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The present invention relates to novel bicyclic benzamide derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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In one aspect this invention relates generally to compounds of Formula: and sub-formulas thereof, or a tautomer of each thereof, a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, where X1, L1, L3, and R3 are described herein.

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Novel 2-aminooctahydrocyclopentalene-3a-carboxamides as potent CCR2 antagonists

Novel CCR2 antagonists with a novel 2-aminooctahydrocyclopentalene-3a- carboxamide scaffold were designed. SAR studies led to a series of potent compounds. For example, compound 51 had a good PK profile in both dog and monkey, and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice. In addition, an asymmetric synthesis to the core structures was developed.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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SUBSTITUTED SPIROAMIDE COMPOUNDS

Substituted spiroamide compounds corresponding to formula (I): wherein A, B, Q1, Q2, Q3, Q4, R1, R8, R9a, R9b, R12, R13, R200 and R210 have defined meanings, processes for their preparation, pharmaceutical compositions containing such compounds, and the use of such compounds for treating or inhibiting pain or other conditions mediated at least in part by the bradykinin 1 receptor (B1R)

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Tetrahydroisoquinoline – Wikipedia,
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Arylmethoxy Isoindoline Derivatives and Compositions Comprising and Methods of Using the Same

Provided are 4?-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

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Design and synthesis of trans-N-[4-[2-(6-cyano-1,2,3,4- tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (SB- 277011): A potent and selective dopamine D3 receptor antagonist with high oral bioavailability and CNS penetration in the rat

A selective dopamine D3 receptor antagonist offers the potential for an effective antipsychotic therapy, free of the serious side effects of currently available drugs. Using clearance and brain penetration studies as a screen, a series of 1,2,3,4-tetrahydroisoquinolines, exemplified by 13, was identified with high D3 affinity and selectivity against the D2 receptor. Following examination of molecular models, the flexible butyl linker present in 13 was replaced by a more conformationally constrained cyclohexylethyl linker, leading to compounds with improved oral bioavailability and selectivity over other receptors. Subsequent optimization of this new series to improve the cytochrome P450 inhibitory profile and CNS penetration gave trans-N[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4- quinolinecarboxamide (24, SB-277011). This compound is a potent and selective dopamine D3 receptor antagonist with high oral bioavailability and brain penetration in the rat and represents an excellent new chemical tool for the investigation of the role of the dopamine D3 receptor in the CNS.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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MODULATORS OF TOLL-LIKE RECEPTORS

Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds

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Tetrahydroisoquinoline – Wikipedia,
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7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK and F 29661, 1) is a potent inhibitor of the enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). In contrast to other inhibitors of PNMT, it is also highly selective toward PNMT in comparison with its affinity toward the alpha2- adrenoceptor (PNMT K(i) = 0.55 muM, alpha2 K(i) = 100 muM, selectivity [alpha2 K(i)/PNMT K(i)] = 180). A diverse set of compounds was synthesized and evaluated to probe the role of the acidic hydrogen of the aminosulfonyl group of 1 in imparting this selectivity. Compounds were designed to investigate the effect on selectivity of the acidity of the NH group [the 7-N-methyl (compound 5) and 7-N-(p-chlorophenyl) (compound 4) derivatives of 1], the relative spatial position of the acidic hydrogen [7-(N- (methylsulfonyl)amino)-1,2,3,4-tetrahydroisoquinoline (6) and 7-((N- (methylsulfonyl)amino)methyl)-1,2,3,4-tetrahydroisoquinoline (8)], or the effect of the substitution of an acidic phenolic group for the aminosulfonyl moiety [1-(aminomethyl)-6-hydroxynaphthalene (28) and 8-hydroxy-1,2,3,4- tetrahydrobenz[h]isoquinoline (9)]. All of the compounds studied displayed lower affinity for PNMT than 1, and nine of the eleven compounds studied showed increased, rather than the desired decreased, affinity for the alpha2- adrenoceptor. Specifically, compound 4, in which the aminosulfonyl NH group is more acidic than that in 1, showed greatly reduced selectivity on account of increased alpha2-adrenoceptor affinity as compared to 1 (PNMT K(i) =- 2.6 muM, alpha2 K(i) = 6.3 muM, selectivity = 2.4). Compound 8, in which the acidic NH group is in the same region of space as that in 1, although the aminosulfonyl group is reversed with respect to the aromatic ring, showed poor PNMT affinity and modest alpha2-adrenoceptor affinity (PNMT K(i) = 330 muM, alpha2 K(i) = 18 muM, selectivity = 0.055). Compound 9, in which a phenolic group is in the same region of space as the acidic NH of 1, exhibited the best alpha2-adrenoceptor affinity of any of the compounds studied (PNMT K(i) = 0.98 muM, alpha2 K(i) = 0.078 muM, selectivity = 0.080). Results from this study suggest that the selectivity of 1 is not solely due to the presence of an acidic hydrogen on the 7-aminosulfonyl group of 1 but is likely also dependent on some other property (e.g. electron-withdrawing character) of the aminosulfonyl group.

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Tetrahydroisoquinoline – Wikipedia,
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Synthesis, evaluation and CoMFA/CoMSIA study of nitrofuranyl methyl N-heterocycles as novel antitubercular agents

A series of novel nitrofuranyl methyl N-heterocycles based on the structure of IIIM-MCD-211 were designed and synthesized. Compounds 6d, 8b and 12a show excellent activity against MTB H37Rv strain (MIC: 0.031?0.062 mug/mL) roughly comparable to INH and IIIM-MCD-211. In addition, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on the above mentioned chemical series employing comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques. The developed CoMFA and CoMSIA models display high external predictability (r2pred of 0.954 and 0.935, respectively) and good statistical robustness. More importantly, the newly designed compounds 16a and 16b (MIC: <0.016 mug/mL) based on the two models, as expected, were found to be more active than 12a and IIIM-MCD-21. Design and synthesis of more potent nitrofuranyl methyl N-heterocycles as anti-TB agents are currently in progress. Note that a catalyst decreases the activation energy for both the forward and the reverse reactions and hence accelerates both the forward and the reverse reactions.name: 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile, you can also check out more blogs about149355-52-2

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Multicyclic bis-amide MMP inhibitors

The present invention relates generally to bis-amide group containing pharmaceutical agents, and in particular, to multicyclic bis-amide MMP-13 inhibitor compounds. More particularly, the present invention provides a new class of MMP-13 inhibiting compounds, containing a pyrimidinyl bis-amide group in combination with a heterocyclic moiety, that exhibit an increased potency and solubility in relation to currently known bis-amide group containing MMP-13 inhibitors.

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Tetrahydroisoquinoline – Wikipedia,
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