fully characterized by 2D 1H-1H NMR (COSY), 2D 13C-1H NMR, FABMS, UV/vis, IR, and fluorescence spectral techniques. It was established, on the basis of 1H NMR, UV/vis, and emission spectrophotometries, that tetrakis[m,m-(methylene(m-pyridinesulfonyl)imino)methylene]-strati-bis-(5,10,15, 20-tetraphenylporphyrin) (5), tetrakis[m,m-(methylene(m-pyridiniumsulfonyl)imino)methylene]-strati-bis-(5,10, 15,20-tetraphenylporphyrin) chloride (7), and tetrakis[m,m-(methylene(p-toluenesulfonyl)imino)methylene]-strati-bis(5,10,15, 20-tetraphenylporphyrin) (11) exist in more than one conformation in DMSO and in only one symmetrical conformation in CHCl3. The biszinc and tetraprotonated 5, 7, and 11 exist in one conformation regardless of the solvent. These observations have been attributed to an interaction between DMSO and the pyrrolic N-H protons of the porphyrin cores which is inhibited by metalation (Zn2+) or protonation of the porphyrin moiety. Molecular dynamics calculations reveal that the intracavity interactions of 5 with DMSO are more important than the intercavity interactions which result in discrete, unsymmetrical conformations of the dimer. In contrast, tris[m,m-(methylene(m-pyridinesulfonyl)imino)methylene]-mono((((methyleneoxy) carbonyl)oxy)methylene)-strati-bis(5,10,15,20-tetraphenylporphyrin) (6), tetrakis[m,m-(methylenecyanoimino)-methylene]-strati-bis(5,10,15,20- tetraphenylporphyrin) (8), tris[m,m-(methylenecyanoimino)methylene]-mono((((methyleneoxy)carbonyl)oxy) methylene)-strati-bis(5,10,15,20-tetraphenylporphyrin) (9), and tetrakis[m,m-(methylene(formainido)imino)methylene]-strati-bis(5,10,15,20- tetraphenylporphyrin) (10) do not show any conformational changes upon switching from chloroform to DMSO. This is attributed to the long interplanar distances calculated for the porphyrin dimers which prevent any intracavity coordination of DMSO with both porphyrin moieties. 1H NMR variable-temperature experiments of porphyrin dimer 5 in DMSO show that the conformation of the dimer is greatly affected by temperature. While at room temperature 5 exists in more than one conformation, at higher temperatures (150 °C) only one conformation is populated. It is proposed that at room temperature, the existence of a hydrogen-bonding network between DMSO and the dimer results in more than one conformation, while at higher temperatures the network is destroyed to furnish an average conformation.
Karaman, Rafik,Blaskó, Andrei,Almarsson, ?rn,Arasasingham, Ramesh,Bruice, Thomas C.
p. 4889 - 4898
(2007/10/02)

Directed Metalation of Pyridinesulphonamides. Synthesis of Pyridine-fused Isothiazoles and 1,2-Oxathioles
4-Lithio-N-t-butylpyridine-3-sulphonamide reacted with benzophenone and carbon dioxide respectively to give the corresponding intermediates which on appropriate treatment gave isothiazolo-3-one 1,1-dioxides.Metalation of 2- and 4-(N,N-dialkylaminosulphonyl)pyridines with lithium diisopropylamide (LDA) gave anions which reacted with benzophenone to give carbinols which thermally cyclised to 1,2-oxathiolopyridine and 1,2-oxathiolopyridine respectively.
Alo, Babajide I.,Familoni, Oluwole B.,Marsais, Francis,Queguiner, Guy
p. 61 - 64
(2007/10/02)

Synthesis and Characterization of the First Water-Soluble Closely Interspaced Cofacial Porphyrin Dimer
The first closely spaced quadruply bridged water-soluble cofacial dimer (5) was succesfully synthesized by the reaction of porphyrin 2 with sulfonamide 3 followed by N-methylation with methyl iodide.The conformations of 5 and its precursor 4 are largely dependent on the solvent, and the solvent effect is inhibited by protonation or metalation of the porphyrin cores.
Karaman, Rafik,Bruice, Thomas R.
p. 3470 - 3472
(2007/10/02)

Formation of Olefins via Pyrolysis of Sulfonate Esters
Esters of 8-quinolinesulfonic acid and 2-pyridinesulfonic acid were synthesized from alcohols and the acid chlorides.The secondary esters decomposed cleanly at moderate temperatures to give olefins in hight yield.Product studies were consistent with carbocation formation and abstraction by a ring nitrogen to give olefin.The importance of a basic group was confirmed by pyrolysis of a series of para-substituted cyclohexyl benzenesulfonates, p-XC6H4SO3R.The compounds with X=NHEt and NHCOMe reacted cleanly to give olefin in good yield.When X = NO2, Br, CH3, or OCH3, olefin was formed in low yield along with considerable amounts of tar.
Corey, E. J.,Posner, Gary H.,Atkinson, Richard F.,Wingard, Astrid K.,Halloran, Daniel J.,et al.
p. 389 - 393
(2007/10/02)

Benzoquinolizines as α2 -adrenoceptor antagonists
The invention concerns benzoquinolizines of general formula STR1 and their pharmaceutically acceptable acid addition salts. In the formula R 1 and R 2 which may be the same or different each represent hydrogen, lower alkyl, lower alkoxy or halogen, R 3 represents hydrogen or lower alkyl and R 4 represents a heterocyclic radical attached to the SO 2 group through a carbon atom of the heterocyclic ring. The compounds possess α 2 -adrenoceptor antagonistic activity in warm blooded animals.
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(2008/06/13)