186552-07-8

Upstream product

• 73305-93-8 4-methylthiophene-2-carbonitrile 
• 558-13-4 carbon tetrabromide 
• 603-35-0 triphenylphosphine 
• 186552-06-7 4-(hydroxymethyl)thiophene-2-carbonitrile 
• 498-62-4 3-thiophene carboxaldehyde 
• 18799-85-4 5-iodo-thiophene-3-carboxaldehyde 
• 185395-90-8 (5-iodo-thiophene-3-yl)methanol 

Downstream Products

• 1027481-51-1 (S)-1-((R)-2-Amino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid (5-cyano-thiophen-3-ylmethyl)-amide 
• 1027227-14-0 ((R)-1-{(S)-2-[(5-Cyano-thiophen-3-ylmethyl)-carbamoyl]-pyrrolidine-1-carbonyl}-2,2-diphenyl-ethyl)-carbamic acid methyl ester 
• 1025879-96-2 C₂₆H₂₇N₅O₄S₂ 
• 1026963-96-1 ((R)-1-{(S)-2-[(5-Cyano-thiophen-3-ylmethyl)-carbamoyl]-pyrrolidine-1-carbonyl}-2,2-diphenyl-ethylamino)-acetic acid tert-butyl ester 
• 186549-27-9 RPR120844 
• 280781-47-7 (S)-1-((R)-2-Methanesulfonylamino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid (5-cyano-thiophen-3-ylmethyl)-amide 
• 232280-77-2 4-aminomethyl-thiophene-2-carbonitrile 

Relevant academic research and scientific papers

N-(HETEROARYL)-SULFONAMIDE DERIVATIVES USEFUL AS S100-INHIBITORS

A compound of formula (I), or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the compound. The compound is an inhibitor of interactions between S100A9 and interaction partners such as RAGE, TLR4 and EMMPRIN and as such is useful in the treatment of disorders such as cancer, autoimmune disorders, inflammatory disorders and neurodegenerative disorders.

Thrombin inhibitors

Novel five-membered heterocyclic amidines, their preparation and use as competitive inhibitors of trypsin-like serine proteases, especially thrombin and kininogenases such as kallikrein. Pharmaceutical compositions which contain the compounds as active ingredients, and use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents.

THROMBIN INHIBITORS

The present invention relates to a compound having formula I:and pharmaceutically acceptable salts thereof. The compounds of formula I and pharmaceutical compositions containing them are of the class of thrombin inhibitors which are useful as anticoagulants.

Efficacious and orally bioavailable thrombin inhibitors based on a 2,5-thienylamidine at the P1 position: Discovery of N-carboxymethyl-D-diphenylalanyl-L-prolyl[(5-amidino-2- thienyl)methyllamide

Thrombin, a crucial enzyme in the blood coagulation, has been a target for antithrombotic therapy. Orally active thrombin inhibitors would provide effective and safe prophylaxis for venous and arterial thrombosis. We conducted optimization of a highly efficacious benzamidine-based thrombin inhibitor LB30812 (3, Ki = 3 pM) to improve oral bioavailability. Of a variety of arylamidines investigated at the P1 position, 2,5-thienylamidine effectively replaced the benzamidine without compromising the thrombin inhibitory potency and oral absorption. The sulfamide and sulfonamide derivatization at the N-terminal position in general afforded highly potent thrombin inhibitors but with moderate oral absorption, while the well-absorbable N-carbamate derivatives exhibited limited metabolic stability in S9 fractions. The present work culminated in the discovery of the N-carboxymethyl- and 2,5-thienylamidine-containing compound 22 that exhibits the most favorable profiles of anticoagulant and antithrombotic activities as well as oral bioavilability (Ki = 15 pM; F = 43%, 42%, and 15% in rats, dogs, and monkeys, respectively). This compound on a gravimetric basis was shown to be more effective than a low molecular weight heparin, enoxaparin, in the venous thrombosis models of rat and rabbit. Compound 22 (LB30870) was therefore selected for further preclinical and clinical development.

Noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1

A series of noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1 was investigated. While the amidrazone and the amine series displayed limited oral absorption, the amidine series demonstrated generally good oral absorption and strong antithrombotic activity; the single-digit picomolar Ki achieved from this series is among the best yet reported. The present work highlights the benzamidine compound 11f (LB30812) that exhibits excellent overall profiles of potency, oral absorption and antithrombotic efficacy.

Thrombin inhibitors

The present invention relates to a compound having formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I and pharmaceutical compositions containing them are of the class of thrombin inhibitors which are useful as anticoagula

Substituted sulfonic acid N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds

The compounds of formula I exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More specifically, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, which are for treating a patient suffering from, or subject to, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.

Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa

The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(s)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (K1 = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.

SUBSTITUTED SULFONIC ACID N-[(AMINOIMINOMETHYL)PHENYLALKYL]-AZAHETEROCYCLAMIDE COMPOUNDS

The compounds of formula I exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More specifically, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, which are for treating a patient suffering from, or subject to, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.