التفاصيل البيبلوغرافية
| العنوان: |
Synthesis of thienopyridinone compounds and related intermediates |
| Document Number: |
20060084805 |
| تاريخ النشر: |
April 20, 2006 |
| Appl. No: |
11/269042 |
| Application Filed: |
November 08, 2005 |
| مستخلص: |
The invention relates to 5-HT receptor agonists and partial agonists. Novel thienopyridinone compounds represented by Formula I, and synthesis and uses thereof for treating diseases mediated directly or indirectly by 5-HT receptors, are disclosed. Such conditions include Alzheimer's disease, cognition disorders, irritable bowel syndrome, nausea, emesis, vomiting, prokinesia, gastroesophageal reflux disease, nonulcer dyspepsia, depression, anxiety, urinary incontinence, migraine, arrhythmia, atrial fibrillation, ischemic stroke, gastritis, gastric emptying disorders, feeding disorders, gastrointestinal disorders, constipation, erectile dysfunction, and respiratory depression. Methods of preparation and novel intermediates and pharmaceutical salts thereof are also included. |
| Inventors: |
Dhanoa, Dale S. (Wakefield, MA, US); Becker, Oren (Mevaseret Zion, IL); Noiman, Silvia (Herzliya, IL); Mohanty, Pradyumna (Woburn, MA, US); Chen, Dongli (Chestnut Hill, MA, US); Lobera, Mercedes (Concord, MA, US); Wu, Laurence (Woburn, MA, US); Marantz, Yael (Kadima, IL); Inbal, Boaz (Kfar Shmuel, IL); Heifetz, Alexander (Bnei-Brak, IL); Bar-Haim, Shay (Netanya, IL); Shacham, Sharon (Alfey Menashe, IL) |
| Claim: |
1. A method for making a compound of the formula, [chemical expression included] wherein R1 and R2 are H; and R3 and R4 are independently selected from the group consisting of methyl, ethyl and isopropyl, comprising the steps of a) preparing an alkylated product by reductive alkylation of a substituted or unsubstituted aminothiophene-3-carboxylate with an aldehyde or a ketone; b) hydrolyzing the alkylated product; c) reacting the hydrolyzed alkylated product with triphosgene to form a highly reactive anhydride; and d) thermally reacting the highly reactive anhydride with diethyl malonate under basic conditions. |
| Claim: |
2. A method for making a compound of the formula, [chemical expression included] wherein R1 and R2 are H; and R3 and R4 are independently selected from the group consisting of methyl, ethyl and isopropyl, comprising the steps of a) preparing an alkylated product by reductive alkylation of a substituted or unsubstituted aminothiophene-3-carboxylate with an aldehyde or a ketone; b) forming an amide by reaction of the alkylated product with ethyl 3-chloro-3-oxoproprionate and triethylamine; and c) carrying out an intramolecular condensation reaction under basic conditions. |
| Claim: |
3. A compound having the formula [chemical expression included] wherein R1 and R2 are H; and R3 and R4 are independently selected from the group consisting of methyl, ethyl and isopropyl. |
| Claim: |
4. The compound of claim 2, wherein R3 is isopropyl. |
| Claim: |
5. Methyl 6,7-dihydro-4-hydroxy-7-isopropyl-6-oxothieno-[2,3-b]pyridine-5-carboxylate. |
| Claim: |
6. A method for making a compound of the formulae [chemical expression included] wherein R1 is ethyl or isopropyl; and R2 is an optionally substituted alkyl group selected from the group consisting of ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, pentyl, methylcyclopropyl, isopropanol, phenylethyl; or [chemical expression included] wherein R1 is (C1-C8) branched or unbranched alkyl; a (C1-C8) substituted or unsubstituted carbocyclic ring; branched or unbranched haloalkyl, a substituted or unsubstituted aryl or heteroaryl ring, or a substituted or unsubstituted (CH2)p-aryl or (CH2)p-heteroaryl ring, where p is 1, 2, 3, or 4; R2 and R3, taken together, form a substituted or unsubstituted piperidine, pyrrolidine, azepane, aziridine, or azetidine ring; and n is 1, 2, 3, 4, 5 or 6; the method comprising the steps of heating in an organic solvent a mixture comprising a substituted or unsubstituted piperidinyl alkylamine and an intermediate having the formula [chemical expression included] wherein R1 and R2 are H; and R3 and R4 are independently selected from the group consisting of methyl, ethyl and isopropyl. |
| Claim: |
7. The method of claim 6, wherein the intermediate is methyl 6,7-dihydro-4-hydroxy-7-isopropyl-6-oxothieno-[2,3-b]pyridine-5-carboxylate. |
| Current U.S. Class: |
546114/000 |
| Current International Class: |
07 |
| رقم الانضمام: |
edspap.20060084805 |
| قاعدة البيانات: |
USPTO Patent Applications |