- From 2,6-dichloronicotinic acid to thiopeptide cores
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The scope of 2,6-dichloronicotinic acid as a precursor of thiopeptide polyheterocylic cores has been extensively studied in a cross-coupling-based approach. Differentiation of the two chlorinated positions under SNAr conditions and versatility of the carboxylic acid are key for the preparation of 2,3,6-trisubstituted pyridines with complete regiocontrol. With the present strategy, nine different azole-substituted pyridines were synthesized. Studies towards the selective deprotection of their functionalities resulted in a set of fully orthogonal protecting groups that permits the elongation of all three pyridine substituents. Copyright
- Just-Baringo, Xavier,Albericio, Fernando,Alvarez, Mercedes
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Read Online
- SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS
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Disclosed are compounds of Formula (I) N-oxides, or salts thereof, wherein X, Y, A, G, R1, and R5 are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.
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Page/Page column 212-213
(2021/04/10)
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- INDOLE COMPOUNDS AND THEIR USE
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The present disclosure relates to indole compounds and pharmaceutical compositions thereof, and their use in stimulating the immune system of patients in need thereof and in treating cancer.
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Paragraph 00191; 00192
(2019/06/05)
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- Optimization of Novel 1-Methyl-1 H-Pyrazole-5-carboxamides Leads to High Potency Larval Development Inhibitors of the Barber's Pole Worm
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A phenotypic screen of a diverse library of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of a 1-methyl-1H-pyrazole-5-carboxamide derivative with an IC50 of 0.29 μM. Medicinal chemistry optimization targeted modifications on the left-hand side (LHS), middle section, and right-hand side (RHS) of the scaffold in order to elucidate the structure-activity relationship (SAR). Strong SAR allowed for the iterative and directed assembly of a focus set of 64 analogues, from which compound 60 was identified as the most potent compound, inhibiting the development of the fourth larval (L4) stage with an IC50 of 0.01 μM. In contrast, only 18% inhibition of the mammary epithelial cell line MCF10A viability was observed, even at concentrations as high as 50 μM.
- Le, Thuy G.,Kundu, Abhijit,Ghoshal, Atanu,Nguyen, Nghi H.,Preston, Sarah,Jiao, Yaqing,Ruan, Banfeng,Xue, Lian,Huang, Fei,Keiser, Jennifer,Hofmann, Andreas,Chang, Bill C. H.,Garcia-Bustos, Jose,Jabbar, Abdul,Wells, Timothy N. C.,Palmer, Michael J.,Gasser, Robin B.,Baell, Jonathan B.
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p. 10875 - 10894
(2019/01/04)
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- Utilization of an Active Site Mutant Receptor for the Identification of Potent and Selective Atypical 5-HT2C Receptor Agonists
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Agonism of the 5-HT2C receptor represents one of the most well-studied and clinically proven mechanisms for pharmacological weight reduction. Selectivity over the closely related 5-HT2A and 5-HT2B receptors is critical as their activation has been shown to lead to undesirable side effects and major safety concerns. In this communication, we report the development of a new screening paradigm that utilizes an active site mutant D134A (D3.32) 5-HT2C receptor to identify atypical agonist structures. We additionally report the discovery and optimization of a novel class of nonbasic heterocyclic amide agonists of 5-HT2C. SAR investigations around the screening hits provided a diverse set of potent agonists at 5-HT2C with high selectivity over the related 5-HT2A and 5-HT2B receptor subtypes. Further optimization through replacement of the amide with a variety of five- and six-membered heterocycles led to the identification of 6-(1-ethyl-3-(quinolin-8-yl)-1H-pyrazol-5-yl)pyridazin-3-amine (69). Oral administration of 69 to rats reduced food intake in an ad libitum feeding model, which could be completely reversed by a selective 5-HT2C antagonist.
- Carpenter, Joseph,Wang, Ying,Wu, Gang,Feng, Jianxin,Ye, Xiang-Yang,Morales, Christian L.,Broekema, Matthias,Rossi, Karen A.,Miller, Keith J.,Murphy, Brian J.,Wu, Ginger,Malmstrom, Sarah E.,Azzara, Anthony V.,Sher, Philip M.,Fevig, John M.,Alt, Andrew,Bertekap, Robert L.,Cullen, Mary Jane,Harper, Timothy M.,Foster, Kimberly,Luk, Emily,Xiang, Qian,Grubb, Mary F.,Robl, Jeffrey A.,Wacker, Dean A.
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p. 6166 - 6190
(2017/08/02)
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- As opioid receptor antagonists or inverse agonists of the novel compounds
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Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
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Paragraph 0368; 0369
(2016/10/08)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
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Paragraph 1233
(2015/02/18)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
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Page/Page column 270
(2015/02/02)
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- Concise synthesis and X-ray crystal structure of N -benzyl-2-(pyrimidin-4'- ylamino)-thiazole-4-carboxamide (Thiazovivin), a small-molecule tool for stem cell research
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Stem cell research is one of the most promising fields of modern biomedical research and regenerative medicine. Limited availability and ethical concerns suggest the renouncement of embryonic stem cells (ESCs), thus raising the need for more efficient pro
- Ries, Oliver,Granitzka, Markus,Stalke, Dietmar,Ducho, Christian
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supporting information
p. 2876 - 2882
(2013/09/02)
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- NOVEL COMPOUNDS AS ANTAGONISTS OR INVERSE AGONISTS AT OPIOID RECEPTORS
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Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
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- METHOD OF TREATMENT USING NOVEL ANTAGONISTS OR INVERSE AGONISTS AT OPIOID RECEPTORS
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A method of treatment using pharmaceutical compositions containing novel antagonists or inverse agonists at opioid receptors for the treatment of binge eating disorder, anorexia nervosa, bulimia nervosa, excess drug or alcohol use, or eating disorder not otherwise specified.
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- Concise total synthesis of the thiazolyl peptide antibiotic GE2270 A
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The potent antibiotic thiazolylpeptide GE2270 A was synthesized starting from N-tert-butyloxycarbonyl protected valine in a longest linear sequence of 20 steps and with an overall yield of 4.8 %. Key strategy was the assembly of the 2,3,6-trisubstituted p
- Delgado, Oscar,Martin Mueller,Bach, Thorsten
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experimental part
p. 2322 - 2339
(2009/04/10)
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- AZAADAMANTANE ESTER AND CARBAMATE DERIVATIVES AND METHODS OF USE THEREOF
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The invention relates to compounds that are substituted azaadamantane ester and carbamate derivatives, compositions comprising such compounds, and methods of using such compounds and compositions.
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Page/Page column 67
(2008/12/04)
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- AZAADAMANTANE DERIVATIVES AND METHODS OF USE
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The invention relates to compounds that are azaadamantane derivatives, particularly ether- or amine-substituted azaadamantane derivatives and salts and prodrugs thereof, compositions comprising such compounds, methods of using such compounds and compositi
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Page/Page column 171-172
(2008/12/06)
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- HETEROCYCLIC NON-PEPTIDE GNRH ANTAGONISTS
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A compound of formula (I): wherein either B is absent and A and Z are the same or different and are each hydrogen, halogen, alkyl, hydroxy, alkoxy,-CN,-C(Rc)2OH,-N(Rd)C(=X)Rc,-C(=X)N(Rc)(Rd),-S(O)m-Rc,-N(Rc)(Rd)S(O)2,-S(O)2N(R c)(Rd),-N(Re)2, aryl optionally substituted with Ra or-O-aryl optionally substituted with Ra; or B is present and is-(CH2)n-,-C(Rb)2-or-O-, or B taken together with A or Z can be-C=C(Rb)-,-C(Rb)=C-,-CH2-CH(R b)-or-CH(Rb)-CH2-; D is-O-or-S(O) m,-; E is a bond or is-(CH2)n-,-N(R d)-,-(CH2)nN(Rd)-or-N(R d)(CH2)n-; F is-C(=X)-; G is-(CH2 )n-,-N(Rd)-,-(CH2)nN(R d)-or-N(Rd)(CH2)n; J is a bond,-O-,-N(RC)C(=X)-,-C(=X)N(Rc)-,-S(O)m,-,-N(Rc)S(O)m-,-S(O)nN(Rc)-,-N(Re)-or-N(Rg)(Rh); K is a bond, alkylene, cycloalkylene, cycloalkenylene, arylene, heterocycloalkylene, heterocycloalkylene or heteroarylene; and L is hydrogen or a terminal group; has therapeutic utility.
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Page/Page column 61
(2008/06/13)
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- Thiazoles as inhibitors of 11B-hydroxysteroid dehydrogenase
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, type II diabetes mellitus and metabolic syndrome.
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Page/Page column 16-17
(2008/06/13)
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- 4-[(4-(CARBOXYETHYL) PIPERIDINYL) METHYL] PYRROLIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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3-Substituted pyrrolidines having a 4-carboxypiperidinylmethyl substituent on the 4-position of the ring are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.
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- Protease inhibitors
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The present invention provides compounds of formula (I) which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia or malignancy; and metabolic bone disease therewith.
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- 5,6,7,8-tetrahydropyrido[2,3-D]pyrimidines
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PCT No. PCT/US96/14822 Sec. 371 Date Feb. 26, 1999 Sec. 102(e) Date Feb. 26, 1999 PCT Filed Sep. 17, 1996 PCT Pub. No. WO97/41115 PCT Pub. Date Nov. 6, 1997Glutamic acid derivatives in which the amino group is substituted with a 2-amino-5,6,7,8-tetrahydro
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